NCT04543916

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).

Trial Health

45
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Timeline
26mo left

Started Jun 2021

Longer than P75 for phase_1

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress69%
Jun 2021Jun 2028

First Submitted

Initial submission to the registry

September 2, 2020

Completed
8 days until next milestone

First Posted

Study publicly available on registry

September 10, 2020

Completed
10 months until next milestone

Study Start

First participant enrolled

June 30, 2021

Completed
6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 30, 2028

Expected
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2028

Last Updated

March 3, 2021

Status Verified

March 1, 2021

Enrollment Period

6.9 years

First QC Date

September 2, 2020

Last Update Submit

March 1, 2021

Conditions

Relapsed Small Cell Lung CancerRefractory Small Cell Lung Carcinoma

Keywords

Relapsed SCLCRefractory SCLC

Outcome Measures

Primary Outcomes (2)

  • 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

    90 Days

  • 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.

    180 Days

Secondary Outcomes (3)

  • Assess the frequency of adverse events (AEs)

    120 Days

  • Evaluate the antitumor effects of venetoclax and irinotecan in combination.

    180 Days

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

    180 Days

Study Arms (6)

Dose Level 1

EXPERIMENTAL

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

Drug: Venetoclax 50 MGDrug: 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

Drug: Venetoclax 100 MGDrug: 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

Drug: Venetoclax 200 MGDrug: 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

Drug: Venetoclax 400Drug: 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

Drug: Venetoclax 600Drug: 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

Drug: Irinotecan 60 mg/m2Drug: Venetoclax (RP2D)

Interventions

Venetoclax 50 MGDRUG

Escalating doses to determine recommended phase 2 dose (RP2D)

Dose Level 1
Venetoclax 100 MGDRUG

Escalating doses to determine recommended phase 2 dose (RP2D)

Dose Level 2
Venetoclax 200 MGDRUG

Escalating doses to determine recommended phase 2 dose (RP2D)

Dose Level 3
Venetoclax 400DRUG

Escalating doses to determine recommended phase 2 dose (RP2D)

Dose Level 4
Venetoclax 600DRUG

Escalating doses to determine recommended phase 2 dose (RP2D)

Dose Level 5
Irinotecan 60 mg/m2DRUG

Intravenously (IV), days 1, 8, and 15

Dose Level 1Dose Level 2Dose Level 3Dose Level 4Dose Level 5Phase 2 Expansion Cohort
Venetoclax (RP2D)DRUG

orally, once per day

Phase 2 Expansion Cohort

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +7 more criteria

You may not qualify if:

  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

venetoclaxIrinotecan

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

CamptothecinAlkaloidsHeterocyclic Compounds

Study Officials

  • Sosipatros Boikos, MD

    Massey Cancer Center

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Dose escalation will proceed within each cohort. Phase II is the expansion cohort at the recommended phase 2 dose found in phase 1
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 2, 2020

First Posted

September 10, 2020

Study Start

June 30, 2021

Primary Completion (Estimated)

May 30, 2028

Study Completion (Estimated)

June 30, 2028

Last Updated

March 3, 2021

Record last verified: 2021-03