Clinical Trials /

Nivolumab and Ipilimumab and Radiation Therapy in MSS and MSI High Colorectal and Pancreatic Cancer

NCT03104439

Description:

This research study is studying a combination of drugs with radiation therapy as a possible treatment for Microsatellite Stable Colorectal Cancer, Pancreatic Cancer, or MSI High Colorectal Cancer. The interventions involved in this study are: - Nivolumab - Ipilimumab - Radiation Therapy

Related Conditions:
  • Colorectal Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and Ipilimumab and Radiation Therapy in MSS and MSI High Colorectal and Pancreatic Cancer
  • Official Title: Nivolumab and Ipilimumab and Radiation Therapy in Microsatellite Stable (MSS) and Microsatellite Instability (MSI) High Colorectal and Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17-021
  • NCT ID: NCT03104439

Conditions

  • Microsatellite Stable Colorectal Cancer
  • Pancreatic Cancer
  • MSI High Colorectal Cancer

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab+Ipilimumab
IpilimumabYervoyNivolumab+Ipilimumab

Purpose

This research study is studying a combination of drugs with radiation therapy as a possible treatment for Microsatellite Stable Colorectal Cancer, Pancreatic Cancer, or MSI High Colorectal Cancer. The interventions involved in this study are: - Nivolumab - Ipilimumab - Radiation Therapy

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational intervention to learn whether the intervention works
      in treating a specific disease. "Investigational" means that the intervention is being
      studied.

      The FDA (the U.S. Food and Drug Administration) has not approved nivolumab for this specific
      disease but it has been approved for other uses.

      The FDA (the U.S. Food and Drug Administration) has not approved ipilimumab for this
      specific disease but it has been approved for other uses.

      Researchers hope to study the effects of the combination of Nivolumab and Ipilimumab. Many
      cancers use specific pathways (such as PD-1/PD-L1 and CTLA-4) to evade the body's immune
      system. Nivolumab and ipilimumab work by blocking the PD-1/PD-L1 and CTLA-4 pathways and
      thus releasing the brakes on the immune system so it can stop or slow cancer.

      Ipilimumab and Nivolumab are both antibodies. An antibody is a cell that attaches to other
      cells to fight off infection. The antibodies in ipilimumab work by not allowing cancer cell
      growth. The antibodies in nivolumab work by causing programmed cell death of the cancer
      cells. Radiation therapy is believed to increase the likelihood of response of immunotherapy
      (the prevention/treatment of a disease through an immune response).

      In this research study, the investigators are studying the combination of nivolumab,
      ipilimumab and radiation therapy on participants with microsatellite stable colorectal
      cancer, pancreatic cancer, or MSI high colorectal cancer. The combination of these study
      drugs have been tested and optimized for safety and is currently being tested in multiple
      disease types. The study drugs have not been tested and optimized in combination with
      radiation therapy. The investigators believe that through the combination of the study drugs
      and radiation therapy the body may produce an immune response to stop the cancer cells from
      growing.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab+IpilimumabExperimentalNivolumab will be administered intravenously 3 times per cycle Ipilimumab will be administered intravenously once per cycle Radiation Therapy will be administered per hospital standard
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically or cytologically confirmed adenocarcinoma of
             colorectal or pancreatic origin

          -  Age >18 years.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤1

          -  Life expectancy of greater than 3 months

          -  Participants must have normal organ and marrow function as defined in Table 1, all
             screening labs should be performed within 14 days of protocol registration.

        Table 1 Adequate Organ Function Laboratory Values

        System Laboratory Value

          -  Hematological

               -  Absolute neutrophil count (ANC) ≥1500 /mcL

               -  White blood count (WBC) ≥2000 /mcL

               -  Platelets ≥100,000 / mcL

               -  Hemoglobin ≥9 g/dL

          -  Renal

               -  Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be
                  used in place of creatinine or CrCl) ≤ Serum creatinine ≤ 1.5 x ULN or
                  creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula
                  below):

               -  Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine
                  in mg/dL

               -  Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in
                  mg/dL

          -  Hepatic

               -  Serum total bilirubin ≤ 1.5 X ULN (upper limit of normal) (subjects with Gilbert
                  Syndrome can have a total bilirubin <3 mg/dL

               -  aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)
                  and Alanine Aminotransferase ALT (SGPT) ≤ 3 X ULN OR ≤ 5 X ULN for subjects with
                  liver metastases

          -  Coagulation

               -  International Normalized Ratio (INR) or Prothrombin Time (PT)

               -  Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is
                  receiving anticoagulant therapy

               -  as long as PT or PTT is within therapeutic range of intended use of
                  anticoagulants

                  ≤1.5 X ULN unless subject is receiving anticoagulant therapy

               -  as long as PT or PTT is within therapeutic range of intended use of
                  anticoagulants

          -  Creatinine clearance should be calculated per institutional standard.

