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Study of Binimetinib + Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer With RAS Mutation

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ClinicalTrials.gov Identifier: NCT03271047
Recruitment Status : Active, not recruiting
First Posted : September 1, 2017
Last Update Posted : July 29, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Array BioPharma

Brief Summary:
This is a multicenter, open-label, Phase 1B/2 study to evaluate the safety and assess the preliminary anti-tumor activity of binimetinib administered in combination with nivolumab or nivolumab + ipilimumab in adult patients with advanced metastatic colorectal cancer (mCRC) with microsatellite stable (MSS) disease and presence of a RAS mutation that have received at least one prior line of therapy and no more than 2 prior lines of therapy. The study contains a Phase 1b period to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) and schedule of binimetinib followed by a randomized Phase 2 period to assess the efficacy of the combinations.

Condition or disease Intervention/treatment Phase
MSS RAS-mutant Colorectal Cancer Drug: binimetinib Drug: nivolumab Drug: ipilimumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: In phase 1 it is sequential and then in phase 2 it is parallel.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase 1b/2 Study of Binimetinib Administered in Combination With Nivolumab or Nivolumab Plus Ipilimumab in Patients With Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer With RAS Mutation
Actual Study Start Date : October 4, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1b / Arm 1A
binimetinib + nivolumab
Drug: binimetinib
Orally, twice daily.

Drug: nivolumab
Intravenously (IV) every 4 weeks (Q4W)

Experimental: Phase 1b / Arm 1B
binimetinib + nivolumab + ipilimumab
Drug: binimetinib
Orally, twice daily.

Drug: nivolumab
Intravenously (IV) every 4 weeks (Q4W)

Drug: ipilimumab
intravenously (IV) every 8 weeks (Q8W)

Experimental: Phase 2 / Arm 2A
binimetinib + nivolumab
Drug: binimetinib
Orally, twice daily.

Drug: nivolumab
Intravenously (IV) every 4 weeks (Q4W)

Experimental: Phase 2 / Arm 2B
binimetinib + nivolumab + ipilimumab
Drug: binimetinib
Orally, twice daily.

Drug: nivolumab
Intravenously (IV) every 4 weeks (Q4W)

Drug: ipilimumab
intravenously (IV) every 8 weeks (Q8W)




Primary Outcome Measures :
  1. (Phase 1b) Incidence of dose-limiting toxicities (DLTs) resulting from binimetinib in combination with nivolumab [ Time Frame: Duration of each treatment cycle, 28 days ]
  2. (Phase 1b) Incidence of dose-limiting toxicities (DLTs) resulting from binimetinib in combination with nivolumab plus ipilimumab [ Time Frame: Duration of each treatment cycle, 28 days ]
  3. (Phase 2) Objective Response Rate (ORR) [ Time Frame: Duration of each treatment cycle, 28 days ]

Secondary Outcome Measures :
  1. (Phase 1b) Objective Response Rate (ORR) [ Time Frame: Duration of each treatment cycle, 28 days ]
  2. (Phase 1b and Phase 2) Duration of Response (DOR) [ Time Frame: Duration of each treatment cycle, 28 days ]
  3. (Phase 1b and Phase 2) Rate of complete response (CR) [ Time Frame: Duration of each treatment cycle, 28 days ]
  4. (Phase 1b and Phase 2) Incidence and severity of adverse events (AEs) [ Time Frame: Duration of each treatment cycle, 28 days ]
  5. (Phase 1b and Phase 2) Sparse plasma concentrations for binimetinib [ Time Frame: Duration of each treatment cycle, 28 days ]


Information from the National Library of Medicine

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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

Key Inclusion Criteria

  • Measurable, histologically/cytologically confirmed metastatic colorectal cancer (mCRC).
  • Able to provide a sufficient amount of representative tumor specimen for central laboratory testing of RAS mutation status and microsatellite stable (MSS).

