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NCT06681220 | NOT YET RECRUITING | Relapsed Small Cell Lung Cancer

Biomarker Directed Trial of Temozolomide and PARP Inhibition in Relapsed SCLC
Sponsor:

VA Office of Research and Development

Brief Summary:

Randomized phase 2, multicenter, biomarker directed clinical trial to assess the efficacy of PARP inhibitor plus Temozolomide (TMZ) in relapsed Small Cell Lung Cancer patients. This study will explore if the biomarkers the investigators test predict sensitivity to the combination of PARP inhibitor 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 PARP inhibitor 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). Participants will be assigned to one of the two groups. 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 Niraparib plus Temozolomide (TMZ) or Lurbinectedin.

Condition or disease

Relapsed Small Cell Lung Cancer

Recurrent Small Cell Lung Cancer

Intervention/treatment

PARP inhibitor/Temozolomide

Lurbinectedin

Phase

PHASE2

Detailed Description:

Randomized phase 2, multicenter, clinical trial to assess the efficacy of PARP inhibitor plus Temozolomide (TMZ) in biomarker selected relapsed SCLC patients. The investigators will test for sensitivity of two biomarkers in the blood SLFN11 and MGMT. Biomarker-positive (sensitive) patients are randomized 2:1 to either experimental Arm 2 (PARP inhibitor 200mg + 40mg TMZ oral daily for 21 days or 3.2mg/m2 Lurbinectedin IV infusion over one-hour every 21 days.). This requires 101 sensitive patients (67 on combination drug and 34 on Lurbinectedin). Biomarker-negative (resistant) patients will be enrolled on the control Arm 1 standard of care 3.2mg/m2 Lurbinectedin IV infusion over one-hour every 21 days. This requires 51 resistant patients on the control arm. The investigators will determine if biomarker (positive) sensitive patients will benefit from the oral combination PARP inhibitor + TMZ.

Study Type : INTERVENTIONAL
Estimated Enrollment : 152 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : Biomarker Directed Trial of Temozolomide and PARP Inhibition in Relapsed SCLC
Actual Study Start Date : 2025-01-01
Estimated Primary Completion Date : 2029-12-31
Estimated Study Completion Date : 2030-12-31

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
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 niraparib.
    • * Pregnant or breastfeeding.
    • * Subject with known hypersensitivity to niraparib components or excipients including tartrazine 9yellow #5) or any other study products are excluded.
    • * Subject with known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) are excluded.
    • * Participants have systolic BP \>140 mmHg or diastolic BP \>90 mmHg that has not been adequately treated or controlled.
    • * Any patient with prior history of Posterior Reversible Encephalopathy Syndrome (PRES).
Biomarker Directed Trial of Temozolomide and PARP Inhibition in Relapsed SCLC

Location Details

NCT06681220

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How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

Not yet recruiting

United States, California

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, United States, 94304-1207

Not yet recruiting

United States, California

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, United States, 90073-1003

Not yet recruiting

United States, Illinois

Jesse Brown VA Medical Center, Chicago, IL

Chicago, Illinois, United States, 60612

Not yet recruiting

United States, Indiana

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, United States, 46202-2884

Not yet recruiting

United States, Kentucky

Robley Rex VA Medical Center, Louisville, KY

Louisville, Kentucky, United States, 40206-1433

Not yet recruiting

United States, road cancer

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, road cancer, United States, 48105-2303

Not yet recruiting

United States, Minnesota

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, United States, 55417-2309

Not yet recruiting

United States, Nebraska

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

Omaha, Nebraska, United States, 68105-1850

Not yet recruiting

United States, North Carolina

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

Salisbury, North Carolina, United States, 28144

Not yet recruiting

United States, Pennsylvania

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

Philadelphia, Pennsylvania, United States, 19104-4551

Not yet recruiting

United States, Pennsylvania

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, United States, 15240