          -  Women of childbearing potential (WOCBP) must use appropriate method(s) of
             contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months
             (30 days plus the time required for nivolumab to undergo five half-lives) after the
             last dose of investigational drug.

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             (minimum sensitivity 25 IU/L or equivalent units of HCG)

          -  Women must not be breastfeeding

          -  Men who are sexually active with WOCBP must use any contraceptive method with a
             failure rate of less than 1% per year. Men receiving nivolumab and who are sexually
             active with WOCBP will be instructed to adhere to contraception for a period of 7
             months after the last dose of investigational product. Women who are not of
             childbearing potential, ie, who are postmenopausal or surgically sterile as well as
             azoospermic men do not require contraception

          -  Ability to understand and the willingness to sign a written informed consent
             document.

          -  Stable dose of dexamethasone 2 mg or less for 7 days prior to initiation of treatment

          -  One previously unirradiated lesion amenable to radiotherapy 8 Gy x 3 and can meet
             dose constraints, and another unirradiated measurable lesion > 1 cm in size outside
             the radiation field that can be used as measurable disease

          -  Colorectal patients must have documentation of microsatellite status.
             Immunohistochemistry (IHC) is acceptable.

          -  Colorectal patients must have received prior Fluorouracil (5FU), Irinotecan and
             Oxaliplatin (any combination) or have a contraindication to receiving these agents.

          -  Pancreas patients must have progressed on at least 1 prior line of chemotherapy

        Exclusion Criteria:

          -  Participants who have had chemotherapy, targeted small molecule therapy or study
             therapy within 14 days of protocol treatment, or those who have not recovered (i.e.,
             ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2
             weeks earlier. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion
             and may qualify for the study. If subject received major surgery, they must have
             recovered adequately from the toxicity and/or complications from the intervention
             prior to starting therapy.

          -  Participants who are receiving any other investigational agents.

          -  Patients are excluded if they have an active, known or suspected autoimmune disease
             other than those listed below. Subjects are permitted to enroll if they have
             vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
             condition only requiring hormone replacement, psoriasis not requiring systemic
             treatment, or conditions not expected to recur in the absence of an external trigger

          -  Patients are excluded if they have a condition requiring systemic treatment with
             either corticosteroids (> 10 mg daily prednisone equivalents) or other
             immunosuppressive medications within 14 days of study drug administration. Inhaled or
             topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents
             are permitted in the absence of active autoimmune disease. Subjects are permitted to
             use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids
             (with minimal systemic absorption). Physiologic replacement doses of systemic
             corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief
             course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment
             of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by
             contact allergen) is permitted.

          -  Colorectal patients are excluded if they have had prior systemic treatment with an
             anti-CTLA4, anti-PD1 (Programmed cell death protein 1) or PDL1 (Programmed
             death-ligand 1) antibody. Pancreatic patients are excluded if they have previously
             received anti-CTLA-4 therapy. Prior PD-1 or PDL1 therapy will be permitted for
             pancreas patients

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  Patients are excluded if they are positive test for hepatitis B virus surface antigen
             (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or
             chronic infection

          -  Patients are excluded if they have known history of testing positive for human
             immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
             These participants are at increased risk of lethal infections when treated with
             marrow-suppressive therapy. Appropriate studies will be undertaken in participants
             receiving combination antiretroviral therapy when indicated.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  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 5 months for woman and 7 months for men, after the last dose of trial
             treatment.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of
             the skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  Has known history of, or any evidence of active, non-infectious pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.

          -  History of allergy to study drug components

          -  History of severe hypersensitivity reaction to any monoclonal antibody

          -  Uncontrolled brain metastases. Patients treated with radiation > 4 weeks prior with
             follow up imaging showing control are eligible
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease Control Rate
Time Frame:2 years
Safety Issue:
Description:The percentage of participants with disease control following treatment with nivolumab/ipilimumab/radiation. Disease control is defined as the percentage of participants who have achieved complete response (CR), partial response (PR), or stable disease (SD) as defined by Response Evaluation Criteria In Solid Tumors (RECIST). Tumors may be evaluated for response with X-ray, computerized tomography (CT) scan, Magnetic resonance imaging (MRI), FDG (fluorodeoxyglucose) positron emission tomography (PET) scan, PET-CT, or cytology/histology.

Secondary Outcome Measures

Measure:Median Progression free Survival
Time Frame:2 years
Safety Issue:
Description:Progression-Free Survival (PFS) is defined as the time from the first treatment date to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.
Measure:Median Overall Survival
Time Frame:2 years
Safety Issue:
Description:Overall Survival (OS) is defined as the time from the first treatment date to death due to any cause, or censored at date last known alive.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Pancreatic Cancer
  • Microsatellite Stable Colorectal Cancer

Last Updated

April 3, 2017