ASCO Highlights: Trials in Progress

Oncology & Biotech NewsAugust 2011
Volume 5
Issue 8

The following is a roundup of TPS abstracts that feature trials open to patients aged >17 years with a broad range of cancer types.

The Trials in Progress Poster Session (TPS), which was held at the ASCO meeting in June and is now in its second year, is intended to stimulate discussion in the oncology community about ongoing clinical trials and to promote collaboration. The following is a roundup of TPS abstracts that feature trials open to patients aged ≥18 years with a broad range of cancer types.

Brain Cancer

Radiation therapy plus temozolomide with cilengitide or cetuximab in poor-prognosis glioblastoma

This phase II study will determine the effect of radiation therapy (RT) plus temozolomide (TMZ) combined with cilengitide or cetuximab in patients with newly diagnosed glioblastoma multiforme (GBM) with an unmethylated promoter of the O6-methylguanine-DNA-methyltransferase (MGMT) gene. An unmethylated MGMT-promoter is associated with a notoriously poor prognosis. All participants will receive postoperative RT with daily concomitant TMZ followed by adjuvant TMZ, and will then be randomized to additional treatment with either the integrin inhibitor cilengitide or the monoclonal epidermal growth factor receptor (EGFR)-targeted antibody cetuximab. The primary endpoint is the 1-year overall survival (OS). Secondary endpoints include progression-free survival (PFS) and safety. Abstract TPS134.

Sponsor: Merck identifier: NCT01044225

RO4929097 for recurrent/progressive glioblastoma

This phase II pharmacodynamic study will assess the efficacy of the oral gamma secretase inhibitor RO4929097 for the treatment of recurrent or progressive GBM and will also include biomarker assays on freshly resected GBM samples from patients receiving this agent. The primary objectives of the 60-patient study are to determine 6-month PFS in patients treated with RO4929097 and the efficiency of neurosphere generation after RO4929097 pretreatment. Abstract TPS135.

Sponsor: National Cancer Institute ID: NCT01122901

Efficacy of bevacizumab added to treatment standard in newly diagnosed glioblastoma

This phase III study will determine whether adding bevacizumab to standard-of-care treatment involving TMZ chemotherapy and radiotherapy will provide clinical benefit and a treatment advantage for patients with newly diagnosed supratentorial GBM. Coprimary endpoints are investigator-assessed PFS and OS. Secondary endpoints include independent radiology review-assessed PFS, 1- and 2-year survival rates, safety, and health-related quality of life (QOL). Neurocognitive function, signs and symptoms of disease, Karnofsky performance score, and patterns of disease progression will also be analyzed. Abstract TPS136.

Sponsor: F. Hoffmann-La Roche and Genentech ID: NCT00943826

Breast Cancer

Trastuzumab-DM1 (T-DM1) with or without pertuzumab versus trastuzumab plus a taxane for first-line treatment of metastatic breast cancer

This global phase III study will evaluate the efficacy and safety of T-DM1 with or without pertuzumab compared with trastuzumab plus either docetaxel or paclitaxel in women with human epidermal growth factor receptor 2 (HER2)-positive, progressive or recurrent locally advanced or metastatic breast cancer (MBC). T-DM1 is a unique antibody-drug conjugate that combines the antitumor activities of trastuzumab with intracellular delivery of the highly potent cytotoxic agent DM1 (derivative of maytansine). T-DM1 plus pertuzumab has demonstrated synergistic antitumor effects in preclinical models, and preliminary phase Ib/II trial results showed acceptable tolerability and promising efficacy in patients with MBC. The primary endpoint is PFS by independent review facility. Secondary endpoints include safety, overall response rate (ORR), OS, duration of response, and QOL. Thus far, 141 patients have been enrolled and the target recruitment is 1092 patients. The MARIANNE study is the first phase III study to evaluate the combination of a targeted antibody and an antibody-drug conjugate for first-line MBC. The systemic chemotherapy-sparing combination has the potential to establish a new treatment paradigm by optimizing efficacy while minimizing toxicity. Abstract TPS102.

