Study on Regorafenib and Pembrolizumab for MSI-H Colorectal Cancer

Sponsor: Ibrahim Halil Sahin

Sponsor score: 0
Inactive

ClinicalTrials ID:NCT06006923

Provider View

This clinical trial is testing a combination of two drugs, Regorafenib and Pembrolizumab, to see if they can effectively treat patients with a specific type of colorectal cancer known as MSI-H. The study will first assess the safety and initial effectiveness of the treatment, followed by a more detailed examination of its benefits.

Patient Parameters

Program Overview

The purpose of this study is to evaluate if combining Regorafenib, a drug that targets cancer cell growth, with Pembrolizumab, an immunotherapy drug, can improve treatment outcomes for patients with MSI-H colorectal cancer. This type of cancer has a high level of genetic instability, making it more challenging to treat. The study will begin with a phase to test the safety and initial effectiveness of the combination, followed by a randomized phase to further explore its benefits.

Description

Regorafenib is a medication that targets multiple pathways involved in cancer cell growth, including those that help form new blood vessels in tumors. It may also affect the immune environment around the tumor. Early studies suggest that Regorafenib could work well with immune checkpoint inhibitors like Pembrolizumab, which is already approved for treating MSI-H colorectal cancer. However, there is still a need to enhance the effectiveness of these treatments for patients with this type of cancer.

The study will explore the potential benefits of combining Regorafenib and Pembrolizumab, especially since MSI-H colorectal cancer often shows increased activity of a protein called VEGF. A recent study indicated that patients with MSI-H colorectal cancer responded better to Regorafenib than those with a different type of colorectal cancer. This combination may boost the immune response against tumors and improve the effectiveness of immunotherapy.

In the initial phase, patients will receive a lower dose of Regorafenib (60 mg) along with Pembrolizumab (200 mg) every three weeks to ensure tolerance. The dose of Regorafenib will be increased to 90 mg in the second cycle. An interim analysis will be conducted after the initial phase, which aims to enroll about 22 patients. If successful, the study will proceed to a randomized phase with a target enrollment of 66 patients per group, totaling 154 participants. Patients who have had three or fewer cycles of chemotherapy before being diagnosed with MSI-H colorectal cancer can join this trial.

Eligibility Criteria

Inclusion Criteria

  • Diagnosed with advanced colorectal cancer that is mismatch repair deficient or has high microsatellite instability (MSI-H).
  • Have measurable cancer that can be tracked using standard criteria.
  • Be in good overall health with an ECOG performance status of 0 or 1, meaning fully active or restricted in physically strenuous activity but ambulatory.
  • Be 18 years or older.
  • Be able to swallow pills.
  • Have adequate organ function based on specific blood tests, including:
    • Neutrophil count of at least 1500/mm3.
    • Platelet count of at least 100,000/mm3.
    • White blood cell count of at least 2.5 × 10^9/L.
    • Hemoglobin level of at least 9 g/dL.
    • Liver enzymes and bilirubin levels within specified limits.
    • Kidney function within specified limits.
  • Have received no more than three cycles of certain chemotherapy regimens before joining the study.
  • Agree to use effective contraception during the study and for at least eight weeks after the last dose.
  • Have received no more than one cycle of Pembrolizumab alone before joining the initial phase of the trial.

Exclusion Criteria

  • Have previously received anti-PD-1 or anti-CTLA-4 therapies.
  • Have had more than three cycles of chemotherapy or disease progression on first-line therapy.
  • Have an active autoimmune disease.
  • Be pregnant or breastfeeding.
  • Have uncontrolled HIV, hepatitis B, or hepatitis C infections.
  • Have untreated brain metastases.
  • Have uncontrolled high blood pressure or recent cardiovascular events.
  • Have an active or chronic infection requiring ongoing antibiotics.
  • Have had another type of cancer within the past year, except for certain non-threatening cancers.
  • Have severe liver impairment.
  • Have had major surgery or significant injury within the past 28 days.
  • Have non-healing wounds or fractures.
  • Have a history of bleeding disorders or recent severe bleeding events.

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