Combining talazoparib and low-dose temozolomide for advanced small cell lung cancer

A Phase 2 Study of Continuous Talazoparib Plus Intermittent Low-Dose Temozolomide in Patients With Relapsed or Refractory Extensive-Stage Small Cell Lung Cancer (TRIO-US L-07)

This study is testing if combining two drugs, talazoparib and low-dose temozolomide, can help people with advanced small cell lung cancer that hasn't responded to other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jonsson Comprehensive Cancer Center (Academic / other)
• Drugs / interventions: rovalpituzumab, chemotherapy, immunotherapy, radiation
• Locations: 6 sites (Bakersfield, California and 5 other locations)
• Trial ID: NCT03672773 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of talazoparib, a PARP inhibitor, in combination with temozolomide for treating patients with relapsed or refractory extensive-stage small cell lung cancer. The study aims to evaluate the objective response rate, progression-free survival, overall survival, and safety of this combination therapy. Participants will receive temozolomide orally for five days and talazoparib daily for 28 days, with treatment cycles repeating every 28 days if there is no disease progression or unacceptable toxicity. The trial also includes exploratory objectives to identify potential biomarkers associated with treatment response.

Who should consider this trial

Good fit: Ideal candidates include individuals with extensive-stage small cell lung cancer that has relapsed or is refractory after initial chemotherapy.

Not a fit: Patients with early-stage small cell lung cancer or those who have not received prior chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with advanced small cell lung cancer who have limited options.

How similar studies have performed: Other studies have shown promise with PARP inhibitors in combination with chemotherapy, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Able to provide informed consent.
* Cytologically or histologically confirmed small cell lung cancer (SCLC) with extensive-stage disease.
* Relapsed (progressed within 6 months) or refractory (progressed during or within 4 weeks of completing 1st line platinum based regimen).
* Measurable disease, as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
* Archival or fresh tissue biopsy available for exploratory analyses.
* Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1.
* Able to swallow the study drugs, has no known intolerance to study drugs or excipients, and able to comply with study requirements.
* Female participants of childbearing potential must have a negative pregnancy test at screening and must agree to use a highly effective birth control method (defined in protocol) from the time of the first study drug treatment through 45 days after the last study drug treatment.
* Male participants must use a condom when having sex from the time of the first study drug treatment through 105 days after the last study drug treatment. Contraception should be considered for a non-pregnant female partner of childbearing potential.
* Male and female participants must agree not to donate sperm or eggs, respectively, from the first study drug treatment through 105 days and 45 days after the last study drug treatment, respectively.
* Female participants may not be breastfeeding at baseline through 45 days after the last study drug treatment.
* Absolute neutrophil count (ANC) \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
* Glomerular filtration rate (by Cockroft-Gault or equivalent estimation) \>= 30 mL/min
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for participants with liver metastases
* Serum total bilirubin =\< 1.5 X upper limit or normal (ULN) OR direct bilirubin =\< ULN for participants with total bilirubin levels \> 1.5 ULN
* International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless participant is receiving anticoagulant therapy, as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
* Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless participant is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria:

* Has not recovered (recovery is defined as Common Terminology Criteria for Adverse Events (CTCAE) version (v)4 grade =\< 1 or return to baseline) from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
* Best response of progressive disease per RECIST 1.1 to first-line platinum doublet chemotherapy.
* Has received more than 1 line of cytotoxic therapy

  * Prior immunotherapy and targeted therapies (including rovalpituzumab tesirine) are allowed.
* Prior treatment with a PARP inhibitor (not including iniparib) or temozolomide.
* Use of antineoplastic therapies within 14 days before study treatment initiation.
* Use of any other investigational agent within 14 days before study treatment initiation.
* Received radiation therapy within 14 day before study treatment initiation (single fraction palliative radiotherapy is allowed without a washout).

  * Prior thoracic irradiation and prophylactic cranial irradiation are allowed.
* Major surgery within 14 days before study treatment initiation.
* Diagnosis of myelodysplastic syndrome (MDS).
* Gastrointestinal disorder affecting absorption.
* Current or anticipated use of a prohibited P-gp inhibitor or P-gp inducer or BCRP inhibitors.
* History of another cancer within 2 years before study treatment initiation, with the exception of fully treated cancers unlikely to affect the assessment of the study treatment safety or efficacy including early stage breast, prostate, nonmelanomatous skin, thyroid, cervix and endometrial cancer.
* Any condition (concurrent disease, infection, or comorbidity) that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of safety data, in the opinion of the investigator.

Where this trial is running

Bakersfield, California and 5 other locations

• CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center — Bakersfield, California, United States (Recruiting)
• St. Joseph Heritage Healthcare — Fullerton, California, United States (Recruiting)
• UCLA / Jonsson Comprehensive Cancer Center — Los Angeles, California, United States (Recruiting)
• Orlando Health, Inc. d/b/a Orlando Health UF Health Center — Orlando, Florida, United States (Recruiting)
• Ft. Wayne Medical Oncology and Hematology, Inc. — Fort Wayne, Indiana, United States (Recruiting)
• Cancer Center of Kansas — Wichita, Kansas, United States (Recruiting)

Study contacts

• Principal investigator: Jonathan Goldman, MD — UCLA / Jonsson Comprehensive Cancer Center
• Study coordinator: TRIO-US IST Team

Conditions Recurrent Extensive Stage Small Cell Lung Carcinoma; Refractory Extensive Stage Small Cell Lung Carcinoma; Small Cell Lung Cancer; PARP Inhibitor