Study of Pembrolizumab in Combination With Chemotherapy for Patients With Advanced Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Pembrolizumab; mFOLFOX6
Intervention description: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks; mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days)
Oxaliplatin 85 mg/m^2 IV with
Leucovorin 400 mg/m^2 IV followed by
5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pembrolizumab; MK-3475

Summary:

      This is a multi-institutional, single arm, open-label, phase II study, including a safety
      run-in cohort. No randomization or blinding involved.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent for the trial and HIPAA
             authorization for release of personal health information. NOTE: HIPAA authorization
             may be included in the informed consent or obtained separately.

          -  Be ≥ 18 years of age on day of signing informed consent.

          -  Have a performance status of 0 or 1 on the ECOG Performance Scale within 14 days prior
             to registration.

          -  Have histological or cytological evidence of colorectal adenocarcinoma with
             confirmation of metastatic disease either by pathologic or radiologic findings.

          -  Have identified tissue from an archival tissue sample (preferably from a metastasis,
             but sample from primary tumor allowable) or newly obtained core or excisional biopsy
             of a tumor lesion.

          -  Have had no prior systemic therapy for advanced or metastatic disease. Prior adjuvant
             therapy should have been completed at least 9 months from documentation of metastatic
             disease. Prior palliative radiotherapy allowed if toxicities resolved to grade 1 or
             baseline.

          -  Have measurable disease according to RECIST v1.1 obtained by imaging within 28 days
             prior to registration.

          -  Female subjects of childbearing potential should have a negative urine or serum
             pregnancy test within 14 days prior to study registration. If the urine test is
             positive or cannot be confirmed as negative, a serum pregnancy test will be required.
             Subjects of childbearing potential (regardless of sexual orientation, having undergone
             a tubal ligation, or remaining celibate by choice) are those who meet the following
             criteria: has not undergone a hysterectomy or bilateral oophorectomy; OR has not been
             naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at
             any time in the preceding 12 consecutive months).

          -  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

        Exclusion Criteria:

          -  Has clearly resectable colon cancer liver metastases (CCLM), for example
             oligometastatic disease involving only one lobe of the liver. Subjects with suspected
             resectable CCLM should undergo evaluation by a liver surgeon prior to enrollment to
             document the incurable nature of their disease.

          -  Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device within 4 weeks of registration. Subjects are
             not permitted to participate in another investigational drug study while being treated
             on this protocol.

          -  Is unable to receive a port or peripherally inserted central catheter (PICC).

          -  Has a diagnosis of immunodeficiency or is receiving chronic steroid therapy of
             prednisone ≥ 10 mg daily or any equivalent dose of corticosteroids.

          -  Has previously undergone organ or bone marrow transplantation and is on
             immunosuppressive therapy

          -  Has had major surgery or significant traumatic injury within 4 weeks of study
             registration. Subjects must have recovered adequately from the toxicity and/or
             complications from the intervention prior to starting therapy. A diagnostic or
             research biopsy does not exclude subjects from enrollment. Placement of a vascular
             access device such as a Port-A-Cath is not considered major surgery

          -  Has baseline peripheral neuropathy/paresthesia grade ≥ 1.

          -  Has a known additional malignancy within the past 3 years. Exceptions include treated
             localized basal cell or squamous cell carcinoma of the skin, in situ cervical or
             vulvar carcinoma that has undergone potentially curative therapy, superficial bladder
             tumors (Ta, Tis & T1), ductal carcinoma in situ (DCIS) of the breast and low grade
             prostate cancer (Gleason sore 6). Any cancer curatively treated > 3 years prior to
             registration with no clinical evidence of recurrence is permitted

          -  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 trial registration 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 registration.

          -  Has an active autoimmune disease requiring systemic treatment within the past 3 months
             or a documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids or immunosuppressive agents. Exceptions to the rule:
             subjects with vitiligo; subjects with resolved childhood asthma/atopy; subjects that
             require intermittent use of bronchodilators or local steroid injections; subjects with
             hypothyroidism stable on hormone replacement or patients with Sjögren's syndrome

          -  Has a history of pneumonitis that required steroids or current pneumonitis.

          -  Has known history of active tuberculosis.

          -  Has an active infection requiring systemic therapy (≥ grade 2) for more than 3 days
             within 1 week of enrollment.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of pembrolizumab (MK-3475).

          -  Has known hypersensitivity to fluorouracil (5FU), oxaliplatin, or other platinum
             agents.

          -  Known hypersensitivity to pembrolizumab or any of its excipients.

          -  Has known dihydropyrimidine dehydrogenase deficiency (DPD) deficiency (testing not
             required)

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
             anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways).

          -  Has known active Hepatitis B unless subject has been on antiviral agents for at least
             2 months (baseline testing not required)

          -  Has a known history of Human Immunodeficiency Virus (HIV) or Hepatitis C (baseline
             testing is not required).

          -  Has received a live vaccine within 30 days prior to trial registration.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the site investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Has any other psychological, familial, sociological or geographical condition
             potentially hampering compliance with the study protocol and follow-up schedule. Those
             conditions should be discussed with the subject before registration in the trial.