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).
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
Drug | Synonyms | Arms |
---|
Venetoclax 50 MG | | Dose Level 1 |
Venetoclax 100 MG | | Dose Level 2 |
Venetoclax 200 MG | | Dose Level 3 |
Venetoclax 400 | | Dose Level 4 |
Venetoclax 600 | | Dose Level 5 |
Irinotecan 60 mg/m2 | | Dose 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
Name | Type | Description | Interventions |
---|
Dose Level 1 | Experimental | Venetoclax 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 2 | Experimental | Venetoclax 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 3 | Experimental | Venetoclax 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 4 | Experimental | Venetoclax 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 5 | Experimental | Venetoclax 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 Cohort | Experimental | Venetoclax 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: | Withdrawn |
Lead Sponsor: | Virginia Commonwealth University |
Trial Keywords
- Relapsed SCLC
- Refractory SCLC
Last Updated
March 3, 2021