Several new clinical trials in colorectal cancer started recruiting in recent months. Maybe one of your patients could benefit from taking part.
HER2+ metastatic and/or unresectable colorectal cancer. Patients in this position who have not received anti-HER2 therapy or any systemic therapy in the metastatic setting may be interested in a randomized, open-label, phase 3 clinical trial to find out whether a tucatinib (Tukysa)-based combination works better than standard of care. For up to 3 years or until disease progression or death, whichever occurs first, one group of participants will take tucatinib tablets twice daily. They will also receive intravenous (IV) infusions of trastuzumab (Herceptin) every 3 weeks along with standard chemotherapy every 2 weeks. People in the standard-of-care arm will receive IV chemotherapy every 2 weeks, either alone or in combination with IV bevacizumab (Avastin) ― also every 2 weeks ― or IV cetuximab (Erbitux) weekly. Study centers in 15 US states and six countries started recruiting 400 participants in October 2022. Progression-free survival (PFS) is the primary endpoint; overall survival (OS) over 6 years and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov
When ask to comment on this study, Richard Goldberg, MD, professor emeritus at West Virginia University Cancer Institute, said: "Combining two drugs that target EGFR and delivering them with chemotherapy in second-line phase 2 studies has shown promise for the subset of colorectal cancers that overexpress EGFR.... This important first-line phase 3 trial in this cohort of patients is a natural next step to evaluate the strategy in patients previously untreated for their metastatic disease and has the potential to change the standard of care if positive."
Colorectal cancer with cachexia. People in this clinical scenario who are not receiving tubal or parenteral nutrition are eligible to participate in a randomized, double-blind, phase 2 clinical trial testing the investigational agent ponsegromab (from Pfizer) for cachexia. There are currently no approved drugs specifically for cachexia. The mechanisms involved are poorly understood, although cachexia is correlated with elevation in circulating growth-differentiation factor 15 (GDF15). Ponsegromab is a humanized anti-GDF15 antibody inhibitor that has shown some preclinical effectiveness. Participants will receive three subcutaneous injections of either placebo or ponsegromab 4 weeks apart over 12 weeks. All participants will then have the opportunity to receive ponsegromab injections for up to a year in an open-label setting. Sites in California, Texas, Washington, and Japan started recruiting in November 2022. The investigators are aiming to recruit 168 participants among individuals with three different solid cancers. Research centers in four more US states and Taiwan are planned. Change in body weight is the primary endpoint, and QoL is a secondary endpoint. OS will not be tracked. More details at clinicaltrials.gov
Goldberg commented: "Cachexia remains a vexing problem in patients with many types of malignancies, although in colorectal cancer it is commonly related to peritoneal disease and other mechanical cancer related issues ― a circumstance that may complicate the interpretations of the findings in this study."
Chemotherapy-resistant nonmucinous peritoneal carcinomatosis of colorectal primary histology. Adult patients with this diagnosis whose disease is too widespread for surgery are being recruited for an open-label phase 2 National Cancer Institute study to determine whether a combination of nilotinib (Tasigna) plus paclitaxel (Taxol and others) can shrink the tumors enough for surgery. For up to 1 year, depending on the results, participants will take nilotinib capsules twice daily and will receive two doses of IV paclitaxel every 3 weeks. In addition, for at least the first 9 weeks, they will receive one dose of paclitaxel every 3 weeks via an intraperitoneal port. Results will be measured at least twice during the trial by laparoscopy and CT. The study opened in October 2022 at the National Institutes of Health Clinical Center in Bethesda, Maryland. The investigators plan to recruit 70 participants with a range of cancers. The primary outcome is the rate of downstaging of peritoneal disease burden to a resectable state. OS and QoL are secondary outcomes. More details at clinicaltrials.gov
Goldberg commented: "This exploratory study uses paclitaxel, a drug with little activity in patients with peritoneal spreading of appendiceal and colorectal cancers, as a partner for nilotinib. Using paclitaxel as a partner chemotherapy makes more sense as a strategy for treating ovarian cancer patients whose disease is often responsive to taxane treatment than it does for patients with bowel cancers."
Refractory metastatic colorectal cancer. Adults in this situation who do not have microsatellite-instability high (MSI-H) or deficient mismatch repair (dMMR) status can join a randomized, open-label, phase 2 study testing two investigational immuno-oncology drugs, botensilimab and blastilimab (both from Agenus). For up to 2 years, participants will receive either standard of care or an IV botensilimab regimen. People in the botensilimab groups will receive one of two doses of botensilimab alone or in combination with balstilimab. The trial opened in November 2022 at the City of Hope National Medical Center, California. Additional centers are now gearing up in 15 more US states and Europe. Investigators anticipate 230 participants. The primary outcome measure is objective response rate. OS is a secondary measure, and QoL will not be assessed. More details at clinicaltrials.gov
Goldberg said: "There is great interest in strategies that can effectively deploy immune-oncology agents in patients with microsatellite-stable cancers in general and colorectal cancers in particular. Promising data were recently presented that support studying this approach in a larger cohort of patients to extend these preliminary data, as it could be a strategy that unlocks the application of these agents in these patients ― an approach that has not been productive as of yet."
Metastatic and/or unresectable colorectal cancer with KRAS or NRAS mutations. Individuals with this type of cancer can enroll in a randomized, open-label, phase 2 study to test the investigational agent onvansertib (from Cardiff Oncology). For up to 2 years, all participants will receive standard of care: IV infusions of bevacizumab (Avastin) and FOLFIRI (irinotecan [Camptosar] + fluorouracil [5-FU] + leucovorin) every 2 weeks. The participants in the experimental group will also take oral capsules of onvansertib for 10 days out of 28. Research sites in 20 states started recruiting for 150 participants in January 2023. The primary endpoint is overall response rate. OS is a secondary measure. Investigators will not measure QoL. More details at clinicaltrials.gov
Commenting on this trial, Goldberg said: "Given poor response rates in colorectal cancer patients whose tumors harbor RAS mutations, novel approaches such as the addition of a polo-kinase inhibitor such as onvansertib, for which preclinical models support testing with an irinotecan-based regimen, [are] worth testing."
Previously treated unresectable metastatic colorectal cancer. Adult patients with this type of cancer are eligible to participate in a randomized, open-label, phase 2 trial designed to pinpoint the best dose of experimental therapy NUC-3373 (from NuCana). Individuals in the comparator group will receive standard of care: IV bevacizumab plus FOLFIRI every 2 weeks. People in one experimental arm will undergo a similar regimen, with NUC-3373 substituted for 5-FU. In the other experimental group, participants will receive NUC-3373 weekly instead of every 2 weeks. The Gabrail Cancer and Research Center, in Canton, Ohio, opened its doors in January 2023. Sites in Kansas and Europe are also planned. The investigators are looking to enroll a total of 171 participants. The primary outcome is PFS. OS is a secondary outcome, and QoL will not be tracked. More details at clinicaltrials.gov
"NUC-3373 is a thymidylate synthase inhibitor with greater potency in preclinical testing than 5-FU, which remains a cornerstone of chemotherapy in the treatment of colorectal and other cancers," commented Goldberg. "Since 5-FU has modest single-agent activity, the identification of more effective drugs in this class to use in combination chemotherapy regimens is a desirable goal that begins with this dose-finding effort."
All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).Goldberg is not involved with any of these trials.
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Cite this: New Trials in Colorectal Cancer: Could Your Patient Benefit? - Medscape - Mar 10, 2023.