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Talazoparib and Thoracic RT for ES-SCLC

Primary Purpose

Lung Cancer, Small-Cell Lung Cancer

Status
Recruiting
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Talazoparib in Combination with Low Dose Radiotherapy (RT)
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring Talazoparib, Thoracic Radiotherapy, Chemotherapy

Eligibility Criteria

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

Inclusion Criteria:

  • Histological documented diagnosis of SCLC confirmed by a UHN pathologist.
  • Documented extensive disease
  • Completion of induction chemotherapy, 4-6 cycles of a platinum agent and etoposide.
  • No disease progression (i.e.SD or better response by RECIST 1.1) at the completion of chemotherapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnosfsky Performance Score (KPS) ≥50; see Appendix B).
  • Adequate organ and marrow function,
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.

Exclusion Criteria:

  • Untreated brain metastases.
  • Previous radiotherapy to thorax (prior breast RT is permitted).
  • Patients receiving any systemic chemotherapy, radiotherapy or immunotherapy (except for standard of care treatments or palliative reasons) within 3 weeks prior to study treatment.
  • Exposure to an investigational product within 30 days or 5 half-lives (whichever is longer) prior to start of the current study drug.
  • Any previous treatment with PARP inhibitor, including talazoparib.
  • Concomitant use of strong P-gp inhibitors
  • Concomitant use of other known P-gp inhibitors, P-gp inducers, or BCRP inhibitors
  • Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
  • Patients with myelodysplastic syndrome/acute leukaemia or with features suggestive thereof.
  • Major surgery within 2 weeks of study treatment initiation and patients must have recovered from any effects of any major surgery.
  • Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active/uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
  • Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Immunocompromised patients,
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
  • Whole blood transfusions in the last 120 days prior to entry to the study
  • Other malignancy within the last 5 years
  • Patients with spinal cord compression

Sites / Locations

  • Princess Margaret Cancer Center, University Health NetworkRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Talazoparib in Combination with Low Dose RT

Arm Description

Patients will start on talazoparib on day 1 of study intervention, and will continue to orally take talazoparib until the last day of RT (until day 20-23). Patient will start low dose RT on day 6-9, and will continue for 10 fractions throughout 2 weeks. Talazoparib dose levels will start at 0.5mg daily and increase to 1mg if dose limiting toxicites are not observed. Toxicities include renal impairment and other treatment related toxicities Grade ≥3. Patients will be monitored weekly during study treatment, and followed up at 3 weeks, and every 3 months after for 1 year.

Outcomes

Primary Outcome Measures

Safety of Talazoparib in Combination with Low Dose Thoracic Radiotherapy
Safety will be measured by assessing all adverse events as determined by the investigator using CTCAE v.5.0.
Maximum Tolerated Dose (MTD) of Talazoparib in Combination with Low Dose Thoracic Radiotherapy
MTD will be defined as the maximum dose by a standard 3+3 design

Secondary Outcome Measures

Loco-regional Recurrence
Loco-regional recurrence will be assessed by using RECIST v1.1 criteria
Progression-Free Survival (PFS)
PFS will be defined as the time of start of radiotherapy to first local/loco-regional or distance recurrence event, or death.
Overall Survival (OS)
OS will be defined as the time from the start of radiotherapy to death from any cause.
Acute Toxicities
Acute toxicities will be assessed by physician-graded CTCAE.
Chronic Toxicities
Chronic toxicities will be assessed by physician-graded CTCAE.

