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Venetoclax and Irinotecan in Relapsed/Refractory SCLC

Primary Purpose

Relapsed Small Cell Lung Cancer, Refractory Small Cell Lung Carcinoma

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Venetoclax 50 MG

Venetoclax 100 MG

Venetoclax 200 MG

Venetoclax 400

Venetoclax 600

Irinotecan 60 mg/m2

Venetoclax (RP2D)

About this trial

This is an interventional treatment trial for Relapsed Small Cell Lung Cancer focused on measuring Relapsed SCLC, Refractory SCLC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Dose Level 1

Dose Level 2

Dose Level 3

Dose Level 4

Dose Level 5

Phase 2 Expansion Cohort

Arm Description

Venetoclax 50mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Venetoclax 100mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Venetoclax 200mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Venetoclax 400mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Venetoclax 600mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Venetoclax recommended phase 2 dose (RP2D) by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Outcomes

Primary Outcome Measures

Phase 1: Determine the recommended phase 2 dose (RP2D) of venetoclax with irinotecan in patients with relapsed or refractory SCLC

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

Phase 2: Evaluate the efficacy of venetoclax with irinotecan in patients with relapsed or refractory SCLC

The RP2D will be used in an expansion cohort based on a Simon's two-stage minimax design to evaluate efficacy.

Secondary Outcome Measures

Assess the frequency of adverse events (AEs)

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.

Evaluate the antitumor effects of venetoclax and irinotecan in combination.

Evaluate the anti tumor effects of tumor response based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).

Observe survival in relapsed or refractory SCLC patients receiving venetoclax in combination with irinotecan

Progression-free survival and overall survival of patients with relapsed or refractory SCLC receiving venetoclax in combination with irinotecan

Full Information

NCT ID

NCT04543916

First Posted

September 2, 2020

Last Updated

March 1, 2021

Sponsor

Virginia Commonwealth University

Collaborators

AbbVie

1. Study Identification

Unique Protocol Identification Number

NCT04543916

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Withdrawn

Why Stopped

AbbVie decided to stop trial involving Venetoclax for safety measures needed

Study Start Date

June 30, 2021 (Anticipated)

Primary Completion Date

May 30, 2028 (Anticipated)

Study Completion Date

June 30, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Virginia Commonwealth University

Collaborators

AbbVie

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapsed Small Cell Lung Cancer, Refractory Small Cell Lung Carcinoma

Keywords

Relapsed SCLC, Refractory SCLC

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

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)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose Level 1

Arm Type

Experimental

Arm Description

Venetoclax 50mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Arm Title

Dose Level 2

Arm Type

Experimental

Arm Description

Venetoclax 100mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Arm Title

Dose Level 3

Arm Type

Experimental

Arm Description

Venetoclax 200mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Arm Title

Dose Level 4

Arm Type

Experimental

Arm Description

Venetoclax 400mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Arm Title

Dose Level 5

Arm Type

Experimental

Arm Description

Venetoclax 600mg by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Arm Title

Phase 2 Expansion Cohort

Arm Type

Experimental

Arm Description

Venetoclax recommended phase 2 dose (RP2D) by mouth once daily and Irinotecan 60 mg/m2 intravenously (IV) on days 1, 8, and 15

Intervention Type

Drug

Intervention Name(s)

Venetoclax 50 MG

Intervention Description