Clinical Trials /

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

NCT03711058

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: J1887
  • SECONDARY ID: IRB00175864
  • SECONDARY ID: CA209-8LC
  • NCT ID: NCT03711058

Conditions

  • Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor Along With Microsatellite Stable (MSS) Colon Cancer
  • Colon Cancer

Interventions

DrugSynonymsArms
CopanlisibBay 80-6946Phase I - Copanlisib and Nivolumab (De-Escalation)
NivolumabOPDIVO, Bay 80-6946Phase I - Copanlisib and Nivolumab (De-Escalation)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase I - Copanlisib and Nivolumab (De-Escalation)Experimental
  • Copanlisib
  • Nivolumab
Phase II - Copanlisib and NivolumabExperimental
  • Copanlisib
  • Nivolumab

Eligibility 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.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine maximum tolerated dose (MTD) of copanlisib with fixed dose nivolumab
Time Frame:2 years
Safety Issue:
Description:Number of patients having a dose limiting toxicities (DLT) at each level.

Secondary Outcome Measures

Measure:Disease control rate (DCR) status at 6 months.
Time Frame:6-months
Safety Issue:
Description:Percentage of participants achieving stable disease (SD) or better (SD + partial response (PR) + (CR).
Measure:Duration of response (DOR) status at 6 months.
Time Frame:6-months
Safety Issue:
Description:Number of months from the first documentation of a response to date of disease progression.
Measure:Progression free survival (PFS) status at 6 months.
Time Frame:6-months
Safety Issue:
Description:Number of months from treatment to disease progression (PD)
Measure:Overall survival (OS) status at 6 months.
Time Frame:6-months
Safety Issue:
Description:Number of months from the date of first treatment until death or end of follow-up.
Measure:Number of participants experiencing study drug-related toxicities
Time Frame:2 years
Safety Issue:
Description:Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • Immunotherapy
  • Nivolumab
  • Copanlisib
  • Unresectable
  • Metastatic
  • PD-1
  • P13K
  • Antibody
  • Solid Tumors
  • Colon Cancer
  • MSS
  • Mismatch-repair proficient
  • Microsatellite stable

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