Sponsor: F. Hoffmann-La Roche ID: NCT01120184

Metformin in early-stage breast cancer

This phase III trial will randomize women with early-stage breast cancer to treatment with metformin 850 mg by mouth twice daily or placebo twice daily for 5 years. Metformin is a biguanide used to treat type 2 diabetes that has been shown in epidemiologic, clinical, and preclinical studies to decrease breast cancer risk and improve breast cancer outcomes. The primary endpoint is invasive disease-free survival (DFS). Secondary endpoints include OS, distant DFS, breast cancer-free survival, adverse events, new diabetes, cardiovascular hospitalizations, body mass index, insulin resistance syndrome attributes by Adult Treatment Panel (ATP) III criteria, QOL, diet, and physical activity. The study plans to enroll 3582 women. Abstract TPS103.

Sponsor: National Cancer Institute ID: NCT01101438

Celecoxib for primary breast cancer

This phase III study will assess the adjuvant benefit of cyclooxygenase (COX)-2 inhibition for the treatment of primary breast cancer. Women with completely resected, unilateral breast cancer with or without prior chemotherapy and with or without prior radiotherapy will be randomized in a 2:1 ratio to either 400 mg celecoxib PO or placebo daily for 2 years. Patients will be stratified on the basis of participating center and hormone receptor status. The primary endpoint is DFS. Secondary endpoints include OS, safety, and the incidence of second primaries. A pathology substudy will examine celecoxib modulators. Abstract TPS115.

Sponsor: Pfizer ID: ISRCTN48254013

Acupuncture for aromatase inhibitorinduced arthralgia

This study will determine whether electroacupuncture will benefit women with early breast cancer who have been taking a third-generation aromatase inhibitor for at least 6 months and are experiencing a Brief Pain Inventory—Short Form (BPI-SF) score ≥3. Patients will be randomized to a 6-week course of twice-weekly treatment with real electroacupuncture or sham electroacupuncture involving the use of non-skin-penetrating needles placed at points close to the real acupoints. The primary objective of the 50-patient study is to compare the mean BPI-SF worst pain score at 6 weeks between the real and sham electroacupuncture groups. Abstract TPS120.

Sponsor: Cancer Institute NSW Research Innovation Grant

T-DM1 versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with a trastuzumabbased regimen

This phase III study will compare the safety and efficacy of T-DM1 with that of capecitabine plus lapatinib in women with HER2-positive locally advanced or MBC following prior trastuzumab-based and taxane-containing therapy. Central confirmation of HER2 status (IHC3 or FISH-positive) is required for enrollment. Eligible women will be randomized in a 1:1 ratio to either T-DM1 or lapatinib plus capecitabine until disease progression or unmanageable toxicity. The coprimary endpoints are PFS by independent review facility and OS. Secondary endpoints include objective response rate, duration of response, and patient-reported QOL and toxicity outcomes. The EMILIA trial plans to enroll 980 patients at 203 sites in 22 countries. Abstract TPS116.

Sponsor: Genentech Inc. ID: NCT00829166

Gastrointestinal Cancer

Efficacy of an ETAR antagonist added to FOLFIRI for second-line metastatic colorectal cancer

This phase II study will compare treatment with the specific endothelin A receptor (ETAR) antagonist zibotentan versus placebo combined with FOLFIRI in the second-line treatment of metastatic colorectal cancer (CRC). Patients with RECIST measurable disease, ECOG PS0-1, good end-organ function, and no previous irinotecan use are eligible for enrollment. The primary objective is to establish the antitumor activity of zibotentan with FOLFIRI as measured by PFS. Secondary objectives are to determine the toxicity and feasibility of the combination and to collect tumor and blood samples for future translational work. Abstract TPS161.

