What if a negative study had been made available through a secure online registry where patients could sign up, with the assistance of their own oncologists?
This commentary addresses a strategy that has yet to gain traction within the oncology research community, but that may offer the potential to substantially expand the opportunities for highly relevant clinical research and dramatically decrease the time required for study results to be obtained and subsequently reported.
The suggestion discussed below focuses on permitting patients within the community who are interested in participating in molecular diagnostic-based clinical research involving novel targeted antineoplastics to be included in a clinical trial (investigator or industry-sponsored) but with all treatment and follow-up undertaken by the patient’s own oncologist.
The backdrop for this discussion is a provocative—but quite negative—clinical trial that involved a group of patients with breast cancer who were treated with the antineoplastic agent dasatinib based on the presence of a unique gene-signature within the individual’s tumor.1 The clinical trial recruited patients with breast cancer with a reasonable performance status (Zubrod scale ≤2) who had received an unlimited number of prior chemotherapy regimens. A biopsy (fine-needle aspiration preferred) was required for the performance of the intended molecular analysis. Other study requirements included acceptable organ function and the absence of pleural or pericardial effusions, or evidence of cardiac dysfunction. Further, treatment with dasatinib on the trial was only to be administered if one of the three proposed gene signatures was present in the cancer.
A total of 97 patients were included in this study, of which 93 underwent a biopsy. Based on the molecular findings, 30 patients were eligible for treatment on the trial (8, 9, and 13 in the three study arms). Only a single patient experienced “stable disease for more than 300 days.”1 The investigators appropriately concluded this study failed to demonstrate the clinical utility of the proposed gene predictive signatures.
What can we learn from this experience that is relevant to the specific question of community-based involvement in studies such as this one? First, it should be noted that this study employed a commercially available antineoplastic agent (dasatinib) and a large percentage of nonacademic oncologists would be familiar with this drug. Second, this trial required 3 years to complete accrual, with the investigators noting that accrual was particularly slow during the final year (10 patients in 10 months) “as the limited antitumor activity and modest biopsy positivity rates became apparent.”1 Finally, the published report did not appear in the peer-reviewed literature for an additional 2 years.
Recruiting Through an Online Registry
So, here is the proposal: What if this study had been made available to a far wider group of patients with breast cancer through a secure online registry where patients could enroll, with the support and assistance of their own oncologists (ensuring eligibility, acceptable comorbidity, and tumor location for the mandated biopsy)? The biopsy could have been performed locally, appropriately prepared with pathology review to ensure the presence for viable cancer, and sent either to the academic CLIA-certified laboratory or to a commercial molecular laboratory (assuming the required assay results could be obtained through this mechanism).
If the patient’s tumor was found to contain one of the necessary gene signatures, treatment could be initiated (assuming insurance approval or an alternative mechanism to obtain the required agent), with necessary monitoring for efficacy and safety performed locally. All relevant clinical results would be securely posted online (ensuring strict adherence to HIPPA guidelines). Further, imaging studies could also be posed with subsequent central review, if considered necessary.
It is quite reasonable to assume that there would be considerable interest among patients with cancer in participating in such novel studies, if they are based on rational preclinical or clinical observations and utilize a previously well-studied and commercially available antineoplastic agent. An additional major attraction would be the fact that the patient would not have to travel far from home, interfering with normal activities of daily living for both herself/himself and quite likely a caregiver (eg, spouse, child of an older patient, other relative).
In the study discussed in this commentary, a period of 3 years was required to find 30 appropriate patients for treatment on the trial. Considering the size of the breast cancer population in the United States, this study’s clear rationale, use of an established commercially available antineoplastic, and the broad eligibility criteria (eg, no limitation on the number of prior chemotherapy regimens), it is reasonable to suggest that a similar number of patients both interested and eligible for the trial could have been found within a maximum of several months from the time it was officially opened.
And, assuming the results were again “negative” (regarding objective responses), these definitive data would have been available for viewing by the academic community and prospective patients (following confirmation of the protocol-defined endpoint of futility) within a very short period of time, possibly even 6 months from trial activation.
If this study had been undertaken through the hypothetical process described above, the actual 5-year timeline to report an important negative result could have been reduced to 6 months, or less. Of course, the reporting of positive study results could be similarly expedited.
Finally, the number of such innovative clinical trials that could be ongoing on a national level at the same time theoretically could increase substantially, rather dramatically accelerating research productivity for the benefit of patients everywhere.
Maurie Markman, MD, editor-in-chief, is president of Medicine & Science at Cancer Treatment Centers of America, and clinical professor of Medicine at Drexel University College of Medicine. email@example.com.
Pusztai L, Moulder S, Altan M, et al. Gene signature-guided dasatinib therapy in metastatic breast cancer [published online August 29, 2014]. Clin Cancer Res. 2014;20(20):5265-5271.