Full Information

First Posted
November 18, 2019
Last Updated
April 5, 2023
Sponsor
University Health Network, Toronto
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT04170946
Brief Title
Talazoparib and Thoracic RT for ES-SCLC
Official Title
A Phase I Study of Talazoparib and Consolidative Thoracic Radiotherapy for Extensive Stage Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 5, 2020 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
Collaborators
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase I, dose escalating study evaluating the safety of combining talazoparib and low dose consolidative thoracic radiotherapy for small cell lung cancer patients. This study will also determine the maximum tolerated dose (MTD) of talazoparib in combination with low dose thoracic radiotherapy. Patients will start on talazoparib on day 1 of study intervention, and will continue to orally take talazoparib until the last day of radiation therapy. Up to 24 patients will be enrolled to the study, where the first 3 patients will start with a starting dose level of talazoparib is 0.5 mg PO once daily. This will increase to 1mg daily with each new cohort.
Detailed Description
This is a phase I, dose escalating study evaluating the safety of combination talazoparib and low dose consolidative thoracic radiotherapy for extensive-stage small cell lung cancer patients with at least stable disease after standard of care 4 - 6 cycles of chemotherapy (a platinum agent and etoposide). This study will also determine the maximum tolerated dose (MTD) of talazoparib in combination with low dose thoracic radiotherapy. Secondary objectives will be to examine clinical outcomes, including locoregional recurrence within the radiation field, progression-free survival, overall survival and acute/chronic toxicities up to 1 year. Patients will start on talazoparib on day 1 of study intervention, and will continue to orally take talazoparib until the last day of RT. Patient will start low dose RT on day 6-9, and will continue for 10 fractions throughout 2 weeks. Up to 24 patients will be enrolled to the study, where the first 3 patients will start with a starting dose level of talazoparib is 0.5 mg PO once daily. This will increase to 1mg daily with each new cohort. Patients will be monitored weekly during study treatment, and followed up at 3 weeks, and every 3 months after for 1 year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer, Small-Cell Lung Cancer
Keywords
Talazoparib, Thoracic Radiotherapy, Chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Dose escalation based on the maximum tolerated dose from each previous cohort within the study.
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Talazoparib in Combination with Low Dose RT
Arm Type
Experimental
Arm Description
Patients will start on talazoparib on day 1 of study intervention, and will continue to orally take talazoparib until the last day of RT (until day 20-23). Patient will start low dose RT on day 6-9, and will continue for 10 fractions throughout 2 weeks. Talazoparib dose levels will start at 0.5mg daily and increase to 1mg if dose limiting toxicites are not observed. Toxicities include renal impairment and other treatment related toxicities Grade ≥3. Patients will be monitored weekly during study treatment, and followed up at 3 weeks, and every 3 months after for 1 year.
Intervention Type
Other
Intervention Name(s)
Talazoparib in Combination with Low Dose Radiotherapy (RT)
Intervention Description
Dose escalation model to determine the safety and MTD of talazoparib in combination with low dose RT.
Primary Outcome Measure Information:
Title
Safety of Talazoparib in Combination with Low Dose Thoracic Radiotherapy
Description
Safety will be measured by assessing all adverse events as determined by the investigator using CTCAE v.5.0.
Time Frame
Up to 3 years upon enrollment
Title
Maximum Tolerated Dose (MTD) of Talazoparib in Combination with Low Dose Thoracic Radiotherapy
Description
MTD will be defined as the maximum dose by a standard 3+3 design
Time Frame
Up to 1 year
Secondary Outcome Measure Information:
Title
Loco-regional Recurrence
Description
Loco-regional recurrence will be assessed by using RECIST v1.1 criteria
Time Frame
6 months and 1 year
Title
Progression-Free Survival (PFS)
Description
PFS will be defined as the time of start of radiotherapy to first local/loco-regional or distance recurrence event, or death.
Time Frame
6 months and 1 year
Title
Overall Survival (OS)
Description
OS will be defined as the time from the start of radiotherapy to death from any cause.
Time Frame
6 months and 1 year
Title
Acute Toxicities
Description
Acute toxicities will be assessed by physician-graded CTCAE.
Time Frame
Up to 1 year
Title
Chronic Toxicities
Description
Chronic toxicities will be assessed by physician-graded CTCAE.
Time Frame
Up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histological documented diagnosis of SCLC confirmed by a UHN pathologist. Documented extensive disease Completion of induction chemotherapy, 4-6 cycles of a platinum agent and etoposide. No disease progression (i.e.SD or better response by RECIST 1.1) at the completion of chemotherapy. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnosfsky Performance Score (KPS) ≥50; see Appendix B). Adequate organ and marrow function, Postmenopausal or evidence of non-childbearing status for women of childbearing potential negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Exclusion Criteria: Untreated brain metastases. Previous radiotherapy to thorax (prior breast RT is permitted). Patients receiving any systemic chemotherapy, radiotherapy or immunotherapy (except for standard of care treatments or palliative reasons) within 3 weeks prior to study treatment. Exposure to an investigational product within 30 days or 5 half-lives (whichever is longer) prior to start of the current study drug. Any previous treatment with PARP inhibitor, including talazoparib. Concomitant use of strong P-gp inhibitors Concomitant use of other known P-gp inhibitors, P-gp inducers, or BCRP inhibitors Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia. Patients with myelodysplastic syndrome/acute leukaemia or with features suggestive thereof. Major surgery within 2 weeks of study treatment initiation and patients must have recovered from any effects of any major surgery. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active/uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. Immunocompromised patients, Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT). Whole blood transfusions in the last 120 days prior to entry to the study Other malignancy within the last 5 years Patients with spinal cord compression
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Benjamin Lok, MD
Phone
416-946-4501
Ext
5819
Email
Benjamin.Lok@rmp.uhn.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin Lok, MD
Organizational Affiliation
Princess Margaret Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Margaret Cancer Center, University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin Lok, MD
Phone
416-946-4501
Ext
5819
Email
Benjamin.Lok@rmp.uhn.ca

12. IPD Sharing Statement

Plan to Share IPD
No

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Talazoparib and Thoracic RT for ES-SCLC

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