Sponsor: AstraZeneca

ISRCTN: 73199181

Cetuximab with or without brivanib for metastatic colorectal cancer

This phase III study will compare cetuximab with or without brivanib alaninate in patients with chemotherapyrefractory KRAS wild-type advanced CRC. Patients will be randomized to IV cetuximab 400 mg/m2 on day 1 followed by 250 mg/m2 weekly and then either the dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR) signaling pathways brivanib 800 mg PO daily or matched placebo. The primary endpoint is OS. Secondary endpoints include PFS, ORR, QOL, health utilities, economic evaluation, and safety. Abstract TPS163.

Sponsor: NCIC Clinical Trials Group ID: NCT00640471

Efficacy of FOLFOX with or without GDC- 0449 in patients with advanced gastric and gastroesophageal junction carcinoma

This phase II trial will examine the efficacy and safety of GDC-0449 plus a current treatment standard FOLFOX compared with FOLFOX alone as first-line therapy in patients with advanced, treatment-naïve gastroesophageal cancer. GDC-0449 is an oral smallmolecule antagonist of the hedgehog (Hh) pathway that binds to and inhibits smoothened (SMO), thereby blocking Hh signal transduction. The primary endpoint is PFS. Secondary outcomes include OS, response rate (RR), and toxicity rates. Exploratory objectives include investigation of correlations between baseline tumor Hh pathway expression and tumor genetic variation with efficacy, measurement of serum growth factor levels and shed collagen epitopes as a surrogate for response in the microenvironment, and correlation of circulating endothelial progenitor cells with response. Abstract TPS173.

Sponsor: New York Cancer Consortium ID: NCT00982592

Gemcitabine plus TH-302 versus gemcitabine alone for previously untreated advanced pancreatic cancer

This phase II study will assess the benefit of adding the hypoxia-activated prodrug TH-302, which is designed to specifically target the hypoxic microenvironment, to the standard-dose gemcitabine regimen for first-line therapy of pancreatic adenocarcinoma (PAC). A hypoxic microenvironment is believed to be a characteristic of solid tumors including PAC and is associated with resistance to chemotherapy, and combining gemcitabine with TH-302 may enable the targeting of both the normoxic and hypoxic regions of PAC. Two doses of TH-302 (240 mg/m2 or 340 mg/m2) in combination with gemcitabine will be compared with gemcitabine alone in patients with locally advanced unresectable or metastatic PAC untreated with chemotherapy. The primary efficacy endpoint is a PFS/event-free survival (EFS) comparison of the combination arms versus gemcitabine alone. Abstract TPS176.

Sponsor: Threshold Pharmaceuticals ID: NCT01144455

Genitourinary Cancer

Efficacy of a therapeutic vaccine in patients receiving sunitinib as first-line therapy for advanced/metastatic renal cell carcinoma (RCC)

This phase III study will compare IMA901 with sunitinib versus sunitinib alone in patients with advanced/metastatic clear-cell RCC who have not had prior systemic therapy for advanced disease. IMA901 is a therapeutic vaccine composed of multiple naturally presented tumor-associated peptides (TUMAPs). The primary outcome measure is OS. The study will also include a subgroup analysis of OS in patients positive for a predefined biomarker signature, PFS, and best overall objective response, as well as immunomonitoring and safety assessment. Approximately 330 patients from Europe and the United States are expected to be enrolled. Abstract TPS183.

Sponsors: Immatics and Pfizer ID: NCT01265901

Dovitinib in advanced urothelial carcinoma patients with either mutated or wild-type FGFR3

This phase II study will evaluate treatment with the oral tyrosine kinase inhibitor dovitinib in patients with advanced urothelial carcinoma who have relapsed or are refractory to conventional first-line chemotherapy. The agent will be administered at a dose of 500 mg/day in a 5-days-on/2-days-off dosing schedule, and subjects will be stratified based on the presence or absence of mutation in the FGFR gene. The primary objective is ORR. Secondary objectives include safety, PFS, OS, and disease control rate. Abstract TPS186.

