Study With Gefitinib in Combination With Olaparib (AZD2281) Versus Gefitinib Alone

NCT01513174 | Completed Phase 1 Results DMC

• 2 other identifiers: GECP10-03_GOAL2010-024178-21
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 5

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.

Conditions

Non Small Cell Lung Cancer

Keywords

GOAL; Lung; Non small cell lung cancer; EGFR mutations

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  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"

  From the date of randomization until end of follow up, up to 30 months.

Secondary Outcomes (2)

• 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

Study Arms (2)

Control Gefitinib

ACTIVE COMPARATOR

Gefitinib will be administered once daily, continuously, in 28-day cycles, as a fixed dose of 250 mg/day.

Drug: Gefitinib

Experimental: Gefitinib in combination with olaparib

EXPERIMENTAL

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.

Drug: Gefitinib; Drug: Olaparib

Interventions

Gefitinib DRUG

Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression

Also known as: Iressa

Control Gefitinib; Experimental: Gefitinib in combination with olaparib

Olaparib DRUG

Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase Ib study) twice a day, continuously, in 28-day cycles.

Also known as: Lynparza

Experimental: Gefitinib in combination with olaparib

Eligibility Criteria

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

You may qualify if:

• 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 1.1.
• ECOG score ≤ 2.
• 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
• Hemoglobin (Hb) ≥ 10 g/dl
• Platelets ≥ 100 x 109/L
• Patients with the following biochemical values:
• Bilirubin ≤ 1.5 mg/dL
• Aspartate aminotransferase (AST) and Alanine transaminase (ALT) \< 1.5 upper limit of normality

You may not qualify if:

• 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).
• Patients receiving the following classes of inhibitors of CYP3A4 (see Appendix 5 for guidelines and wash out periods):
• Azole antifungals
• Macrolide antibiotics
• Protease inhibitors
• Concomitant use of known CYP3A4 inducers such as phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort.
• Major surgery within 2 weeks of starting study treatment; patients must have recovered from any effects of any major surgery.

Sponsors & Collaborators

• Spanish Lung Cancer Group: lead

Study Sites (5)

H. Germans Trias i Pujol

Badalona, Barcelona, Spain

Location

ICO Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

H. Teresa Herrera

A Coruña, Spain

Location

H. Gen. Universitario de Alicante

Alicante, Spain

Location

H. Vall d'Hebrón

Barcelona, Spain

Location

Related Publications (1)

• Garcia-Campelo R, Arrieta O, Massuti B, Rodriguez-Abreu D, Granados ALO, Majem M, Vicente D, Lianes P, Bosch-Barrera J, Insa A, Domine M, Reguart N, Guirado M, Sala MA, Vazquez-Estevez S, Caro RB, Drozdowskyj A, Verdu A, Karachaliou N, Molina-Vila MA, Rosell R; Spanish Lung Cancer Group (SLCG). Combination of gefitinib and olaparib versus gefitinib alone in EGFR mutant non-small-cell lung cancer (NSCLC): A multicenter, randomized phase II study (GOAL). Lung Cancer. 2020 Dec;150:62-69. doi: 10.1016/j.lungcan.2020.09.018. Epub 2020 Oct 3.

  PMID: 33070053 RESULT

Related Links

• Spanish Lung Cancer Group website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib; olaparib

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Eva Pereira
• Organization: Fundación GECP

gecp@gecp.org

+34 934302006

Study Officials

• Maria Rosario García Campelo, MD

  Hospital Teresa Herrera

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: December 11, 2011
• First Posted: January 20, 2012
• Study Start: August 1, 2011
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: June 28, 2024
• Results First Posted: June 28, 2024

Record last verified: 2024-01

Locations

ES (5)