Biomarker Directed Trial of Temozolomide and Stenoparib in Relapsed SCLC

NCT06681220 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: SPLP-002-24S14094144/CX002801-01A1
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Recurrent Small Cell Lung Cancer; Relapsed Small Cell Lung Cancer

Keywords

Phase 2; Small Cell Lung Cancer; Biomarker

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS)

  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

  Defined as the recommended dose of Stenoparib for phase 2

  Through end of cycle 1 (21 days)

Secondary Outcomes (5)

• Disease control rate (DCR)

  Through study completion up to 2 years.

• Overall Survival (OS)

  Through study completion up to 2 years.

• Overall response rate (ORR)

  Through study completion up to 2 years.

• Treatment Toxicities

  Through study completion up to 2 years.

• Progression Free Survival (PFS)

  Through study completion up to 2 years.

Study Arms (4)

Study Drug Combination

EXPERIMENTAL

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

Standard of Care

ACTIVE COMPARATOR

Lurbinectedin 3.2mg/m2 one-hour intravenous (IV) infusion each cycle x21 days until disease progression or intolerable toxicity

Drug: Lurbinectedin

Biomarker Negative Standard of Care

ACTIVE COMPARATOR

Lurbinectedin 3.2mg/m2 one-hour intravenous (IV) infusion each cycle x21 days until disease progression or intolerable toxicity

Drug: Lurbinectedin

Safety lead-in

EXPERIMENTAL

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

Interventions

Lurbinectedin DRUG

Lurbinectedin 3.2mg/m2 one-hour intravenous (IV) infusion x 21 days each cycle

Also known as: Zepzelca

Biomarker Negative Standard of Care; Standard of Care

Stenoparib/Temozolomide COMBINATION_PRODUCT

Stenoparib at the recommended phase 2 dose +Temozolomide 40mg/day daily will be given in combination x21 days each cycle

Also known as: Stenoparib/TEMODAR

Study Drug Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (11)

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, 94304-1207, United States

RECRUITING

Jesse Brown VA Medical Center, Chicago, IL

Chicago, Illinois, 60612, United States

NOT YET RECRUITING

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, 46202-2884, United States

RECRUITING

Robley Rex VA Medical Center, Louisville, KY

Louisville, Kentucky, 40206-1433, United States

NOT YET RECRUITING

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105-2303, United States

NOT YET RECRUITING

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417-2309, United States

NOT YET RECRUITING

Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE

Omaha, Nebraska, 68105-1850, United States

NOT YET RECRUITING

Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC

Salisbury, North Carolina, 28144, United States

RECRUITING

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Philadelphia, Pennsylvania, 19104-4551, United States

RECRUITING

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, 15240, United States

RECRUITING

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030-4211, United States

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

stenoparib; Temozolomide; PM 01183

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Shadia Jalal, MD

  Richard L. Roudebush VA Medical Center, Indianapolis, IN

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shadia Jalal, MD

CONTACT

(317) 274-5500; Shadia.Jalal@va.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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. Participants will receive either a combination of oral Stenoparib at the highest tolerated dose with oral Temozolomide 40mg daily or standard of care Lurbinectin for 21-day cycles.

Study Record Dates

• First Submitted: November 6, 2024
• First Posted: November 8, 2024
• Study Start: February 23, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)