Sponsor: Novartis

DN24-02 in patients with surgically resected urothelial cancer at high risk of recurrence

This phase II study will determine whether DN24-02 given as adjuvant therapy following surgical resection can prolong survival in patients who have undergone surgical resection of a primary urothelial cancer and are at high risk of recurrence. Subjects will be randomized to receive DN24-02, an autologous cellular immunotherapy product candidate targeting HER2/neu, or standard-of-care treatment and will be monitored for evidence of disease recurrence by imaging and followed for survival. Cellular and serological immune responses will be assessed at baseline and post- DN24-02 therapy. Abstract TPS187.

Sponsor: Dendreon ID: NCT01353222

MK2206 versus everolimus for refractory RCC

This phase II study will determine if patients with metastatic RCC who progress on anti-VEGFR therapy have a better outcome when treated with the selective allosteric AKT inhibitor MK2206 or the mammalian target of rapamycin inhibitor everolimus. Patients will be randomized to MK2206 or everolimus using a 2:1 ratio. The primary endpoint of the study is PFS. Secondary endpoints include safety, OS, ORR, and time-to-treatment failure (TTF). In addition, correlative studies evaluating primary tumor AKT levels, tumor virtual karyotype, and pre- versus posttherapy cytokine and angiogenesis factor levels will be examined and correlated with outcome. Abstract TPS192.

Sponsor: MD Anderson Cancer Center, Houston, TX ID: NCT01239342

Head and Neck Cancer

Concomitant chemoradiation therapy (CRT) with or without induction cisplatin/ fluorouracil plus docetaxel in locally advanced head and neck squamous cell carcinoma

This phase III study will assess the efficacy of CRT with or without induction cisplatin/fluorouracil plus docetaxel in patients with locally advanced squamous cell carcinoma unresectable stage III-IVMO of the oral cavity, oropharynx, or hypopharynx. An ECOG PS 0-1, measurable disease by RECIST, and adequate organ function are required for inclusion. Primary endpoints are the comparison of 3-year OS between induction versus no induction and the incidence of grade 3 or 4 in-field toxicity between CRT and radiotherapy/ cetuximab. The study aims to recruit 420 patients. Abstract TPS196.

EGFR-antibody combined with adjuvant CRT for high-risk head and neck squamous cell carcinoma

This open-label phase III randomized trial will investigate whether the addition of the anti-EGFR antibody panitumumab to adjuvant CRT significantly prolongs DFS in patients with head and neck cancer who are at high risk of recurrence. Patients with close resection margins (<5 mm) or extracapsular extension will be randomized to receive 7 weeks of concomitant CRT (3 cycles of cisplatin or 2 cycles of cisplatin and 5-fluorouracil with 66 Gy radiotherapy), /— weekly panitumumab 2.5 mg/kg. DFS at 5 years is roughly 40% after standard adjuvant CRT in patients with resected head and neck squamous cell carcinoma at high risk of recurrence. Abstract TPS197.

Sponsor: EORTC ID: EORTC 22071-24071

Hematologic Cancer

Induction and consolidation chemotherapy combined with midostaurin in patients with FLT3 mutated acute myeloid leukemia

This phase III study will evaluate induction (daunorubicin/ cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with the FLT3 inhibitor midostaurin or placebo in treatment-naïve patients with FLT3-mutated acute myeloid leukemia (AML). Subjects will be stratified at baseline using molecular screening of FLT3 mutation and internal tandem duplications allelic ratio. The primary endpoint is OS not censored for stem cell transplantation, and secondary endpoints include EFS and complete response rate (CRR). Abstract TPS199.

