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

NCT03271047

Last updated date
Study Location
Pfizer Investigative Site
Encinitas, California, 92024, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
MSS, RAS-mutant Colorectal Cancer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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.

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MSS, RAS-mutant Colorectal CancerStudy of Binimetinib + Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer With RAS Mutation
NCT03271047
  1. Encinitas, California
  2. Laguna Hills, California
  3. Santa Monica, California
  4. Newark, Delaware
  5. Port Saint Lucie, Florida
  6. Indianapolis, Indiana
  7. Saint Louis, Missouri
  8. Philadelphia, Pennsylvania
  9. Chattanooga, Tennessee
  10. Nashville, Tennessee
  11. Houston, Texas
  12. Leuven,
  13. Amsterdam, Noord-Holland
  14. Amsterdam, Noord-Holland
  15. Santander, Canabria
  16. Madrid, Madrid, Communidad Delaware
  17. Barcelona,
  18. Madrid,
  19. Madrid,
  20. London,
  21. Oxford,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Study of Binimetinib + Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer With RAS Mutation
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • MSS
  • RAS-mutant Colorectal Cancer
Intervention  ICMJE
  • Drug: binimetinib
    Orally, twice daily.
  • Drug: nivolumab
    Intravenously (IV) every 4 weeks (Q4W)
  • Drug: ipilimumab
    intravenously (IV) every 8 weeks (Q8W)
Study Arms  ICMJE
  • Experimental: Phase 1b / Arm 1A
    binimetinib + nivolumab
    Interventions:
    • Drug: binimetinib
    • Drug: nivolumab
  • Experimental: Phase 1b / Arm 1B
    binimetinib + nivolumab + ipilimumab
    Interventions:
    • Drug: binimetinib
    • Drug: nivolumab
    • Drug: ipilimumab
  • Experimental: Phase 2 / Arm 2A
    binimetinib + nivolumab
    Interventions:
    • Drug: binimetinib
    • Drug: nivolumab
  • Experimental: Phase 2 / Arm 2B
    binimetinib + nivolumab + ipilimumab
    Interventions:
    • Drug: binimetinib
    • Drug: nivolumab
    • Drug: ipilimumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 31, 2017)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 21, 2021
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03271047
Other Study ID Numbers  ICMJE ARRAY-162-202
C4211004 ( Other Identifier: Pfizer )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d….
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d…
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP