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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 : July 25, 2019
Sponsor:
Collaborators:
Bayer
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor Along With Microsatellite Stable (MSS) Colon Cancer Colon Cancer Drug: Copanlisib Drug: Nivolumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 10, 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase I - Copanlisib and Nivolumab (De-Escalation) 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 60 minute IV infusion (-5min/+10min) on Day 1 of each 28 day cycle.

Drug: 480 mg IV

Other Name: OPDIVO, Bay 80-6946

Experimental: Phase II - Copanlisib and Nivolumab 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 60 minute IV infusion (-5min/+10min) on Day 1 of each 28 day cycle.

Drug: 480 mg IV

Other Name: OPDIVO, Bay 80-6946




Primary Outcome Measures :
  1. 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.

  2. 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)


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. Progression free survival (PFS) status at 6 months. [ Time Frame: 6-months ]
    Number of months from treatment to disease progression (PD)

  4. 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.

  5. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years.
  • Ability to understand and willingness to sign a written informed consent document.
  • Have histologically metastatic or unresectable microsatellite stable (MSS) solid tumor cancer or microsatellite stable MSS colon cancer.
  • 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 P13K inhibitor
  • Chemotherapy, radiotherapy, 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 progressive disease or 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.
  • HbA1c >8.5% at screening.
  • 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.
  • 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.

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): NCT03711058


Contacts
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Contact: Susan Sartorius-Mergenthaler, RN 410-614-3644 Sartosu@jhmi.edu
Contact: Ellen Lilly-Foreman, RN 443-287-4961 lillyel@jhmi.edu

Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Susan Sartorius-Mergenthaler, RN    410-614-3644    Sartosu@jhmi.edu   
Contact: Ellen Lilly-Foreman, RN    443-287-4961    lillyel@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Bayer
Bristol-Myers Squibb
Investigators
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Principal Investigator: Nilofer Azad, MD Johns Hopkins Medical Institution

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03711058     History of Changes
Other Study ID Numbers: J1887
IRB00175864 ( Other Identifier: JHM IRB )
CA209-8LC ( Other Identifier: Bristol-Myers Squibb )
First Posted: October 18, 2018    Key Record Dates
Last Update Posted: July 25, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Immunotherapy
Nivolumab
Copanlisib
Unresectable
Metastatic
PD-1
P13K
Antibody
Solid Tumors
Colon Cancer
MSS
Mismatch-repair proficient
Microsatellite stable
Additional relevant MeSH terms:
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Colonic Neoplasms
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Nivolumab
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents