NCT04170946

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.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
24

participants targeted

Target at P25-P50 for phase_1 lung-cancer

Timeline
16mo left

Started Oct 2020

Longer than P75 for phase_1 lung-cancer

Geographic Reach
1 country

1 active site

Status
recruiting

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress81%
Oct 2020Sep 2027

First Submitted

Initial submission to the registry

November 18, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 20, 2019

Completed
11 months until next milestone

Study Start

First participant enrolled

October 5, 2020

Completed
6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2027

Last Updated

March 5, 2026

Status Verified

March 1, 2026

Enrollment Period

6.9 years

First QC Date

November 18, 2019

Last Update Submit

March 3, 2026

Conditions

Small-Cell Lung CancerLung Cancer

Keywords

TalazoparibThoracic RadiotherapyChemotherapy

Outcome Measures

Primary Outcomes (2)

  • 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.

    Up to 3 years upon enrollment

  • 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

    Up to 1 year

Secondary Outcomes (5)

  • Loco-regional Recurrence

    6 months and 1 year

  • Progression-Free Survival (PFS)

    6 months and 1 year

  • Overall Survival (OS)

    6 months and 1 year

  • Acute Toxicities

    Up to 1 year

  • Chronic Toxicities

    Up to 1 year

Study Arms (1)

Talazoparib in Combination with Low Dose RT

EXPERIMENTAL

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)

Interventions

Talazoparib in Combination with Low Dose Radiotherapy (RT)OTHER

Dose escalation model to determine the safety and MTD of talazoparib in combination with low dose RT.

Talazoparib in Combination with Low Dose RT

Eligibility Criteria

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

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Princess Margaret Cancer Center, University Health Network

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

MeSH Terms

Conditions

Lung NeoplasmsSmall Cell Lung Carcinoma

Interventions

talazoparibRadiotherapy

Condition Hierarchy (Ancestors)

Respiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesCarcinoma, BronchogenicBronchial Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

  • Benjamin Lok, MD

    Princess Margaret Cancer Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin Lok, MD

CONTACT

416-946-4501Benjamin.Lok@rmp.uhn.ca

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Dose escalation based on the maximum tolerated dose from each previous cohort within the study.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 18, 2019

First Posted

November 20, 2019

Study Start

October 5, 2020

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

September 1, 2027

Last Updated

March 5, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Locations

CA(1)