Multicenter, Randomized, Phase Ib/IIb Study to Evaluate the Efficacy and Tolerability of Gefitinib in Combination With Olaparib (AZD2281) Versus Gefitinib Alone, in Patients With EGFR Mutation Positive Advanced Non-small-cell Lung Cancer
Overview
- Phase
- Phase 1
- Intervention
- Gefitinib
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Spanish Lung Cancer Group
- Enrollment
- 186
- Locations
- 5
- Primary Endpoint
- Progression-free Survival (PFS)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a study of gefitinib plus olaparib gefitinib in combination with olaparib (AZD2281) versus gefitinib alone, in patients with Epidermal Growth Factor Receptor (EGFR) mutation positive advanced non-small-cell lung cancer.
Detailed Description
GOAL is a multicenter, randomized phase IB/II study performed in two countries, Spain and Mexico. Eligible patients were 18 years or older, treatment-naïve, pathologically confirmed stage IV NSCLC, with centrally confirmed EGFR mutations and measurable disease. Patients were randomly allocated (1:1) to receive gefitinib 250 mg daily or gefitinib 250 mg daily plus olaparib 200 mg three times daily in 28-day cycles. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), response rate, safety and tolerability.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients age 18 years or more.
- •Histologically confirmed diagnosis of non-small-cell lung carcinoma.
- •Stage IV disease, following the Seventh Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual (27).
- •Tumor tissue available (according to the criterion of the specimen-processing laboratory) for EGFR mutation assessment: to be included in the study patients should present at least one EGFR mutation (exon 19 deletion or L858R with or without T790M).
- •Evidence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.
- •ECOG score ≤
- •Life expectancy of ≥ 3 months.
- •For the Phase II part of the study, patients should not have received previous treatment with chemotherapy or other agents for advanced disease: chemotherapy is allowed if the initial diagnosis of the patient is limited disease and the patient has received adjuvant or neoadjuvant treatment, as long as a minimum of 6 months has passed since the end of the adjuvant and/or neo-adjuvant chemotherapy. This criterion is not mandatory to patients to be included in the Phase I part of the study (these patients are allowed to have received a prior line of treatment for advanced disease).
- •Patients with the following hematologic values:
- •Absolute Neutrophil Count (ANC) ≥1.5 x 109/L
Exclusion Criteria
- •Patients diagnosed of another neoplasm, with the exception of cervical carcinoma insitu, treated squamous cell carcinoma or superficial bladder tumor (Ta and TIS), or other malignant tumors that have received curative treatment within the last 5 years before inclusion in the study.
- •Simultaneous participation in any other study involving an investigational medicinal product, or having participated in a study less than 28 days prior to the start of study treatment.
- •Patients with HIV infection, HCV infection, coronary disease or uncontrolled arrhythmia, uncontrolled cerebrovascular disease and other clinical conditions that, in the judgment of the investigator, contraindicate the patient's participation in the study.
- •Past medical history of interstitial lung disease (ILD), drug-induced interstitial disease, radiation pneumonitis which required steroid treatment or any evidence of clinically active interstitial lung disease.
- •Pre-existing idiopathic pulmonary fibrosis evidenced by CT scan at baseline.
- •Uncontrolled seizures.
- •Patients considered requiring radiotherapy to the lung at the time of study entry or in the near future.
- •Known or suspected brain metastases or spinal cord compression, unless treated with surgery and/or radiation and stable without steroid treatment for at least 4 weeks prior to the first dose of study medication.
- •Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
- •Patients who are pregnant or breastfeeding. Women of childbearing potential must have a negative pregnancy test performed within 7 days before the onset of treatment(Appendix 8).
Arms & Interventions
Control Gefitinib
Gefitinib will be administered once daily, continuously, in 28-day cycles, as a fixed dose of 250 mg/day.
Intervention: Gefitinib
Experimental: Gefitinib in combination with olaparib
Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase I study) twice a day, continuously, in 28-day cycles.
Intervention: Gefitinib
Experimental: Gefitinib in combination with olaparib
Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase I study) twice a day, continuously, in 28-day cycles.
Intervention: Olaparib
Outcomes
Primary Outcomes
Progression-free Survival (PFS)
Time Frame: From the date of randomization until end of follow up, up to 30 months.
Defined as the length of time from the date of randomization to the date of the first documented progression of disease. "Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions"
Secondary Outcomes
- Overall Survival(From the date of randomization until end of follow up, up to 30 months)
- Best Global Response During Treatment Period(From the date of randomization until end of follow up, up to 30 months)