Clinical Trials /

Tremelimumab and Durvalumab in Treating Patients With Colorectal Cancer With Liver Metastases That Can Be Removed by Surgery

NCT02754856

Description:

This phase I trial studies the side effects and how well tremelimumab and durvalumab work in treating patients with colorectal cancer that has spread to the liver and can be removed by surgery. Immunotherapy with monoclonal antibodies, such as tremelimumab and durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Tremelimumab (Anti-CTLA-4) Plus MEDI4736 (Anti-PD-L1) in Resectable Colorectal Cancer Liver Metastases
  • Official Title: Pilot Study Assessing the Safety and Tolerability of the Neoadjuvant Use of Tremelimumab (Anti-CTLA-4) Plus MEDI4736 (Anti-PD-L1) in the Treatment of Resectable Colorectal Cancer Liver Metastases

Clinical Trial IDs

  • ORG STUDY ID: 2015-0828
  • SECONDARY ID: NCI-2016-00772
  • NCT ID: NCT02754856

Conditions

  • Colorectal Cancer
  • Liver Metastases

Interventions

DrugSynonymsArms
TremelimumabTremelimumab + MEDI4736 + FOLFOX + Bevacizumab
Fluorouracil5-Fluorouracil, 5-FU, Adrucil, EfudexTremelimumab + MEDI4736 + FOLFOX + Bevacizumab
LeucovorinCitrovorum, WellcovorinTremelimumab + MEDI4736 + FOLFOX + Bevacizumab
OxaliplatinEloxatinTremelimumab + MEDI4736 + FOLFOX + Bevacizumab
BevacizumabAvastin, Anti-VEGF monoclonal antibodyTremelimumab + MEDI4736 + FOLFOX + Bevacizumab
MEDI4736DurvalumabTremelimumab + MEDI4736 + FOLFOX + Bevacizumab

Purpose

The goal of this clinical research study is to learn if tremelimumab in combination with MEDI4736, FOLFOX (fluorouracil, leucovorin, and oxaliplatin), and bevacizumab can help to control colorectal cancer that has spread to the liver. The safety of these drugs will also be studied.

Detailed Description

      Study Drug Administration:

      If participant is found to be eligible to take part in this study, they will receive FOLFOX
      and bevacizumab by vein over about 2 days during Weeks 1, 3, 5, and 7.

      Participant will also receive tremelimumab by vein over about 1 hour and MEDI4736 by vein
      over about 4 hours during Week 11. After Week 11, participant will receive MEDI4736 alone by
      vein over about 1 hour during Weeks 21, 25, 29, and 33.

      Between Weeks 15 and 17, participant will have their already scheduled liver surgery. This
      means participant will receive FOLFOX, bevacizumab, and tremelimumab before their surgery
      and MEDI4736 after their surgery.

      Study Visits:

      During Week 1:

        -  Participant will have a physical exam.

        -  Blood (about 6 tablespoons) will be drawn for routine tests and for testing related to
           participant's immune system.

        -  If participant can become pregnant, part of the above routine blood sample will be used
           for a pregnancy test. Urine may also be collected for this test.

      During Weeks 3, 5, and 7:

        -  Blood (about 1 tablespoon) will be drawn for routine tests.

        -  During Week 5, participant will have a physical exam.

      Between Weeks 9 and 11:

        -  Blood (about 4 tablespoons) will be drawn for tests related to the immune system.

        -  Participant will have a CT scan.

        -  Participant will have a liver tumor biopsy to check the status of the disease and for
           biomarker testing. To perform a tumor tissue biopsy, the affected area is numbed with
           anesthetic and a small amount of tissue is removed with a small needle. Participant
           will also receive anesthesia before the procedure. This will be discussed with
           participant in more detail before the biopsy.

      During Week 11:

        -  Participant will have a physical exam.

        -  Blood (about 4 teaspoons) will be drawn for routine tests.

        -  If participant can become pregnant, part of the above routine blood sample will be used
           for a pregnancy test. Urine may also be collected for this test.

      During Week 15:

        -  Participant will have a physical exam.

        -  Blood (about 5 tablespoons) will be drawn for routine tests and tests related to
           participant's immune system.

