Venetoclax and Irinotecan in Relapsed/Refractory SCLC

• Status: Withdrawn
• Trial end date: 2028-06-30
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Virginia Commonwealth University
• Collaborator: AbbVie
• Treatments: Irinotecan; Venetoclax

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