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Trial record 6 of 385 for:    colorectal | Recruiting Studies | United States

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

This study is currently recruiting participants.
Verified September 2017 by M.D. Anderson Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02754856
First Posted: April 28, 2016
Last Update Posted: September 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
MedImmune LLC
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
  Purpose

The goal of this clinical research study is to learn if tremelimumab in combination with MEDI4736 can help to control colorectal cancer that has spread to the liver. The safety of these drugs will also be studied.

This is an investigational study. MEDI4736 and tremelimumab are not FDA approved or commercially available. They are currently being used for research purposes only.

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.


Condition Intervention Phase
Colorectal Cancer Liver Metastases Drug: Tremelimumab Drug: MEDI4736 Procedure: Liver Resection Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study Assessing the Safety and Tolerability of the Neoadjuvant Use of Tremelimumab (Anti-CTLA-4) Plus Durvalumab (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 ]
    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 ]
    Relapse-free survival (RFS) assessed from the date of study entry until relapse or death from any cause.


Estimated Enrollment: 35
Actual Study Start Date: July 28, 2016
Estimated Study Completion Date: July 2021
Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tremelimumab + MEDI4736

Participants 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: 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have histologically or cytologically confirmed colorectal cancer with liver 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 durvalumab 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 or ordered molecular testing for MSI, BRAF, and KRAS status.
  9. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  10. Continuation from criteria above: Women >/= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  11. Ability to understand and the willingness to sign a written informed consent document.
  12. Weight >30kg (required for flat dose-based administration of study agents)

Exclusion Criteria:

  1. Prior chemotherapy < 2 weeks prior to study drug treatment and treatment related adverse events that have not recovered to baseline or grade 1 (alopecia excluded). Prior radiation therapy <4weeks prior to study drug treatment.
  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], 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; d) Patients with celiac disease controlled by diet alone.
  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, including durvalumab and tremelimumab.
  6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  7. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  8. History of active primary immunodeficiency
  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.
  11. Any unresolved toxicity NCI CTCAE Grade >/=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria: a) Patients with Grade >/=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician; b) Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
  12. Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  13. Major surgical procedure within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  14. History of allogenic organ transplantation.
  15. Known active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  16. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or180 days after the last dose of durvalumab + tremelimumab combination therapy.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 ( Registry Identifier: NCI CTRP )
First Submitted: April 26, 2016
First Posted: April 28, 2016
Last Update Posted: September 13, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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
Fluorouracil
Tremelimumab
Antibodies, Monoclonal
Hematinics
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs