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

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ClinicalTrials.gov Identifier: NCT02754856
Recruitment Status : Recruiting
First Posted : April 28, 2016
Last Update Posted : May 24, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Carcinoma in the Liver Resectable Mass Stage IV Colorectal Cancer AJCC v7 Stage IVA Colorectal Cancer AJCC v7 Stage IVB Colorectal Cancer AJCC v7 Biological: Durvalumab Other: Laboratory Biomarker Analysis Procedure: Therapeutic Conventional Surgery Biological: Tremelimumab Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. Assess the safety and feasibility of adding tremelimumab 75 mg intravenously (IV) plus durvalumab (MEDI4736) 1500 mg administered once pre-operatively and 4 cycles of durvalumab 1500 mg IV every 4 weeks for 4 cycles post-operatively in patients who are candidates for resection for colorectal cancer liver metastases.

SECONDARY OBJECTIVES:

I. Explore the changes in various immune parameters, including programmed cell death-1 ligand 1 (PD-L1) and programmed cell death1 (PD-1) expression in the tumor, over treatment and correlate with response and survival with goal of biomarker discovery.

II. Estimate the relapse-free survival (RFS) in all enrolled subjects.

OUTLINE:

Patients receive tremelimumab IV over 1 hour and durvalumab IV over 4 hours during week 11. Between weeks 15 and 17, patients undergo liver surgery. Patients then receive durvalumab IV over 1 hour during weeks 21, 25, 29, and 33.

After completion of study treatment, patients are followed up twice a year for 5 years.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
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
Actual Study Start Date : July 28, 2016
Estimated Primary Completion Date : July 30, 2021
Estimated Study Completion Date : July 30, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Treatment (tremelimumab, durvalumab)
Patients receive tremelimumab IV over 1 hour and durvalumab IV over 4 hours during week 11. Between weeks 15 and 17, patients undergo liver surgery. Patients then receive durvalumab IV over 1 hour during weeks 21, 25, 29, and 33.
Biological: Durvalumab
Given IV
Other Names:
  • Imfinzi
  • Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
  • MEDI-4736
  • MEDI4736

Other: Laboratory Biomarker Analysis
Correlative studies

Procedure: Therapeutic Conventional Surgery
Undergo liver surgery

Biological: Tremelimumab
Given IV
Other Names:
  • Anti-CTLA4 Human Monoclonal Antibody CP-675,206
  • CP-675
  • CP-675,206
  • CP-675206
  • Ticilimumab




Primary Outcome Measures :
  1. Feasibility: number of patients who successfully go to surgery after treatments, scans, and biopsy [ Time Frame: Up to 17 weeks ]
    Will be defined as the number of patients who successfully go to surgery after treatments, scans, and biopsy. A Bayesian sequential monitoring design will be used to monitor the trial for surgery rates.

  2. Incidence of adverse events [ Time Frame: Up to 1.5 years ]
    Will be assessed by Common Terminology Criteria of Adverse Events version 4.03. A Bayesian sequential monitoring design will be used to monitor the trial for toxicity rates.



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

Inclusion Criteria:

  • 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 < 1 cm)
  • 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 computed tomography (CT) scan
  • All lines of prior therapy accepted; subjects with prior hepatic or extra-hepatic resections of metastatic disease will be included
  • Life expectancy of greater than 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin < 1.5 X institutional normal limits (subjects with known Gilbert syndrome are eligible with total bilirubin < 3.0 mg/dL)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =< 3 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Known or ordered molecular testing for MSI, BRAF, and KRAS status
  • 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)
    • 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)
  • Ability to understand and the willingness to sign a written informed consent document
  • Weight > 30 kg (required for flat dose-based administration of study agents)

Exclusion Criteria:

  • 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 < 4 weeks prior to study drug treatment
  • Patients may not be receiving any other investigational agents
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., 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 (e.g., 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
  • Subjects with 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
  • Prior exposure to T cell checkpoint inhibitor therapies, including durvalumab and tremelimumab
  • 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
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
  • History of active primary immunodeficiency
  • 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
  • Receipt of a live vaccine within 30 days of study entry
  • Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (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
  • 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
  • Major surgical procedure within 28 days prior to the first dose of IP; Note: local surgery of isolated lesions for palliative intent is acceptable
  • History of allogenic organ transplantation
  • Known active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [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 (hepatitis C virus [HCV]) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
  • 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 or 180 days after the last dose of durvalumab + tremelimumab combination therapy

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
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Contact: Michael Overman, MD 713-792-2828 moverman@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Michael J. Overman    713-792-2828      
Principal Investigator: Michael J. Overman         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Michael J Overman M.D. Anderson Cancer Center

Additional Information:
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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: CTRP (Clinical Trial Reporting Program) )
2015-0828 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: April 28, 2016    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Durvalumab
Ipilimumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs