Randomized Phase 3 Trial of Gemcitabine/Carboplatin With or Without Iniparib (SAR240550) (a PARP1 Inhibitor) in Subjects with Previously Untreated Stage IV Squamous Non-Small-Cell Lung Cancer (NSCLC)

Study Objective

Primary

To evaluate the overall survival of patients with stage IV squamous NSCLC receiving gemcitabine /carboplatin either with or without iniparib.

Secondary

The secondary objectives of this study are to evaluate the following in patients with stage IV squamous NSCLC receiving gemcitabine/carboplatin either with or without iniparib:

• Progression free survival (PFS)
• Time to progression (TTP)
• Objective response rate (ORR)
• Safety and tolerability of the treatment regimen
• Quality of life as measured by EORTC QLQ-30 and QLQ-LC13

Participation conditions

This is a randomized, Phase 3, open label, two-arm study in patients with stage IV squamous NSCLC. Patients will be randomized in a 1:1 ratio into one of two treatment arms:

• Arm A: gemcitabine/carboplatin + iniparib
• Arm B: gemcitabine/carboplatin

Inclusion criteria
 

• Newly diagnosed, stage IV squamous NSCLC. This includes patients who present with disseminated metastases, and those with a malignant pleural or pericardial effusion (i.e., formerly stage IIIB in the 6th TNM staging system).
• Patients who have received prior adjuvant therapy for early-stage lung cancer are eligible if at least 12 months have elapsed from that treatment.
• Histologically confirmed squamous cell bronchogenic carcinoma. Patients whose tumors contain mixed non-small cell histologies are eligible, as long as squamous carcinoma is the predominant histology. Mixed tumors with small cell anaplastic elements are not eligible. Cytologic specimens obtained by brushings, washings, or needle aspiration of the defined lesion are acceptable.
• Patients with previous radiotherapy as definitive therapy for locally advanced non-small cell lung cancer are eligible, as long as the recurrence is outside the original radiation therapy port. Radiation therapy must have been completed >4 weeks prior to the date the Informed Consent is signed.
• Presence of evaluable (measureable or non-measurable) disease.
• ECOG Performance Status of 0 or 1.
• Laboratory values as follows:
  • Absolute neutrophil count (ANC) ≥1,500/μL and platelet count ≥100,000/μL
  • Hemoglobin >9 g/dL
  • Bilirubin < ULN.
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal if no liver involvement or ≤5 times the upper limit of normal with liver involvement.
  • Creatinine ≤2.0 mg/dL, or creatinine clearance ≥40 mL/min.
     
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment, and at least 3 months after the last dose of study treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
• ≥18 years of age.
• Ability to understand the nature of this study, give written informed consent, and comply with study requirements.
• Patients entering this study must be willing to provide tissue from a previous tumor biopsy (if available) for correlative testing. If tissue is not available, a patient will still be eligible for enrollment into the study.

Exclusion criteria

• Prior treatment with gemcitabine, carboplatin (except in the adjuvant setting), or iniparib.
• Past or current history of neoplasm other than the entry diagnosis, with the exception of treated non-melanoma skin cancer or carcinoma in-situ of the cervix, or other cancers cured by local therapy alone and a disease-free survival of ≥5 years.
• A history of cardiac disease, as defined by:
  • Malignant hypertension
  • nstable angina
  • Congestive heart failure
  • Myocardial infarction within the previous 6 months
  • Symptomatic cardiac arrhythmias
     
• Active brain metastases. Patients with treated brain metastases are eligible, if (1) radiation therapy was completed at least 2 weeks prior to study entry; (2) follow-up scan shows no disease progression; and (3) patient does not require steroids.
• Women who are pregnant or lactating.
• Any serious, active infection (> Grade 2) at the time of treatment.
• A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
• A major surgical procedure, open biopsy, or significant traumatic injury ≤28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study.
• Uncontrolled or intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• History of any medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with the study participation or administration of the investigational products, or that may interfere with the interpretation of the results.
• Known or suspected allergy/hypersensitivity to any agent given in the course of this trial.
• Use of any non-approved or investigational agent ≤30 days prior to administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.

Centre Hospitalier de Luxembourg