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Venetoclax and Irinotecan in Relapsed/Refractory SCLC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04543916
Recruitment Status : Withdrawn (AbbVie decided to stop trial involving Venetoclax for safety measures needed)
First Posted : September 10, 2020
Last Update Posted : March 3, 2021
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Virginia Commonwealth University

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Relapsed Small Cell Lung Cancer Refractory Small Cell Lung Carcinoma Drug: Venetoclax 50 MG Drug: Venetoclax 100 MG Drug: Venetoclax 200 MG Drug: Venetoclax 400 Drug: Venetoclax 600 Drug: Irinotecan 60 mg/m2 Drug: Venetoclax (RP2D) Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation will proceed within each cohort. Phase II is the expansion cohort at the recommended phase 2 dose found in phase 1
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Venetoclax and Irinotecan in Relapsed/Refractory Small Cell Lung Cancer
Estimated Study Start Date : June 30, 2021
Estimated Primary Completion Date : May 30, 2028
Estimated Study Completion Date : June 30, 2028


Arm Intervention/treatment
Experimental: Dose Level 1
Venetoclax 50mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
Drug: Venetoclax 50 MG
Escalating doses to determine recommended phase 2 dose (RP2D)

Drug: Irinotecan 60 mg/m2
Intravenously (IV), days 1, 8, and 15

Experimental: Dose Level 2
Venetoclax 100mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
Drug: Venetoclax 100 MG
Escalating doses to determine recommended phase 2 dose (RP2D)

Drug: Irinotecan 60 mg/m2
Intravenously (IV), days 1, 8, and 15

Experimental: Dose Level 3
Venetoclax 200mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
Drug: Venetoclax 200 MG
Escalating doses to determine recommended phase 2 dose (RP2D)

Drug: Irinotecan 60 mg/m2
Intravenously (IV), days 1, 8, and 15

Experimental: Dose Level 4
Venetoclax 400mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
Drug: Venetoclax 400
Escalating doses to determine recommended phase 2 dose (RP2D)

Drug: Irinotecan 60 mg/m2
Intravenously (IV), days 1, 8, and 15

Experimental: Dose Level 5
Venetoclax 600mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
Drug: Venetoclax 600
Escalating doses to determine recommended phase 2 dose (RP2D)

Drug: Irinotecan 60 mg/m2
Intravenously (IV), days 1, 8, and 15

Experimental: Phase 2 Expansion Cohort
Venetoclax recommended phase 2 dose (RP2D) by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15
Drug: Irinotecan 60 mg/m2
Intravenously (IV), days 1, 8, and 15

Drug: Venetoclax (RP2D)
orally, once per day




Primary Outcome Measures :
  1. Phase 1: Determine the recommended phase 2 dose (RP2D) of venetoclax with irinotecan in patients with relapsed or refractory SCLC [ Time Frame: 90 Days ]
    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

  2. Phase 2: Evaluate the efficacy of venetoclax with irinotecan in patients with relapsed or refractory SCLC [ Time Frame: 180 Days ]
    The RP2D will be used in an expansion cohort based on a Simon's two-stage minimax design to evaluate efficacy.


Secondary Outcome Measures :
  1. Assess the frequency of adverse events (AEs) [ Time Frame: 120 Days ]
    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.

  2. Evaluate the antitumor effects of venetoclax and irinotecan in combination. [ Time Frame: 180 Days ]
    Evaluate the anti tumor effects of tumor response based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).

  3. Observe survival in relapsed or refractory SCLC patients receiving venetoclax in combination with irinotecan [ Time Frame: 180 Days ]
    Progression-free survival and overall survival of patients with relapsed or refractory SCLC receiving venetoclax in combination with irinotecan



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT04543916


Sponsors and Collaborators
Virginia Commonwealth University
AbbVie
Investigators
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Principal Investigator: Sosipatros Boikos, MD Massey Cancer Center
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Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT04543916    
Other Study ID Numbers: MCC-17-13842
HM20019851 ( Other Identifier: Virginia Commonwealth University Massey Cancer Center )
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: March 3, 2021
Last Verified: March 2021

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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 Virginia Commonwealth University:
Relapsed SCLC
Refractory SCLC
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Irinotecan
Venetoclax
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents