Biomarker Directed Trial of Temozolomide and Stenoparib in Relapsed SCLC
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorVA Office of Research and Development
About this trial
Randomized phase 2, multicenter, biomarker directed clinical trial with a safety lead-in to assess the efficacy of Stenoparib plus Temozolomide (TMZ) in relapsed Small Cell Lung Cancer patients. Participants will receive either a combination of oral Stenoparib at the highest tolerated dose with oral Temozolomide 40mg daily or standard of care Lurbinectedin for 21-day cycles. The Dose limiting toxicity period will be 1 cycle of 21 days. This study will explore if the biomarkers the investigators test predict sensitivity to the combination of Stenoparib plus TMZ and therefore leads to a better treatment response. There are two potential tests of biomarkers that can predict who would benefit from the oral combination of Stenoparib with Temozolomide (TMZ), but they have not been evaluated. This study will test for this sensitivity using a biomarker (found in the blood that may be related to how a person reacts to a drug). The study will include 9 participants for the safety evaluation of the Stenoparib+TMZ group and 5 participants for the standard of care Lurbinectedin safety group. We will first determine safety dose for the experiment arm which, will include 3 groups with 3 participants in each group. Three doses of Stenoparib will be evaluated for toxicity. The initial starting dose of Stenoparib will be 200mg po QD. Once the maximum tolerated dose has been determined, participants will be assigned to one of the two groups in the phase 2 portion. Group 1 will be patients that test negative for the biomarker and will receive treatment with Lurbinectedin as per standard of care guidelines. Group 2 will be patients that test positive for the biomarker that will be randomly assigned to either the combination of Stenoparib plus Temozolomide (TMZ) or Lurbinectedin.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age 18 years or older at the time of consent.
Histological or cytological diagnosis of extensive-stage small cell lung cancer.
Patients must have received one prior line of systemic therapy.
Patients must have received first-line therapy with Carboplatin and Etoposide.
Disqualifiers
Unstable or clinically significant concurrent medical condition, psychiatric illness or social situation that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol.
Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy. (Suppressive therapy for chronic infections allowed, for example: Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed. Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy.)
Prior exposure to lurbinectedin, TMZ or stenoparib.
Pregnant or breastfeeding.
Trial design
Design model
Sequential
Treatments tested in this trial
Stenoparib/Temozolomide
Combination productStenoparib at the recommended phase 2 dose +Temozolomide 40mg/day daily will be given in combination x21 days each cycle
Lurbinectedin
DrugLurbinectedin 3.2mg/m2 one-hour intravenous (IV) infusion x 21 days each cycle
Stenoparib/Temozolomide
Combination productPatients will be assigned to one of three doses of Stenoparib (200mg po qd, 200mg po BID, and 200mg in am and 400mg in pm). The initial starting dose will be the 200 mg po QD orally daily for 21 days.
Treatment groups
166 Participants
are divided into 4 treatment groupsGroup A: Study Drug CombinationExperimental treatment 1 intervention
Group B: Standard of CareActive comparator 1 intervention
Group C: Biomarker Negative Standard of CareActive comparator 1 intervention
Group D: Safety lead-inExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Progression Free Survival (PFS)
According to response evaluation criteria in solid tumors RECIST 1.1(imaging criteria or progression or patient death).
Time frame
Through study completion up to 2 years.2
Recommended Phase 2 dose
Defined as the recommended dose of Stenoparib for phase 2
Time frame
Through end of cycle 1 (21 days)Secondary outcomes
1
Disease control rate (DCR)
Defined as Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) per RECIST 1.1.
Time frame
Through study completion up to 2 years.2
Overall Survival (OS)
Will be measured from Day 1 of treatment until death from any cause.
Time frame
Through study completion up to 2 years.3
Overall response rate (ORR)
Defined as complete response (CR) + partial response (PR) per RECIST 1.1 criteria.
Time frame
Through study completion up to 2 years.4
Treatment Toxicities
As defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Time frame
Through study completion up to 2 years.Sponsors and contacts
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Source ClinicalTrials.gov