        -  Participant will have a CT scan.

      Between Weeks 15 and 17, participant will have liver surgery as part of their standard care.
      Participant will sign a separate consent form for this procedure.

      During Weeks 19:

        -  Participant will also have a physical exam.

        -  Blood (about 7 tablespoons) will be drawn for routine tests, to check the status of the
           disease, and for tests related to participant's immune system.

      During Week 21:

        -  Participant will have a physical exam.

        -  Blood (about 4 teaspoons) will be drawn for routine tests.

        -  If participant can become pregnant, part of the above routine blood sample will be used
           for a pregnancy test. Urine may also be collected for this test.

      During Week 25:

        -  Participant will have a physical exam.

        -  Blood (about 4 teaspoons) will be drawn for routine tests.

      During Weeks 29, 44, and 68:

        -  Participant will have a physical exam.

        -  Blood (about 8 teaspoons) will be drawn for routine tests and to check the status of
           the disease.

        -  Participant will have a CT scan or MRI.

      During Week 33:

        -  Participant will have a physical exam.

        -  Blood (about 6 tablespoons) will be drawn for routine tests and tests related to
           participant's immune system.

      During Week 56:

        -  Participant will have a physical exam.

        -  Blood (about 7 tablespoons) will be drawn for routine tests, to check the status of the
           disease, and for tests related to participant's immune system.

        -  Participant will have a CT scan.

      Length of Study:

      Participant may receive FOLFOX and bevacizumab during Weeks 1, 3, 5, and 7. Participant may
      receive tremelimumab and MEDI4736 for 1 week and MEDI4736 alone for up to an additional 4
      weeks. Participant will no longer be able to take the study drugs if the disease gets worse,
      if intolerable side effects occur, or if they are unable to follow study directions.

      Patient's participation on this study will be over after follow-up.

      Follow-Up:

      If participant stops treatment for any reason, they will be asked to come to the hospital so
      their study doctor may check their health and follow up any ongoing side effects or
      discomfort until they get better.

      If the disease has gotten better or remained the same, participant's doctor will continue to
      check on the status of the disease as part of their standard of care, which may include
      imaging scans and/or blood draws for routine tests.

      Follow-up will continue for 1½ years or until participant withdraws from the study.

      This is an investigational study. MEDI4736 and tremelimumab are not FDA approved or
      commercially available. They are currently being used for research purposes only. FOLFOX and
      bevacizumab are FDA approved and commercially available for the treatment of colorectal
      cancer.

      The study doctor can explain how the study drugs are designed to work.

      Up to 35 participants will take part in this study. All will be enrolled at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Tremelimumab + MEDI4736 + FOLFOX + BevacizumabExperimentalParticipants receive FOLFOX (Fluorouracil, Leucovorin, and Oxaliplatin), and Bevacizumab by vein over about 2 days during Weeks 1, 3, 5, and 7. Participants also receive Tremelimumab by vein over about 1 hour and MEDI4736 by vein over about 4 hours during Week 11. After Week 11, participants receives MEDI4736 alone by vein over about 1 hour during Weeks 21, 25, 29, and 33. Between Weeks 15 and 17, participant undergoes scheduled liver surgery.
  • Tremelimumab
  • Fluorouracil
  • Leucovorin
  • Oxaliplatin
  • Bevacizumab
  • MEDI4736

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must have histologically or cytologically confirmed colorectal cancer with
             metastases deemed resectable by a general or liver surgeon (resectability may involve
             the use of ablative techniques to some but not all liver metastases). Those patients
             with known disease outside of the liver are not eligible (except for patients with
             primary lesions in place that are planned for resection or nonspecific lung
             metastases <1cm).

          2. Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as
             =/>10 mm with spiral CT scan.

          3. All lines of prior therapy accepted. Subjects with prior hepatic or extra-hepatic
             resections of metastatic disease will be included.

          4. Age =/>18 years. Because no dosing or adverse event data are currently available on
             the use of tremelimumab in combination with MEDI4736 in patients <18 years of age,
             children are excluded from this study.