Sponsor: Novartis ID: NCT00651261

Vosaroxin or placebo with cytarabine for relapsed or refractory acute myeloid leukemia

This phase III study will compare the efficacy and safety of vosaroxin in combination with cytarabine versus placebo combined with cytarabine in patients with first relapsed or primary refractory AML. Vosaroxin is an investigational anticancer quinolone derivative. Study participants will be randomized to receive either vosaroxin on days 1 and 4 plus cytarabine daily for 5 days, or placebo combined with cytarabine. The primary endpoint is OS, with the complete response rate as a secondary outcome measure. Abstract TPS201.

Sponsor: Sunesis Pharmaceuticals ID: NCT01191801

INC424 or placebo in polycythemia vera resistant to or intolerant of hydroxyurea

This phase III trial will compare the efficacy and safety of INC424 to best available therapy (BAT) in adult patients with polycythemia vera that is resistant to or intolerant of hydroxyurea, which is an established first-line agent for cytoreduction. INC424 is a potent and selective inhibitor of janus-associated kinase (JAK)1 and JAK2. The primary efficacy endpoints, assessed after 32 weeks of treatment, include phlebotomy independence and a ≥35% reduction in spleen volume as measured by imaging. Patients randomized to BAT may be eligible to cross over to receive INC424 after week 32, and all patients will be treated for 80 weeks to assess safety and response durability. Abstract TPS203.

Sponsor: Novartis ID: NCT01243944

Temsirolimus dosing in relapsed, refractory mantle cell lymphoma

This phase IV study will evaluate whether temsirolomus treatment is as effective in patients with relapsed, refractory mantle cell lymphoma when the agent is administered without the 175-mg starting dose that was used in the phase III trial. In the phase III study, patients treated with IV 175 mg for the first 3 weeks followed by 75 mg weekly (175/75) had significantly longer PFS than patients receiving the investigators’ choice of therapy (HR = 0.44; P = .0009) but also had a higher incidence of adverse events relative to investigator’s choice and to that observed with temsirolimus at lower doses. A total of 100 participants will be randomized to receive temsirolimus 175/75 or 75 mg weekly and will be stratified by histologic subtype. The primary endpoint is PFS based on independent tumor assessments. Abstract TPS222.

Sponsor: Pfizer ID: NCT01180049

Efficacy of carfilzomib added to treatment standard in relapsed multiple myelomaThis phase III study will compare the selective, irreversible epoxyketone proteasome inhibitor carfilzomib on top of a treatment standard lenalidomide and dexamethasone to lenalidomide and dexamethasone without carfilzomib in patients with relapsed multiple myeloma. Randomization will be stratified by β2 microglobulin levels, prior bortezomib, and prior lenalidomide. Patients will receive the treatment determined by randomization in 28-day cycles until disease progression or unacceptable toxicity, whichever occurs first. The primary endpoint is PFS. Secondary endpoints include OS, ORR, disease control rate, duration of response, and safety. Abstract TPS225.

Sponsor: Onyx Therapeutics, Inc. ID: NCT01080391

Lung Cancer

Adjuvant erlotinib in EGFR-mutant earlystage lung cancer and confirmed EGFR mutations

This phase II study will examine whether genotypedirected adjuvant TKI therapy with erlotinib is effective in decreasing recurrence rates in patients with resected, early-stage non—small cell lung cancer (NSCLC) and confirmed activating EGFR mutations. Participants will be treated with erlotinib, 150 mg/d, for a total of 2 years, with surveillance scans every 3 months. The primary endpoint is DFS at 2 years. Secondary endpoints include safety and tolerability of adjuvant erlotinib, median DFS, and OS. Abstract TPS209.

Sponsor: Genentech ID: NCT00567359

MAGE-A3 antigen-specific cancer immunotherapy as adjuvant therapy in patients with completely resected stage IB-IIIA non—small cell lung cancer

This phase III study will test the efficacy of MAGE-A3 antigen-specific cancer immunotherapeutic (ASCI) in preventing cancer relapse, when given after tumor resection in patients with MAGE-A3-positive stages IB, II, and IIIA NSCLC. About one-third of NSCLC tumors are MAGE-A3-positive. Coprimary endpoints are DFS in the overall population and DFS in the population that has not received adjuvant chemotherapy prior to the study treatment. Secondary endpoints include OS, safety health-related QOL, and validation of a predictive gene signature associated with clinical benefit of the MAGEA3 ASCI. Abstract TPS210.

