Clinical Trials /

Venetoclax and Irinotecan in Relapsed/Refractory SCLC

NCT04543916

Description:

This study is a single-arm, open-label, multicenter phase 1/2 trial designed to establish the recommended phase 2 dose (RP2D) of daily oral venetoclax when given in combination with irinotecan in patients with relapsed or refractory small cell lung cancer (SCLC).

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Venetoclax and Irinotecan in Relapsed/Refractory SCLC
  • Official Title: A Phase 1/2 Study of Venetoclax and Irinotecan in Relapsed/Refractory Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: MCC-17-13842
  • SECONDARY ID: HM20019851
  • NCT ID: NCT04543916

Conditions

  • Relapsed Small Cell Lung Cancer
  • Refractory Small Cell Lung Carcinoma

Interventions

DrugSynonymsArms
Venetoclax 50 MGDose Level 1
Venetoclax 100 MGDose Level 2
Venetoclax 200 MGDose Level 3
Venetoclax 400Dose Level 4
Venetoclax 600Dose Level 5
Irinotecan 60 mg/m2Dose Level 1
Venetoclax (RP2D)Phase 2 Expansion Cohort

Purpose

This study is a single-arm, open-label, multicenter phase 1/2 trial designed to establish the recommended phase 2 dose (RP2D) of daily oral venetoclax when given in combination with irinotecan in patients with relapsed or refractory small cell lung cancer (SCLC).

Detailed Description

      Irinotecan will be given at 60 mg/m2 on days 1, 8, and 15 of each 28-day cycle. A 3+3 dose
      escalation design will be followed until the maximum tolerated dose (MTD) of venetoclax has
      been determined. Once the MTD is established, a RP2D that is the same as or less than the MTD
      will be determined. If no RP2D can be determined, the study will close to accrual. The RP2D
      will be used in an expansion cohort based on a Simon's two-stage minimax design to evaluate
      efficacy.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Level 1ExperimentalVenetoclax 50mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
  • Venetoclax 50 MG
  • Irinotecan 60 mg/m2
Dose Level 2ExperimentalVenetoclax 100mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
  • Venetoclax 100 MG
  • Irinotecan 60 mg/m2
Dose Level 3ExperimentalVenetoclax 200mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
  • Venetoclax 200 MG
  • Irinotecan 60 mg/m2
Dose Level 4ExperimentalVenetoclax 400mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
  • Venetoclax 400
  • Irinotecan 60 mg/m2
Dose Level 5ExperimentalVenetoclax 600mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
  • Venetoclax 600
  • Irinotecan 60 mg/m2
Phase 2 Expansion CohortExperimentalVenetoclax recommended phase 2 dose (RP2D) by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
  • Irinotecan 60 mg/m2
  • Venetoclax (RP2D)

Eligibility Criteria

        Inclusion Criteria:

          -  Histological or cytological diagnosis of SCLC

          -  Disease progression or recurrence during or after platinum-based therapy, unless
             platinum-based therapy was contraindicated

          -  Phase 1: Measurable or evaluable disease according to RECIST v1.1

          -  Phase 2: Measurable disease according to RECIST v1.1

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

          -  Age ≥ 18 years

          -  Adequate bone marrow function as defined below:

               -  Absolute neutrophil count (ANC) ≥ 1,500/mm3

               -  Platelet count ≥ 100,000/mm3

               -  Hemoglobin ≥ 8.0 g/dL

          -  Adequate renal function as defined below:

          -  Serum creatinine ≤ upper limit of normal (ULN) for the lab or a calculated creatinine
             clearance ≥ 40 mL/min

          -  Adequate hepatic function as defined below:

               -  Total bilirubin ≤ 1.5 x ULN for the laboratory

               -  Aspartate aminotransferase (AST) ≤ 2.5 x ULN for the laboratory

               -  Alanine aminotransferase (ALT) ≤ 2.5 x ULN for the laboratory

          -  Persons with known HIV seropositivity are eligible if they meet the following
             criteria:

               -  CD4 count ≥ 200/mm3

               -  Undetectable HIV viral load on standard PCR-based test

               -  On a stable regimen of highly active anti-retroviral therapy (HAART) that does
                  not include protocol contraindicated agents

               -  No ongoing requirement for concurrent antibiotics or antifungal agents for the
                  prevention of HIV-associated opportunistic infections

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Ongoing requirement for any non-study anticancer therapy

          -  Ongoing or planned treatment with any of the following:

               -  Greater than 10 mg prednisone daily or equivalent

               -  Immunosuppressive agents

               -  Strong or moderate CYP3A inhibitor or inducer, or a narrow-therapeutic sensitive
                  substrate

               -  P-gp inhibitor or narrow-therapeutic sensitive P-gp substrate If any of these
                  agents have been used, patients must be off them for ≥ 1 week before initiation
                  of study treatment.

          -  Any investigational agent within 21 days prior to the first dose of the
             investigational drugs

          -  Has consumed grapefruit, grapefruit products, Seville oranges, or starfruit within 3
             days before initiation of study treatment.

          -  Phase 2 portion only: Previous systemic anticancer therapy other than platinum-based
             therapy

          -  Known leptomeningeal metastases

          -  Known untreated brain metastases

          -  Hypersensitivity to irinotecan, venetoclax, or their excipients

          -  Diarrhea ≥ grade 1

          -  Ongoing need for antidiarrheal agents

          -  Active uncontrolled infection, ongoing or within 2 weeks before initiating treatment

          -  Known homozygosity for the UGT1A1*28 allele Note: Study-specific UGT1A1 testing is not
             required

          -  Inability to swallow oral medications and/or malabsorption

          -  Pregnancy or breastfeeding

          -  Medical, psychological, or social condition that, in the opinion of the investigator,
             may increase the patient's risk or limit the patient's adherence with study
             requirements
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Determine the recommended phase 2 dose (RP2D) of venetoclax with irinotecan in patients with relapsed or refractory SCLC
Time Frame:90 Days
Safety Issue:
Description:Recommended phase 2 dose (RP2D) of venetoclax in combination with irinotecan that is less than or equal to the maximum tolerated dose (MTD). A 3+3 dose escalation design will be followed until the maximum tolerated dose (MTD) of venetoclax has been determined. Patients assigned to a dose level of venetoclax greater than 50 mg will undergo a ramp-up phase during the first week of irinotecan

Secondary Outcome Measures

Measure:Assess the frequency of adverse events (AEs)
Time Frame:120 Days
Safety Issue:
Description:Assess adverse events (AEs) characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE V 5.0) to determine safety and toxicity of the combination of venetoclax and irinotecan.
Measure:Evaluate the antitumor effects of venetoclax and irinotecan in combination.
Time Frame:180 Days
Safety Issue:
Description:Evaluate the anti tumor effects of tumor response based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
Measure:Observe survival in relapsed or refractory SCLC patients receiving venetoclax in combination with irinotecan
Time Frame:180 Days
Safety Issue:
Description:Progression-free survival and overall survival of patients with relapsed or refractory SCLC receiving venetoclax in combination with irinotecan

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Virginia Commonwealth University

Trial Keywords

  • Relapsed SCLC
  • Refractory SCLC

Last Updated

September 2, 2020