Lead Investigator: Michael Szarek, CPC Clinical Research
Title of Proposal Research: Comparison of RGX-202-01 with ramucirumab or aflibercept in the treatment of patients with recurrent colorectal cancer harboring a RAS mutation
Vivli Data Request: 8758
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Colorectal Cancer (CRC) is the fourth most frequent cancer diagnosis and the second leading cause of cancer death in the United States (US). In 2020, there were an estimated 147,950 new cases of colon cancer and 53,000 deaths due to metastatic CRC (mCRC). While the overall incidence of CRC had been declining during the past few decades (60.5 per 100,000 people in 1976 versus 38.7 per 100,000 people in 2016), the incidence among those who are younger than 50 has been rising 2% annually.
Colorectal cancer can spread (metastasis) around the body in the blood vessels or through the lymphatic system (a network of vessels and lymph nodes that keeps body fluid levels in balance and defends the body against infections). The most common metastatic sites being liver, lungs, and peritoneum (a membrane that surrounds the abdominal organs). For most patients with mCRC, treatment will be palliative, or symptom relieving rather than curative, and consequently treatment goals are to prolong overall survival (OS) and maintain quality of life (QOL) for as long as possible. However, some patients with stage IV disease (particularly those with liver- or lung-limited metastases) can be surgically cured of their disease. Furthermore, a subset of patients with mCRC who initially have unresectable (cannot be removed through surgery) liver or lung metastases may be rendered candidates for curative resection if the disease response to chemotherapy is sufficient.
Therapeutic options for patients with mCRC had expanded from an era 30 years ago, where 5-fluorouracil (5-FU) was the single approved therapy and median OS was 11-12 months. It works by stopping cancer cells making and repairing DNA so they cannot grow and multiply. Currently, median OS is approaching 3 years with 20% surviving 5 years. This improvement in survival and in disease control has been achieved with a better understanding of the biology of the disease, leading to the approval of additional therapies. In parallel, advances in supportive care, such as effective antiemetic (drugs that stop nausea and vomiting) as well as other supportive therapies, improved the tolerance to therapy and the quality of life of patients with mCRC. Yet, despite the significant progress, for most patients, mCRC is still an incurable disease and further therapeutic advances are needed.
The most common first-line regimen (the best initial treatment) for advanced mCRC in the US consists of the chemotherapies oxaliplatin and 5-FU (FOLFOX) which interfere with cancer cell growth in combination with bevacizumab which works by limiting the blood supply to the tumor. Furthermore, the addition of irinotecan (which prevents tumor growth by stopping cancer cells dividing) to FOLFOX (FOLFOXIRI) when combined with bevacizumab appears to provide OS benefit as a first-line regimen and is typically used in patients with high performance status (PS) (a measure of a person’s general health) and in patients with borderline resectable disease.
Approximately 70% of patients who have progressive disease (PD) on first-line therapy will receive second-line therapy (the next best treatment). The most common second-line therapy in the US is irinotecan and 5-FU (FOLFIRI) in combination with bevacizumab, which includes patients that received bevacizumab as first-line therapy. The median progression-free survival (PFS) and OS among patients who receive second-line therapy with bevacizumab or other therapies that work in the same way, e.g., ramucirumab or aflibercept, in combination with chemotherapy in clinical studies are generally 5-6 months and 11-12 months, respectively, although in a recent study median OS was longer at 15-18 months.
RGX-202-01 is an oral (by mouth) drug being developed for the treatment of patients with gastrointestinal (GI) malignancies. A clinical study has shown that patients with recurrent colorectal cancer harboring a RAS (gene) mutation seem to benefit from treatment with RGX-202-01 relative to historical data. However, since the study had no control group (patients who didn’t take the new drug for comparison) it is not clear if this apparent benefit is due to treatment with the agent, the characteristics of the patients, or a combination of both. Therefore this proposed research project aims to further explore this potential benefit by matching patients treated with RGX-201-01 with similar patients in studies of ramucirumab and aflibercept.
A Randomized, Double-blind, Multicenter Phase 3 Study of Irinotecan, Folinic Acid, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab or Placebo in Patients With Metastatic Colorectal Carcinoma Progressive During or Following First-Line Combination Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine
Data Contributor: Lilly
Study ID: NCT01183780
Sponsor ID: 13856
A Multinational, Randomized, Double-blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks Versus Placebo in Patients With Metastatic Colorectal Cancer (MCRC) Treated With Irinotecan / 5-FU Combination (FOLFIRI) After Failure of an Oxaliplatin Based Regimen
Data Contributor: Sanofi
Study ID: NCT00561470
Sponsor ID: EFC10262
A Study of RGX-202-01 as Combination Therapy in 2nd Line RAS Mutant Advanced Colorectal Cancer
Data Contributor: I WILL BRING MY OWN
Study ID: NCT03597581
Sponsor ID: NCT03597581