Biomarker Directed Trial of Temozolomide and Stenoparib in Relapsed SCLC (Relapsed SCLC)

March 10, 2026 updated by: VA Office of Research and Development
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

166

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304-1207
        • Recruiting
        • VA Palo Alto Health Care System, Palo Alto, CA
        • Contact:
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Not yet recruiting
        • Jesse Brown VA Medical Center, Chicago, IL
        • Contact:
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46202-2884
        • Recruiting
        • Richard L. Roudebush VA Medical Center, Indianapolis, IN
        • Principal Investigator:
          • Shadia Jalal, MD
        • Contact:
        • Contact:
    • Kentucky
      • Louisville, Kentucky, United States, 40206-1433
        • Not yet recruiting
        • Robley Rex VA Medical Center, Louisville, KY
        • Contact:
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48105-2303
        • Not yet recruiting
        • VA Ann Arbor Healthcare System, Ann Arbor, MI
        • Contact:
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417-2309
        • Not yet recruiting
        • Minneapolis VA Health Care System, Minneapolis, MN
        • Contact:
        • Contact:
    • Nebraska
      • Omaha, Nebraska, United States, 68105-1850
        • Not yet recruiting
        • Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE
        • Contact:
        • Contact:
    • North Carolina
      • Salisbury, North Carolina, United States, 28144
        • Recruiting
        • Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC
        • Contact:
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4551
        • Recruiting
        • Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
        • Contact:
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15240
        • Recruiting
        • VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
        • Contact:
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030-4211
        • Recruiting
        • Michael E. DeBakey VA Medical Center, Houston, TX
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

      • If patient is re-treated with Carboplatin and Etoposide at least 6 months or more after first regimen, this will still be considered one line of
      • treatment and they will qualify for this trial.
    • Patients could have received immunotherapy in combination with the chemotherapy regimen.
    • Patients who have received Tarlatamab as second line treatment are allowed.
  • ECOG Performance status 0-2.
  • Measurable disease as per RECIST v1.1 (NOTE: Previously irradiated lesions are eligible as a target lesion only if there is documented progression of the lesion after irradiation).

  • Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements:

    • ANC 1.5
    • Platelets 100 × 109/L
    • Hemoglobin 9 g/dL or 5.6 mmol/L
    • Aspartate transaminase and alanine transaminase 2.5 × upper limit of normal (ULN), <5× in patients with known liver metastases
    • Serum total bilirubin 1.5 × ULN, 1.5-3.0 × ULN may be included appropriate starting dose adjustment to 200 mg daily.
    • Creatinine <1.5 × ULN or estimated glomerular filtration rate (GFR) 50 ml/min by Cockcroft-Gault. Depending on scenario, GFR 30-49 can be --permissible.
  • Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test within 72 hours of cycle 1 Day 1.
  • Male and female subjects of child-bearing potential must agree to use a double-barrier method of birth control from the screening visit through 180 days after the last dose of study drug.
  • Male subjects of child-bearing potential must agree to use a double-barrier method of birth control including use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak) and must agree to refrain from donating sperm from screening visit through at least 90 days after the last dose of study drug.
  • Previously treated or asymptomatic brain metastases are allowed.

Exclusion Criteria:

  • 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.
  • Clinical significant cardiovascular disease (ie active)
  • Subject with known hypersensitivity to Stenoparib components
  • Subject with known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) are excluded.
  • Subject with QTc interval 470 for females, or 450 for males per electrocardiogram (EKG) at screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard of Care
Lurbinectedin 3.2mg/m2 one-hour intravenous (IV) infusion each cycle x21 days until disease progression or intolerable toxicity
Drug: Lurbinectedin
Lurbinectedin 3.2mg/m2 one-hour intravenous (IV) infusion x 21 days each cycle
Other Names:
  • Zepzelca
Active Comparator: Biomarker Negative Standard of Care
Lurbinectedin 3.2mg/m2 one-hour intravenous (IV) infusion each cycle x21 days until disease progression or intolerable toxicity
Drug: Lurbinectedin
Lurbinectedin 3.2mg/m2 one-hour intravenous (IV) infusion x 21 days each cycle
Other Names:
  • Zepzelca
Experimental: Study Drug Combination
Biomarker positive patients will be randomized 2:1 to study drug (Stenoparib at the recommended phase 2 dose +TMZ 40mg/day daily) or (Standard of Care) Lurbinectedin 3.2mg/m2 one-hour intravenous (IV) infusion each cycle x21 days until disease progression or intolerable toxicity
Combination product: Stenoparib/Temozolomide
Stenoparib at the recommended phase 2 dose +Temozolomide 40mg/day daily will be given in combination x21 days each cycle
Other Names:
  • Stenoparib/TEMODAR
Combination product: Stenoparib/Temozolomide
Patients 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.
Other Names:
  • Stenoparib/TEMODAR
Experimental: Safety lead-in
Biomarker positive patients 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.
Combination product: Stenoparib/Temozolomide
Stenoparib at the recommended phase 2 dose +Temozolomide 40mg/day daily will be given in combination x21 days each cycle
Other Names:
  • Stenoparib/TEMODAR
Combination product: Stenoparib/Temozolomide
Patients 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.
Other Names:
  • Stenoparib/TEMODAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: Through study completion up to 2 years.
According to response evaluation criteria in solid tumors RECIST 1.1(imaging criteria or progression or patient death).
Through study completion up to 2 years.
Recommended Phase 2 dose
Time Frame: Through end of cycle 1 (21 days)
Defined as the recommended dose of Stenoparib for phase 2
Through end of cycle 1 (21 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease control rate (DCR)
Time Frame: Through study completion up to 2 years.
Defined as Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) per RECIST 1.1.
Through study completion up to 2 years.
Overall Survival (OS)
Time Frame: Through study completion up to 2 years.
Will be measured from Day 1 of treatment until death from any cause.
Through study completion up to 2 years.
Overall response rate (ORR)
Time Frame: Through study completion up to 2 years.
Defined as complete response (CR) + partial response (PR) per RECIST 1.1 criteria.
Through study completion up to 2 years.
Treatment Toxicities
Time Frame: Through study completion up to 2 years.
As defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Through study completion up to 2 years.
Progression Free Survival (PFS)
Time Frame: Through study completion up to 2 years.
Compare PFS between biomarker positive and biomarker negative patient receiving Lurbinectedin.
Through study completion up to 2 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Principal Investigator: Shadia Jalal, MD, Richard L. Roudebush VA Medical Center, Indianapolis, IN

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2026

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

November 6, 2024

First Submitted That Met QC Criteria

November 6, 2024

First Posted (Actual)

November 8, 2024

Study Record Updates

Last Update Posted (Actual)

March 11, 2026

Last Update Submitted That Met QC Criteria

March 10, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPLP-002-24S
  • 14094144/CX002801-01A1 (Other Grant/Funding Number: VA Clinical Science Research & Development)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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