Sponsor: GlaxoSmithKline ID: NCT00480025

Erlotinib with or without fulvestrant in previously treated advanced non—small cell lung cancer

This phase II study will determine whether fulvestrant adds to the antitumor efficacy of erlotinib in men and pre- and postmenopausal women with advanced NSCLC who have had at least 1 prior chemotherapy regimen. The primary endpoint is the response rate, and secondary endpoints include the correlation between clinical response and expression of ERα, ERβ, EGF/HER1 receptor, and HER2/neu biomarkers. The study plans to recruit 102 patients. Abstract TPS216.

Sponsor: AstraZeneca, Genentech, Stiles Program

Gemcitabine/carboplatin with or without iniparib for advanced squamous NSCLC

This phase III study will compare the gemcitabine/ carboplatin doublet alone or in combination with the poly-(ADP ribose) polymerase (PARP) inhibitor iniparib in patients with previously untreated stage IV (M1a and M1b) squamous NSCLC. Patients with disseminated metastases or malignant pleural or pericardial effusions are eligible for inclusion. The primary endpoint is OS. Patients may have had carboplatin in the adjuvant setting for early-stage disease; however, prior treatment with gemcitabine or iniparib is not allowed. The study has a target enrollment of 825 patients. Abstract TPS220.

Sponsor: Sanofi-Aventis ID: NCT01082549

Melanoma/Skin Cancers

Nilotinib in patients with KIT-mutated advanced acral and mucosal melanoma (NICAM)

This 2-stage phase II study will evaluate the efficacy of nilotinib in KIT-mutated advanced mucosal and acral melanoma. The primary endpoint is PFS at 6 months. Secondary endpoints include response rate at 12 weeks, OS, treatment toxicity, correlation between the response to nilotinib and KIT genotype, and KIT gene copy number. KIT mutations occur in about 20% of acral and mucosal melanomas, and KIT-mutated melanomas have been found to respond to treatment with KIT inhibitors. The TKI nilotinib has shown clinical efficacy at well-tolerated doses in patients with advanced KIT-mutated gastrointestinal stromal tumor (GIST). Abstract TPS229.

Sponsor: Royal Marsden NHS Foundation Trust, London, UK

Ipilimumab and fotemustine for metastatic melanoma

This phase II study will examine the clinical and immunologic efficacy of the combination of ipilimumab and fotemustine in patients with unresectable stage III or IV cutaneous melanoma with or without brain metastases. The primary endpoint is the immuneresponse disease control rate using immune-related response criteria. Secondary endpoints include safety, tolerability, and feasibility of treatment; ORR; RR; duration of response; PFS; brain-PFS; 1- and 2- year survival rates; and OS. The study aims to recruit 84 patients. Abstract TPS230.

Sponsor: Bristol-Myers Squibb

Gene signature for predicting clinical benefit from immunotherapy in unresected metastatic cutaneous melanoma

The aim of this phase II study is to prospectively validate a gene signature (GS) as a predictive biomarker of the clinical outcome of the MAGE-A3 ASCI in patients with histologically proven, measurable MAGEA3 metastatic cutaneous melanoma. The MAGE-A3 ASCI combines the tumor-specific antigen MAGE-A3, delivered as a recombinant protein, with the immunostimulant AS15. Study participants will receive a maximum of 24 doses of MAGE-A3 ASCI by IM injection over 48 months. The primary endpoint is 1-year OS in the GS population. Secondary endpoints include 1-year OS in the global and GS populations, as well as the clinical response rate, PFS, and median OS in all 3 populations. Abstract TPS231.

