The Trials in Progress section is intended to stimulate discussion about ongoing clinical trials and to promote collaboration across the oncology community. Each month, OBTN will present summaries of ongoing research in a broad range of cancer types. This month’s collection highlights trials presented at the 2011 American Society of Clinical Oncology Meeting [J Clin Oncol.
Evaluating role of CER into RxPONDER study
The Center for Comparative Effectiveness Research in Cancer Genomics (CANCERGEN) is designed to integrate comparative effectiveness research (CER) into prospective SWOG (formerly Southwestern Oncology Group) trials. This is being applied to the RxPONDER study, a prospective randomized trial evaluating the role of Oncotype DX-guided therapy compared to usual care among women with lymph node-positive, endocrineresponsive breast cancer. Women with endocrineresponsive HER2-negative breast cancer involving 1 to 3 lymph nodes are invited to receive a test based on the 21-gene assay. Those with a recurrence score (RS) ≤25 are randomized into chemotherapy followed by endocrine therapy or endocrine therapy alone. In addition to RxPONDER primary endpoints, economic modeling and trial data will be used to assess the cost effectiveness of management using RS compared to usual care. Abstract TPS101.Sponsor: SWOG
ClinicalTrials.gov Identifier: NCT01272037Dual IGF-1R/IR inhibitor with or without letrozole in aromatase inhibitor-resistant breast cancer
Evidence shows that insulin-like growth factor (IGF) pathway signaling contributes to tamoxifen resistance, and blocking that signaling may reverse resistance to endocrine therapy. A phase II trial is underway to investigate the combination of BMS-754807, an oral IGF-1R/insulin receptor (IR) kinase inhibitor, and 2.5 mg letrozole or single-agent BMS-754807 in patients with locally advanced or metastatic, estrogen receptor-positive, nonsteroidal aromatase inhibitorresistant breast cancer. The primary objective is 6-month progression-free survival (PFS) for the combination. Secondary endpoints include response rate, safety profile, and 6-month treatment failure rate for BMS-754807 and for the combination. Abstract TPS111.Sponsor: Bristol-Myers Squibb and National Institutes of Health
ClinicalTrials.gov Identifier: NCT01225172
PARP inhibitor for use in patients with metastatic pancreatic cancer
Poly (ADP-ribose) polymerase (PARP) inhibitors are sensitizing agents for DNA-damaging chemotherapy agents like platinum analogs, and the effects are magnified when cancer cells harbor DNA repair enzyme defects, including BRCA2, FANCD2, PTEN, and others. An open-label phase I/II study has been initiated to study a PARP inhibitor called ABT-888 in patients with metastatic, unresectable pancreatic cancer who have adequate performance status and normal hepatic and renal function. The primary endpoint is to achieve objective response rate (ORR). Secondary endpoints include disease control rate, PFS, and overall survival (OS). Abstract TPS170.Second-line therapy with PIE in metastatic colorectal cancer with KRAS wild-type
Activation of the EGFR results in cell proliferation and survival. Mutations in the KRAS
gene result in an active protein that is independent of EGFR and is not inhibited by anti-EGFR monoclonal antibodies. Aberrations in other downstream signaling also confer resistance to EGFR antagonists. Inhibition of the mammalian target of rapamycin (mTOR), a key downstream regulatory protein, in addition to the blockage of EGRF, may cause a more profound antitumor effect. A study is enrolling patients with metastatic colorectal cancer that is KRAS wild-type. Patients received panitumumab and irinotecan through IV every 2 weeks, with everolimus administered orally throughout the 14-day cycle. Abstract TPS162.Sponsor: The Queen Elizabeth Hospital, Amgen, Novartis
ClinicalTrials.gov Identifier: NCT01139138
Vascular-disruption agent in combination with everolimus for progressive renal cell carcinoma
Treatment of progressive metastatic renal cell carcinoma (mRCC) for patients who are refractory to tyrosine kinase inhibitors (TKIs) with everolimus following previous sunitinib and/or sorafenib has been associated with significant improvement in PFS. Vascular-disruption agents (VDAs) may provide potential enhancement in efficacy by acting to damage tumor endothelial cells, leading to an occlusion of blood flow and subsequent necrosis. BNC105P is a VDA that destabilizes tubulin polymers leading to a direct antiproliferative action on cancer cells. The phase I component of this study will investigate BNC105P at 4 dose levels and everolimus in the approved dosage. The phase II study will compare everolimus with BNC105P to everolimus alone. Abstract TPS194.