New Trials in Colorectal Cancer: Could Your Patient Benefit?

Several clinical trials in colorectal cancer have started recently. Perhaps one of your patients is eligible to take part.

Lynch syndrome at least 6 months from any cancer-directed treatment. Adult patients with this inherited cancer syndrome are eligible for a National Cancer Institute randomized controlled phase 2b study. The trial will evaluate whether a trivalent adenovirus-5 vaccine (TriAd5) along with the IL-15 superagonist nogapendekin alfa inbakicept (N803) can stave off the development of colorectal neoplasms. Lynch syndrome carries a 15% to 80% lifetime risk for colorectal cancer.

In the trial, one group of participants will receive subcutaneous injections of the TriAd5-N803 combination at baseline and at 4, 8, and 52 weeks thereafter. The other group will receive placebo injections on the same schedule. Everyone will undergo standard-of-care colonoscopy with biopsy at baseline and at the 1- and 2-year marks. Centers in Arizona, Illinois, Kansas, Michigan, and Texas started recruiting 186 participants in May 2023. Sites in California, Colorado, Massachusetts, Minnesota, Ohio, Utah, and Puerto Rico are also planned. Incidence of adenomas, advanced adenomas, and colon cancer is the primary endpoint. Quality of life (QoL) is a secondary endpoint. and overall survival will not be measured. More details available at clinicaltrials.gov

“Interventions to reduce the risk of cancer in patients with Lynch syndrome are urgently sought by people with the syndrome, many of whom have lost relatives to cancer, and by their medical and family caregivers,” said Richard Goldberg, MD, professor emeritus at the West Virginia University Cancer Institute.

BRAF-mutated stage IIB-III colon cancer. Adults with this cancer who have undergone standard surgery and chemotherapy are sought for a randomized, open-label, phase 2/3 trial to determine whether encorafenib plus cetuximab can slow or prevent disease recurrence. The combination is currently indicated for the treatment of adults with metastatic colorectal cancer that has a BRAF V600E mutation.

In the trial, one group of participants will receive usual care (observation) after surgery and chemotherapy. A second group will take daily capsules of encorafenib and receive weekly intravenous (IV) infusions of cetuximab.

The primary outcomes in the phase 2 part of the study include circulating-tumor DNA (ctDNA) clearance or ctDNA recurrence-free survival 6 months after randomization among patients with detectable ctDNA status at randomization. Disease-free survival, assessed up to 6 years after randomization, is the primary outcome in phase 3. Overall survival is a secondary outcome. QoL measures beyond fatigue will not be tracked. The trial, which began enrolling in May 2023 in nine states, is seeking to enroll 394 participants. More details available at clinicaltrials.gov

“Studies in patients with advanced colorectal cancer harboring BRAF mutations have shown favorable responses to [this] combination,” Goldberg said. The high recurrence rate associated with BRAF mutations make this an “important line of inquiry,” he added.

Colorectal cancer with at least one measurable tumor. Adults with this diagnosis can join an open-label phase 2 study evaluating a new diagnostic imaging agent, ⁸⁹Zr-girentuximab. This radiolabeled monoclonal antibody from Telix Pharmaceuticals targets carbonic anhydrase IX (CAIX), an enzyme that regulates cell proliferation and is highly expressed in many tumor types.

Participants will receive IV ⁸⁹Zr-girentuximab, followed by a PET or CT scan approximately 5 days later. ⁸⁹Zr-girentuximab uptake by the tumors is the primary outcome; safety measures are the secondary outcomes. Overall survival and QoL will not be tracked. Sites in Virginia and Washington opened their doors in June 2023 seeking 100 participants with a range of solid tumor types. More details available at clinicaltrials.gov

“Enrollment in this trial will not directly benefit the study subjects, as this study is evaluating a new diagnostic rather than a therapeutic strategy,” said Goldberg.

Familial adenomatous polyposis with duodenum or residual colon/rectum/pouch involvement. Individuals with this rare condition who have undergone colectomy or subtotal colectomy can enroll in an open-label phase 2 trial to see whether REC-4881 reduces the remaining polyps. Familial adenomatous polyposis predisposes people to develop GI polyps that frequently transform into GI cancers. There are currently no approved drugs for such patients.

REC-4881, developed by Recursion, inhibits the MEK pathway, a prime mover in cancer cell biology. All participants will take daily capsules of REC-4881, and investigators will assess adverse events for up to 30 weeks. Centers across Arizona, California, Florida, Louisiana, Pennsylvania, and Utah started recruiting 37 participants for the trial in July 2023. The primary outcomes are safety and polyp burden; overall survival and QoL will not be tracked. More details are available at clinicaltrials.gov

“While some benefit to an individual patient is possible, the main emphasis of the study is safety and drug tolerance,” Goldberg said.

Untreated T4N0 or stage III defective mismatch repair/microsatellite instability high (dMMR/MSI-H) colon cancer. Adults facing this clinical scenario who are eligible for surgery can join an open-label, randomized phase 3 study examining the effectiveness of the PD-1 inhibitor dostarlimab in the adjuvant setting. Dostarlimab is currently indicated for the treatment of dMMR recurrent or advanced endometrial cancer and other solid tumors.

In this study, one group of individuals will receive IV infusions of dostarlimab before and after their surgeries every 3 weeks for the first 4 weeks followed by every 6 weeks. A second group will receive standard of care, either expectant observation or FOLFOX/CAPEOX. Centers in Canada began welcoming the planned 711 trial participants in August 2023; trial sites across 14 US states, the District of Columbia, and 21 other countries are gearing up. The primary outcome is event-free survival; overall survival over 5 years is a secondary outcome. QoL will not be measured. More details are available at clinicaltrials.gov

“Dostarlimab has shown striking activity in a small study of patients with rectal cancers that manifested deficient mismatch repair,” Goldberg said. “The hope is that similar findings will be observed in subjects randomly assigned to the dostarlimab arm of this trial.”

Stage I-III colorectal cancer diagnosed in past 12 months. Adults with this type of cancer who have completed standard treatment may be eligible for a randomized, controlled phase 2 study evaluating a new personalized self-management training program called RISE (Re-Invent, Integrate, Strengthen, Expand). Typically, cancer centers offer standardized self-management training after treatment. The approach being tested here, however, is individualized and will include motivational interviewing, cognitive-behavioral therapy, collaborative problem solving, and accountability.

Over a 6-week period, one group of participants will participate in RISE while the other will attend a standardized program. Cedars-Sinai Medical Center in Los Angeles started recruiting 120 participants in October 2023. The primary outcome is program adherence, determined on the basis of measures such as body composition and physical activity. QoL is a secondary outcome, and overall survival will not be measured. More details are available at clinicaltrials.gov

“There is evidence that lifestyle modification in this setting can reduce the risk of recurrence or a second cancer,” said Goldberg.

All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

Goldberg was not involved with any of the trials presented here.

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