Sponsor: GlaxoSmithKline ID: NCT00942162

MAGE-A3 immunotherapy as adjuvant treatment in stage III melanoma

This phase III study will randomize (in a 2:1 ratio) patients with advanced melanoma to MAGE-A3 ASCI or placebo. Patients are eligible provided they have cutaneous melanoma expressing MAGE-A3 with histologically proven macroscopic nodal disease (AJCC Stage IIIB-C) and complete surgical resection of all tumors. The primary endpoint is DFS in the overall patient population. Secondary endpoints include OS, health-related QOL (EQ-5D), and a previously defined gene signature associated with MAGE-A3 ASCI benefit. A maximum of 13 doses will be administered by IM injection over 27 months. Abstract TPS232.

Sponsor: GlaxoSmithKline

ClinicalTrials.Gov ID: NCT00086866

Prostate Cancer

Custirsen in metastatic castrationresistant prostate cancer (CRPC)

This phase III study will determine whether adding the second-generation antisense oligonucleotide custirsen to standard first-line docetaxel/prednisone treatment slows tumor progression and enhances survival beyond docetaxel/prednisone alone in metastatic CRPC. A total of 800 chemotherapy-naïve patients will receive either docetaxel/prednisone every 21 days or docetaxel/prednisone plus custirsen (640 mg IV weekly) until disease progression or unacceptable toxicity. The primary outcome measure is OS. Additional analyses include PFS at day 140 and day 225, safety of custirsen combined with docetaxel/ prednisone, PSA measurements, and the association of efficacy measures with reduction of serum clusterin levels. Abstract TPS180.

Sponsors: Teva and OncoGenex ID: NCT01188187

Ipilimumab or placebo after radiotherapy in advanced prostate cancer

This phase III study will randomize men with advanced prostate cancer to bone-directed radiotherapy followed by either the anticytotoxic T-lymphocyte antigen-4 antibody ipilimumab or placebo as induction therapy. Patients are eligible if they have CRPC that has progressed during or after docetaxel treatment. The primary endpoint of the 800-patient study is OS. Secondary endpoints include TTF, objective response, PSA response/ kinetics, pain palliation, and safety. Abstract TPS181.

Sponsor: Bristol-Myers Squibb identifier: NCT00861614

TAK-700 plus prednisone for chemotherapy-naïve metastatic CRPC

This phase III study will compare treatment with the investigational selective, oral, nonsteroidal androgen synthesis inhibitor TAK-700 plus prednisone versus placebo plus prednisone in patients with metastatic CRPC (mCRPC) who have not received prior chemotherapy. The main inclusion criteria for the 1454-patient study are radiographically documented mCRPC, surgical castration or the use of an agent for medical castration with baseline testosterone <50 ng/dL, and evidence of disease progression based on X-ray or an increasing PSA value. The primary outcomes are OS and radiographic PFS. Secondary outcomes include the PSA response rate (decrease by ≥50%) at 12 weeks, change in circulating tumor cell numbers, and time to pain progression. Abstract TPS184.

Sponsor: Millennium Pharmaceuticals, Inc. NCT01193244

Sipuleucel%u2011T in metastatic androgendependent prostate cancer

This phase III study will test the efficacy of the therapeutic cancer vaccine sipuleucel-T in men with metastatic androgen-dependent prostate cancer (mADPC). Patients will receive standard treatment involving androgen deprivation therapy (ADT) to achieve castration-level testosterone and will then be randomized to receive sipuleucel-T or continue on ADT alone. The primary endpoint of the 1684-patient trial is OS. Secondary endpoints are safety, QOL, time to castration resistance, and chemotherapy- free survival. Abstract TPS188.

Sponsor: Dendreon

Supportive Care

Sotatercept for chemotherapy-induced anemia in advanced lung cancer

This phase II/III study will examine treatment with the activin antagonist sotatercept in patients with metastatic NSCLC treated with first-line platinumbased chemotherapy. The analysis will include a single- blind, randomized, phase IIA, dose-ranging study (part 1) of sotatercept therapy followed by a phase IIB/III, double-blind, randomized, placebo-controlled study (part 2). The primary outcome measure is hematopoietic response. Roughly 90 patients are expected to participate. Abstract TPS235.

