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Trial record 6 of 351 for:    colorectal | Recruiting | United States

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
MedImmune LLC
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT02754856
First received: April 26, 2016
Last updated: November 28, 2016
Last verified: November 2016
  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.

Condition Intervention Phase
Colorectal Cancer
Liver Metastases
Drug: Tremelimumab
Drug: Fluorouracil
Drug: Leucovorin
Drug: Oxaliplatin
Drug: Bevacizumab
Drug: MEDI4736
Procedure: Liver Resection
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Feasibility of Tremelimumab plus MEDI4736 with FOLFOX and Bevacizumab in Candidates for Resection of Colorectal Cancer Liver Metastases [ Time Frame: 15 weeks ] [ Designated as safety issue: Yes ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    Relapse-free survival (RFS) assessed from the date of study entry until relapse or death from any cause.


Estimated Enrollment: 35
Study Start Date: July 2016
Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tremelimumab + MEDI4736 + FOLFOX + Bevacizumab

Participants 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.

Drug: Tremelimumab
Tremelimumab 75 mg by vein as a flat dose during Week 11.
Drug: Fluorouracil
5-FU continuous infusion 2400 mg/m2 over 46 hours, 5-FU bolus 400 mg/m2 over about 2 days during Weeks 1, 3, 5, and 7.during Weeks 1, 3, 5, and 7.
Other Names:
  • 5-Fluorouracil
  • 5-FU
  • Adrucil
  • Efudex
Drug: Leucovorin
Leucovorin 400 mg/m2 by vein over about 2 days during Weeks 1, 3, 5, and 7.
Other Names:
  • Citrovorum
  • Wellcovorin
Drug: Oxaliplatin
Oxaliplatin 85 mg/m2 by vein over about 2 days during Weeks 1, 3, 5, and 7.
Other Name: Eloxatin
Drug: Bevacizumab
Bevacizumab 5 mg/kg by vein over about 2 days during Weeks 1, 3, 5, and 7.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
Drug: MEDI4736
MEDI4736 1500 mg by vein as a flat dose during Week 11. After Week 11, participant receives MEDI4736 alone by vein during Weeks 21, 25, 29, and 33.
Other Name: Durvalumab
Procedure: Liver Resection
Participant undergoes scheduled liver resection between Weeks 15 and 17.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02754856

Contacts
Contact: Michael Overman, MD 713-792-2828

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
MedImmune LLC
Investigators
Principal Investigator: Michael Overman, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02754856     History of Changes
Other Study ID Numbers: 2015-0828  NCI-2016-00772 
Study First Received: April 26, 2016
Last Updated: November 28, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases
Liver Extracts
Bevacizumab
Oxaliplatin
Tremelimumab
Fluorouracil
Leucovorin
Antibodies
Antibodies, Monoclonal
Levoleucovorin
Hematinics
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances

ClinicalTrials.gov processed this record on December 08, 2016