- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03711058
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
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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
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Baltimore, Maryland, United States, 21231
- Sidney Kimmel Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 fluoropyrimidine, 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.
- Eastern Cooperative Oncology Group (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.
- Cytomegalovirus polymerase chain reaction (CMV PCR) 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase I - Copanlisib and Nivolumab (De-Escalation)
|
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 Names:
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 Names:
|
Experimental: Phase II /Arm A-P13K mutation/Copanlisib and Nivolumab
|
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 Names:
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 Names:
|
Experimental: Phase II/Arm B -P13K wild type /Copanlisib and Nivolumab
|
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 Names:
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Experiencing a Dose Limiting Toxicity
Time Frame: 28 days
|
Number of participants experiencing a Dose Limiting Toxicity (DLT) in each dose level. DLT is defined as any of the following study drug-related toxicities occurring during the first cycle of study drug on study:
|
28 days
|
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).
Per RECIST 1.1, complete response is defined as disappearance of all target lesions, and partial response is defined as at least a 30% decrease in the sum of diameters of target lesions.
Lesions are assessed by CT or MRI.
|
6-months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Control Rate (DCR) Status at 6 Months.
Time Frame: 6-months
|
Percentage of participants achieving stable disease (SD) or better (SD + PR + CR). Per RECIST 1.1, complete response is defined as disappearance of all target lesions, partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, stable disease occurs when there is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least 20% increase). Lesions are assessed by CT or MRI. |
6-months
|
Duration of Response (DOR)
Time Frame: 2 years
|
Number of months from the first documentation of a response to date of disease progression.
|
2 years
|
Progression Free Survival (PFS)
Time Frame: 2 years
|
Number of months from treatment to disease progression (PD)
|
2 years
|
Overall Survival (OS)
Time Frame: 2 years
|
Number of months from the date of first treatment until death or end of follow-up.
|
2 years
|
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.
|
2 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Nilofer Azad, MD, Johns Hopkins Medical Institution
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Colorectal Neoplasms
- Colonic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
Other Study ID Numbers
- J1887
- IRB00175864 (Other Identifier: JHM IRB)
- CA209-8LC (Other Identifier: Bristol-Myers Squibb)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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