    • If a fresh tissue sample is provided, a blood sample is required.
  • Metastatic colorectal cancer (mCRC) categorized as microsatellite stable (MSS) by polymerase chain reaction (PCR) per local assay at any time prior to Screening or by the central laboratory.
  • RAS mutation per local assay at any time prior to Screening or by the central laboratory.
  • Have received at least 1 prior line of therapy and meets at least one of the following criteria:

    • were unable to tolerate the prior first-line regimen
    • experienced disease progression during or after prior first-line regimen for metastatic disease
    • progressed during or within 3 months of completing adjuvant chemotherapy. Note: Generally, treatments that are separated by an event of progression are considered different regimens.
  • Have received no more than 2 prior lines of therapy (maintenance therapy given in the metastatic setting will not be considered a separate regimen). Generally, treatments that are separated by an event of progression are considered different regimens.
  • Adequate bone marrow, cardiac, kidney and liver function
  • Able to take oral medications
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  • Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of child-bearing potential
  • Non-sterile male patients who are sexually active with female partners of childbearing potential must agree to follow instructions for acceptable or highly effective method(s) of contraception for the duration of study treatment and for 7 months after the last dose of study treatment with nivolumab

Key Exclusion Criteria

  • Prior treatment with any MEK inhibitor, an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Any untreated central nervous system (CNS) lesion.
  • Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Known history of retinal vein occlusion (RVO).
  • Known history of Gilbert's syndrome.
  • Pregnant or breastfeeding females.
  • Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to first day of study treatment:
  • History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli.
  • Uncontrolled hypertension defined as persistent systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite current therapy.
  • Concurrent neuromuscular disorder that is associated with the potential of elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
  • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
  • Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus.

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): NCT03271047


Locations
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United States, California
Array BioPharma Investigative Site
Encinitas, California, United States, 92024
Array BioPharma Investigative Site
Laguna Hills, California, United States, 92653
Array BioPharma Investigative Site
Santa Monica, California, United States, 90095
United States, Delaware
Array BioPharma Investigative Site
Newark, Delaware, United States, 19718
United States, Florida
Array BioPharma Investigative Sites (2)
Port Saint Lucie, Florida, United States, 34952
United States, Indiana
Array BioPharma Investigative Site
Indianapolis, Indiana, United States, 46202
United States, Missouri
Array BioPharma Investigative Site
Saint Louis, Missouri, United States, 63110
United States, Pennsylvania
Array BioPharma Investigative Sites (2)
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Array BioPharma Investigative Site
Chattanooga, Tennessee, United States, 37404
Array BioPharma Investigative Site
Nashville, Tennessee, United States, 37203
United States, Texas
Array BioPharma Investigative Site
Houston, Texas, United States, 77030
Belgium
Array BioPharma Investigative Site
Leuven, Belgium, 3000
Netherlands
Array BioPharma Investigative Site
Amsterdam, Noord-Holland, Netherlands, 1066 CX
Array BioPharma Investigative Site
Amsterdam, Noord-Holland, Netherlands, 1100 DD
Spain
Array BioPharma Investigative Site
Santander, Canabria, Spain, 39008
Array BioPharma Investigative Site
Madrid, Madrid, Communidad Delaware, Spain, 28050
Array BioPharma Investigative Site
Barcelona, Spain, 08035
Array BioPharma Investigative Site
Madrid, Spain, 28007
Array BioPharma Investigative Site
Madrid, Spain, 28041
United Kingdom
Array BioPharma Investigative Sites (2)
London, United Kingdom, SW3 6JJ
Array BioPharma Investigative Site
Oxford, United Kingdom, OX37LE
Sponsors and Collaborators
Array BioPharma
Bristol-Myers Squibb
Investigators
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Study Director: Array BioPharma, Inc Array BioPharma, Inc

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Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT03271047     History of Changes
Other Study ID Numbers: ARRAY-162-202
First Posted: September 1, 2017    Key Record Dates
Last Update Posted: July 29, 2019
Last Verified: July 2019

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

Keywords provided by Array BioPharma:
cancer

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
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents