A Phase 2 Study of Pembrolizumab (MK-3475) in Combination With Azacitidine in Subjects With Chemo-refractory Metastatic Colorectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- Anuradha Krishnamurthy
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is an open label, single-arm, Phase 2 trial to evaluate the anti-tumor activity, safety, and tolerability of Pembrolizumab in combination with azacitidine in subjects with chemo-refractory mCRC without any further standard treatment options
Dosage and regimen for all study periods
- Pembrolizumab will be given at 200 mg every 21 days.
- Azacitidine will be given at 100 mg daily subcutaneous injection on days 1-5 every 21 days.
The first assessment of tumor response will be performed after cycle 3 (9 weeks), and thereafter approximately every 9 weeks, every 3 cycles of therapy. The modified RECIST 1.1 will be used to establish disease response or progression.
All patients will be evaluated and graded for adverse events according to the NCI Common Terminology for Adverse Events, version 4.0 (NCI-CTCAE).
Investigators
Anuradha Krishnamurthy
Assistant Professor
University of Pittsburgh
Eligibility Criteria
Inclusion Criteria
- •Be willing and able to provide written informed consent/assent for the trial.
- •Be 18 years of age or older on day of signing informed consent.
- •The diagnosis of mCRC will be based on histologic or cytologic confirmation.
- •Have mCRC that has been previously treated with currently approved standard therapies.
- •Have measurable disease based on RECIST 1.
- •At least 1 of the tumor sites must be amenable to core needle biopsy and this may not be the site of disease used to measure antitumor response. Patient must agree to this mandatory biopsy.
- •Have a performance status of 0 or 1 on the ECOG Performance Scale.
- •Demonstrate adequate organ function, all screening labs should be performed within 14 days of treatment initiation.
- •Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
Exclusion Criteria
- •Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- •Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- •Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy..
- •Has extensive metastatic tumor burden in the liver with serum albumin \<3.0 g/dL.
- •Has known renal tubular acidosis with serum bicarbonate \<20 mEq/L.
- •Has a known hypersensitivity to azacitidine or mannitol.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
Arms & Interventions
Pembrolizumab and Azacitidine Arm
9 cycles * Pembrolizumab will be given at 200 mg every 21 days. * Azacitidine will be given at 100 mg daily subcutaneous injection on days 1-5 every 21 days.
Intervention: Pembrolizumab
Pembrolizumab and Azacitidine Arm
9 cycles * Pembrolizumab will be given at 200 mg every 21 days. * Azacitidine will be given at 100 mg daily subcutaneous injection on days 1-5 every 21 days.
Intervention: Azacitidine
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: Up to 14 months
The objective response rate is estimated by the proportion (percentage) of participants with the best response of complete response (CR), or partial response (PR) by RECIST 1.1 criteria, with corresponding exact 95% confidence limits being reported. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Secondary Outcomes
- Progression-free Survival (PFS)(Up to 2 years)
- Overall Survival (OS)(Up to 2 years)