Sponsor: Celgene ID: NCT01284348

Methylnaltrexone for opioid-induced constipation in cancer patients

This phase II trial will evaluate the efficacy of methylnaltrexone bromide for relieving opioidinduced constipation (OIC) in cancer patients with life expectancy ≥6 months. Methylnaltrexone, a peripherally acting antagonist of the mu-opioid receptor, was recently approved as an OIC treatment in patients with advanced disease receiving palliative care. The primary endpoint is a rescuefree laxation ≤4 hours after the dose. A single dose of methylnaltrexone will be administered subcutaneously to eligible patients, and efficacy and adverse events will be evaluated for 48 hours. Patients will complete questionnaires on laxation (frequency, consistency, and difficulty), constipation (severity and distress), pain score, symptoms of opioid withdrawal, and satisfaction with the response at 4, 24, and 48 hours following the dose. Abstract TPS236.

Sponsor: University of Vermont College of Medicine in Burlington ID: NCT01004393

Testosterone replacement for fatigue in male hypogonadic advanced cancer patients

This phase III study will assess the efficacy of testosterone replacement therapy in men with metastatic or locally recurrent cancer who have experienced fatigue every day for the last 2 weeks and have an Edmonton Symptom Assessment System (ESAS) fatigue score >3 and bioavailable testosterone >70 ng/dL. Patients will be randomized to gluteal injections of 150- or 200-mg weight-based testosterone enanthate or placebo at baseline and on days 15, 29, 43, and 57. The primary outcome measure is the Functional Assessment of Cancer Therapy-Fatigue subscale (FACT-F) at day 29 ( /— 3 days). The study will also examine the effect of testosterone replacement on depression, low sexual desire, and anorexia/ cachexia, as well as functional outcomes, including spontaneous activity, strength, and endurance. Abstract TPS238.

Sponsor: MD Anderson Cancer Center in Houston, TX ID: NCT00965341

12-weekly intravenous bisphosphonate therapy in women with low-risk bone metastases from breast cancer

This study will examine whether IV bisphosphonates (BPs) can be safely given to breast cancer patients with biochemically defined low-risk bone metastases every 12 weeks. Most patients currently receive an IV BP every 3 to 4 weeks regardless of their individual risk for a skeletal-related event (SRE). This one-size-fits-all strategy exposes individuals who are at a relatively low risk of SREs to the financial and QOL burden of multiple clinic visits for treatments, along with an increased risk of drug toxicity. The primary aim of the study is to demonstrate that the administration of IV BP every 12 weeks is sufficient to maintain biochemical stability for 1 year. The palliative benefit of 12-weekly IV BP therapy as reflected by occurrence of SREs, analgesic use, and self-reported pain (using validated pain measures) will also be evaluated. Abstract TPS242.

Sponsors: McGill University, Segal Cancer Centre, and Jewish General Hospital, Montreal, Canada

Denosumab for hypercalcemia of malignancy in patients who are refractory to IV bisphosphonates

This phase II study will evaluate treatment with the RANK ligand inhibitor denosumab in patients with hypercalcemia of malignancy who have not responded to recent IV bisphosphonate therapy. Patients with confirmed cancer and IV BP treatment over the past 7 to 30 days and corrected serum calcium (CSC) levels >12.5 mg/dL will receive denosumab 120 mg SC monthly with a loading dose on study days 8 and 15. The primary endpoint is the proportion of patients with a response in CSC (defined as CSC ≤11.5 mg/dL by day 10 of treatment). Secondary endpoints include complete response (defined as CSC ≤10.8 mg/dL by day 10 of treatment), response by visit, time to response, response duration, and safety. Abstract TPS245.

Sponsor: Amgen Inc. ID: NCT00896454

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