Every week this new series will uncover an unreported clinical trial

Nick DeVito, Ben Goldacre

Background

The US FDA Amendments Act (FDAAA 2007) requires certain clinical trials to report their results onto ClinicalTrials.gov within one year of completion. Our FDAAA TrialsTracker shows all individual trials that breach this legal requirement. Once a week, we write about one unreported clinical trial: you can read more background here.

Trial NCT01010126

This week’s unreported trial is “A Phase 2 Trial of Temsirolimus and Bevacizumab in Patients With Endometrial, Ovarian, Hepatocellular Carcinoma, Carcinoid or Islet Cell Cancer” (NCT01010126). This single-armed interventional trial enrolled 252 adult participants across 61 locations in the US and Canada, who were then treated with temsirolimus (Torisel) and bevacizumab (Avastin). Temsirolimus is currently used in the treatment of renal cell carcinomas and bevacizumab is indicated for use in a variety of cancers. The primary outcome measures were progress free survival rate at 6 months and tumour response rate at up to 3 months. Secondary outcomes included duration of response to treatment, overall survival, time to disease progression, time to disease failure and incidence of adverse events, all up to 3 years follow-up. The study completed in March 2017.

Clinical Discussion

This trial covers two common cancer drugs and a variety of cancers in a large sample of patients. Research that assesses existing therapies for expanded use in new forms of cancer could create important new options for very large numbers of cancer patients: the table below provides US incidence and 5-year survival figures for some of the cancers covered in this trial.

Legislative Discussion

This study illustrates the importance of complete trial reporting. This trial has not reported results onto clinicaltrials.gov. However an incomplete patchwork of some results from this study has been published, across a wide variety of different articles and conference abstracts. Searches on Pubmed and Google Scholar found: 2 conference abstracts and an article on pancreatic neuroendocrine tumours (PNET); a conference abstract on epithelial ovarian cancer; and an article on hepatocellular carcinomas. There may be further publications not easily discoverable by NCT ID.

These various publications do not provide a full report of the results for this trial, either alone or in combination. They do not cover all forms of cancers described in the registry entry, and they do not cover the full sample of 252 participants enrolled: in total we could only find results on 58 ovarian cancer patients, 28 hepatocellular carcinoma patients, and 58 PNET patients (although it is unclear whether another report on 55 PNET patients is a duplicate, or describes additional patients). Furthermore, the researchers also appear to have given the NCT ID for this study in a conference abstract on PNET patients that describes results for 22 patients treated only with bevacizumab, which is not the intervention described in the protocol.

The FDA Amendments Act requires that all prespecified outcomes from all patients in every trial are reported in a simple, structured, tabular format directly onto clinicaltrials.gov within 12 months of trial completion. This is for a good reason: multiple studies have now reported that publications in conference abstracts or journal articles are overall less complete than registry results reports. As an illustration for the shortcomings of journal reports and conference abstracts: while the publications for some patients in this trial all report the prespecified primary outcomes, many secondary outcomes are missing.

In summary, despite extensive publications that appear to report results from this trial, it is clear that this trial has not been correctly reported. The incomplete journal publications and conference abstracts we did find all report promising results: this can only serve to further underscore the need for the sponsor to fully report all results from all patients in this study to ClinicalTrials.gov, as required by law.

Conclusion

This unreported trial was sponsored by the National Cancer Institute and funded under 17 separate NCI grant contracts (see “Other Study ID Numbers” section of the trial record). The PI is Dr. Henry Pitot of the Mayo Clinic. We hope the investigators will share the full results for this trial onto clinicaltrials.gov soon, as required under the FDA Amendments Act 2007.

Ben Goldacre is a doctor, author, and director of the EBM DataLab at the University of Oxford. He co-founded the AllTrials campaign for trials transparency.

Competing interests: BG has received research funding from the Laura and John Arnold Foundation, the Wellcome Trust, the Oxford Biomedical Research Centre, the NHS National Institute for Health Research School of Primary Care Research, the Health Foundation, and the World Health Organization; he also receives personal income from speaking and writing for lay audiences on the misuse of science.

Nicholas J DeVito is a researcher at the EBM Datalab at the University of Oxford.

Competing interests: ND is employed on BG’s LJAF grant.