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Study of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT03711058
Recruitment Status : Recruiting
First Posted : October 18, 2018
Last Update Posted : October 19, 2020
Sponsor:
Collaborators:
Bayer
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE October 15, 2018
First Posted Date  ICMJE October 18, 2018
Last Update Posted Date October 19, 2020
Actual Study Start Date  ICMJE January 10, 2019
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 15, 2018)
  • Determine maximum tolerated dose (MTD) of copanlisib with fixed dose nivolumab [ Time Frame: 2 years ]
    Number of patients having a dose limiting toxicities (DLT) at each level.
  • 6-month objective response rate (ORR) of patients treated with copanlisib and nivolumab [ Time Frame: 6-months ]
    The proportion of subjects with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2018)
  • Disease control rate (DCR) status at 6 months. [ Time Frame: 6-months ]
    Percentage of participants achieving stable disease (SD) or better (SD + partial response (PR) + (CR).
  • Duration of response (DOR) status at 6 months. [ Time Frame: 6-months ]
    Number of months from the first documentation of a response to date of disease progression.
  • Progression free survival (PFS) status at 6 months. [ Time Frame: 6-months ]
    Number of months from treatment to disease progression (PD)
  • Overall survival (OS) status at 6 months. [ Time Frame: 6-months ]
    Number of months from the date of first treatment until death or end of follow-up.
  • Number of participants experiencing study drug-related toxicities [ Time Frame: 2 years ]
    Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer
Official Title  ICMJE A Phase I/II Study of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer
Brief Summary A phase I/II study of PI3Kinase inhibition (copanlisib) and anti-PD-1 antibody nivolumab in relapsed/refractory solid tumors with expansions in mismatch-repair proficient (MSS) colorectal cancer.
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
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor Along With Microsatellite Stable (MSS) Colon Cancer
  • Colon Cancer
Intervention  ICMJE
  • Drug: Copanlisib

    Copanlisib will be administered as a 60 minute IV infusion (-5min/+10min) at a dose of 45 mg - 60 mg IV. Copanlisib will be administered once a week (days 1, 8, and 15 or Day 1 and Day 15 of each 28 day cycle).

    Drug: 45 or 60 mg IV

    Other Name: Bay 80-6946
  • Drug: Nivolumab

    Nivolumab 480 mg will be administered as a 30 minute IV infusion (-5min/+10min) on Day 1 of each 28 day cycle.

    Drug: 480 mg IV

    Other Name: OPDIVO, Bay 80-6946
Study Arms  ICMJE
  • Experimental: Phase I - Copanlisib and Nivolumab (De-Escalation)
    Interventions:
    • Drug: Copanlisib
    • Drug: Nivolumab
  • Experimental: Phase II - Copanlisib and Nivolumab
    Interventions:
    • Drug: Copanlisib
    • Drug: Nivolumab
Publications * Morschhauser F, Machiels JP, Salles G, Rottey S, Rule SAJ, Cunningham D, Peyrade F, Fruchart C, Arkenau HT, Genvresse I, Liu L, Köchert K, Shen K, Kneip C, Peña CE, Grevel J, Zhang J, Cisternas G, Reschke S, Granvil C, Awada A. On-Target Pharmacodynamic Activity of the PI3K Inhibitor Copanlisib in Paired Biopsies from Patients with Malignant Lymphoma and Advanced Solid Tumors. Mol Cancer Ther. 2020 Feb;19(2):468-478. doi: 10.1158/1535-7163.MCT-19-0466. Epub 2019 Oct 16.

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 15, 2018)
54
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥18 years.
  • Ability to understand and willingness to sign a written informed consent document.
  • Phase I: Must have received all curative treatment options and at least 2 lines of systemic therapy.
  • Phase II: Must have received at least 2 lines of systemic therapy including a fluropyrimidine, oxaliplatin, and irinotecan-containing regimen. KRAS/NRAS/BRAF wildtype patients must have received or refused anti-EGR.
  • Must have received all curative treatment options and at least 2 lines of systemic and standard therapy.
  • Must have measurable disease based on RECIST 1.1
  • Must have biopsiable disease.
  • ECOG performance status 0 or 1
  • Life expectancy of greater than 3 months.
  • Patients must have adequate organ and marrow function defined by study-specified laboratory tests within 21 days of initial study drug.
  • Men must use acceptable form of birth control while on study.
  • Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.

Exclusion Criteria:

  • Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti- PD-L2, anti-CTLA4, etc.).
  • Prior therapy with a PI3K inhibitor
  • Chemotherapy, target small molecule therapy, investigational therapy, or surgery within 4 weeks prior to first dose of treatment.
  • Has received prior radiotherapy within 2 weeks prior to the start of treatment.
  • Patient who is receiving or have received any other investigational agents within 4 weeks prior to the first dose of treatment.
  • Has received a live vaccine 30 days prior to the first dose of study drug.
  • Has known additional malignancy that is progressing or requires active treatment..
  • Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has symptomatic ascites or has required a paracentesis in the last 12 weeks.
  • Hypersensitivity reaction to study drug.
  • Patients diagnosed of immunodeficiency or are on any immunosuppressive agents within 7 days prior to first dose of study drug.
  • Has active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Infection with HIV or hepatitis B or C.
  • CMV PCR (cytomegalovirus polymerase chain reaction) positive.
  • Known history or concurrent interstitial lung disease.
  • Type I diabetes or Type II diabetes requiring treatment with a sulfonylurea, meglitinide, or insulin at screening.
  • Uncontrolled cardiovascular disease.
  • Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Use of anti-arrhythmic therapy (beta blockers or digoxin are permitted).
  • Use of CYP3A4 inhibitors and inducers within 2 weeks of starting study drug and throughout treatment.
  • Any arterial or venous thrombotic or embolic events within 3 months of start of study drug.
  • Non-healing wound, ulcer, or fracture.
  • Patients with evidence or history of bleeding condition.
  • Had a blood or platelet transfusion within 7 days of Cycle 1 Day 1 treatment.
  • Seizure disorder requiring anti-seizure medication.
  • Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures.
  • Are pregnant or breastfeeding.
  • Unwilling or unable to follow the study schedule for any reason.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Susan Sartorius-Mergenthaler, RN 410-614-3644 Sartosu@jhmi.edu
Contact: Joann Santmyer, RN 410-583-2970 jsantmy1@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03711058
Other Study ID Numbers  ICMJE J1887
IRB00175864 ( Other Identifier: JHM IRB )
CA209-8LC ( Other Identifier: Bristol-Myers Squibb )
Has Data Monitoring Committee Yes
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: Undecided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE
  • Bayer
  • Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Nilofer Azad, MD Johns Hopkins Medical Institution
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date October 2020

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