          5. Life expectancy of greater than 6 months.

          6. ECOG performance status =/<1 (Karnofsky =/>70%).

          7. Patients must have normal organ and marrow function as defined: a) leukocytes
             =/>3,000/mcL; b) absolute neutrophil count =/>1,500/mcL; c) platelets =/>100,000/mcL;
             d) total bilirubin < 1.5 X institutional normal limits (subjects with known Gilbert
             syndrome are eligible with total bilirubin < 3.0 mg/dL); e) AST(SGOT)/ALT(SGPT) =/< 3
             X institutional upper limit of normal; f) creatinine within normal institutional
             limits OR g) creatinine clearance =/>60 mL/min/1.73 m^2 for patients with creatinine
             levels above institutional normal.

          8. Known MSI, BRAF, and KRAS status.

          9. The effects of tremelimumab and/or MEDI4736 on the developing human fetus at the
             recommended therapeutic dose are unknown. For this reason and because immune
             checkpoint inhibitors as well as other therapeutic agents used in this trial are
             known to be teratogenic, women of child-bearing potential and men must agree to use
             adequate contraception (hormonal or barrier method of birth control; abstinence)
             prior to study entry, for the duration of study participation, and 180 days after the
             last dose of tremelimumab. Should a woman become pregnant or suspect she is pregnant
             while participating in this study, she should inform her treating physician
             immediately.

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

        Exclusion Criteria:

          1. Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
             the study or those who have not recovered from adverse events due to agents
             administered more than 4 weeks earlier. An exception to this criterion is if patients
             are enrolled after the completion of neoadjuvant chemotherapy. If this is the case
             then 2 weeks must elapse prior to the beginning of immune checkpoint therapy.

          2. Patients may not be receiving any other investigational agents.

          3. Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the
             exception of diverticulosis], celiac disease, systemic lupus erythematosus,
             Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves'
             disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are
             exceptions to this criterion: a) Patients with vitiligo or alopecia; b) Patients with
             hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement; c)
             Any chronic skin condition that does not require systemic therapy; d) Patients
             without active disease in the last 5 years may be included but only after
             consultation with the study physician.

          4. Subjects with a condition requiring systemic treatment with either corticosteroids
             (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14
             days of study drug administration. Inhaled or topical steroids and adrenal
             replacement doses > 10mg daily prednisone equivalents are permitted in the absence of
             active autoimmune disease.

          5. Prior exposure to T cell checkpoint inhibitor therapies.

          6. 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.

          7. Positive test for hepatitis B virus surface antigen or hepatitis C (IgG or RNA test)
             indicating acute or chronic infection.

          8. Positive test for HIV.

          9. Women who are pregnant, which includes women with a positive pregnancy test at
             enrollment or prior to the administration of study medication, or breastfeeding are
             not allowed on study.

         10. Receipt of a live vaccine within 30 days of study entry.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Feasibility of Tremelimumab plus MEDI4736 with FOLFOX and Bevacizumab in Candidates for Resection of Colorectal Cancer Liver Metastases
Time Frame:15 weeks
Safety Issue:
Description:Feasibility assessed by whether or not the patient successfully goes to surgery following the planned treatments, scans, and biopsy. Combination regimen considered feasible if at least 80% of patients successfully undergo surgery. It will be infeasible if fewer than 60% of patients can undergo surgery.

Secondary Outcome Measures

Measure:Relapse-free survival (RFS) of Tremelimumab plus MEDI4736 with FOLFOX and Bevacizumab in Candidates for Resection of Colorectal Cancer Liver Metastases
Time Frame:56 weeks
Safety Issue:
Description:Relapse-free survival (RFS) assessed from the date of study entry until relapse or death from any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Colorectal Cancer
  • Liver Metastases
  • Resectable liver metastases
  • Tremelimumab
  • Fluorouracil
  • 5-Fluorouracil
  • 5-FU
  • Adrucil
  • Efudex
  • Leucovorin
  • Citrovorum
  • Wellcovorin
  • Oxaliplatin
  • Eloxatin
  • Bevacizumab
  • Avastin
  • Anti-VEGF monoclonal antibody
  • MEDI4736
  • Durvalumab

Last Updated

March 29, 2017