Venetoclax and Irinotecan in Relapsed/Refractory SCLC

March 1, 2021 updated by: Virginia Commonwealth University

A Phase 1/2 Study of Venetoclax and Irinotecan in Relapsed/Refractory Small Cell Lung Cancer

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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: Irinotecan 60 mg/m2
Intravenously (IV), days 1, 8, and 15
Drug: Venetoclax 100 MG
Escalating doses to determine recommended phase 2 dose (RP2D)
Experimental: Dose Level 3
Venetoclax 200mg 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 200 MG
Escalating doses to determine recommended phase 2 dose (RP2D)
Experimental: Dose Level 4
Venetoclax 400mg 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 400
Escalating doses to determine recommended phase 2 dose (RP2D)
Experimental: Dose Level 5
Venetoclax 600mg 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 600
Escalating doses to determine recommended phase 2 dose (RP2D)
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
90 Days
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.
180 Days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
120 Days
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).
180 Days
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
180 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Virginia Commonwealth University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
AbbVie

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sosipatros Boikos, MD, Massey Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 30, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 30, 2028

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 2, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 3, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MCC-17-13842
  • HM20019851 (Other Identifier: Virginia Commonwealth University Massey Cancer Center)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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