Tremelimumab (Anti-CTLA-4) Plus MEDI4736 (Anti-PD-L1) in Resectable Colorectal Cancer Liver Metastases

• Status: Recruiting
• Trial end date: 0000-00-00
• Target enrollment: 35
• Participant gender: Both

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: MedImmune LLC
• Treatments: Antibodies; Antibodies, Monoclonal; Bevacizumab; Fluorouracil; Leucovorin; Levoleucovorin; Liver Extracts; Oxaliplatin; Tremelimumab
• Last Updated: 2016-11-28

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.