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Talazoparib and Thoracic RT for ES-SCLC

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ClinicalTrials.gov Identifier: NCT04170946
Recruitment Status : Recruiting
First Posted : November 20, 2019
Last Update Posted : April 13, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University Health Network, Toronto

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.


Condition or disease Intervention/treatment Phase
Lung Cancer Small-Cell Lung Cancer Other: Talazoparib in Combination with Low Dose Radiotherapy (RT) Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation based on the maximum tolerated dose from each previous cohort within the study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Talazoparib and Consolidative Thoracic Radiotherapy for Extensive Stage Small Cell Lung Cancer
Actual Study Start Date : October 5, 2020
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Talazoparib

Arm Intervention/treatment
Experimental: Talazoparib in Combination with Low Dose RT
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.
Other: Talazoparib in Combination with Low Dose Radiotherapy (RT)
Dose escalation model to determine the safety and MTD of talazoparib in combination with low dose RT.




Primary Outcome Measures :
  1. Safety of Talazoparib in Combination with Low Dose Thoracic Radiotherapy [ Time Frame: Up to 3 years upon enrollment ]
    Safety will be measured by assessing all adverse events as determined by the investigator using CTCAE v.5.0.

  2. Maximum Tolerated Dose (MTD) of Talazoparib in Combination with Low Dose Thoracic Radiotherapy [ Time Frame: Up to 1 year ]
    MTD will be defined as the maximum dose by a standard 3+3 design


Secondary Outcome Measures :
  1. Loco-regional Recurrence [ Time Frame: 6 months and 1 year ]
    Loco-regional recurrence will be assessed by using RECIST v1.1 criteria

  2. Progression-Free Survival (PFS) [ Time Frame: 6 months and 1 year ]
    PFS will be defined as the time of start of radiotherapy to first local/loco-regional or distance recurrence event, or death.

  3. Overall Survival (OS) [ Time Frame: 6 months and 1 year ]
    OS will be defined as the time from the start of radiotherapy to death from any cause.

  4. Acute Toxicities [ Time Frame: Up to 1 year ]
    Acute toxicities will be assessed by physician-graded CTCAE.

  5. Chronic Toxicities [ Time Frame: Up to 1 year ]
    Chronic toxicities will be assessed by physician-graded CTCAE.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 or radiotherapy (except for 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04170946


Contacts
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Contact: Benjamin Lok, MD 416-946-4501 ext 5819 Benjamin.Lok@rmp.uhn.ca

Locations
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Canada, Ontario
Princess Margaret Cancer Center, University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Benjamin Lok, MD    416-946-4501 ext 5819    Benjamin.Lok@rmp.uhn.ca   
Sponsors and Collaborators
University Health Network, Toronto
Pfizer
Investigators
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Principal Investigator: Benjamin Lok, MD Princess Margaret Cancer Center
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04170946    
Other Study ID Numbers: UHN REB 19-5621
First Posted: November 20, 2019    Key Record Dates
Last Update Posted: April 13, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by University Health Network, Toronto:
Talazoparib
Thoracic Radiotherapy
Chemotherapy
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Talazoparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents