Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01513174
Recruitment Status : Completed
First Posted : January 20, 2012
Last Update Posted : April 26, 2017
Information provided by (Responsible Party):
Spanish Lung Cancer Group

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.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: Gefitinib Drug: Gefitinib plus olaparib Phase 1 Phase 2

Detailed Description:
This is a multicenter, randomized, Phase Ib/IIb, open label study to evaluate the efficacy and tolerability of 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 The study will be split into 2 parts: an open label Phase I dose escalation part and a randomized controlled, open label Phase II part.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 186 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : August 2011
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Gefitinib
Gefitinib will be administered once daily, continuously, in 28-day cycles, as a fixed dose of 250 mg/day.
Drug: Gefitinib
Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression

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.
Drug: Gefitinib plus olaparib
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.

Primary Outcome Measures :
  1. MTD (Maximum Tolerated Dose) defined as the highest dose level at which < 2 out of 6 patients experience a DLT [ Time Frame: 5 weeks ]

Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: An expected average of 2 years ]
  2. Overall response rate [ Time Frame: An expected average of 2 years ]
  3. Overall survival [ Time Frame: An expected average of 2 years ]
  4. Peak Plasma Concentration [ Time Frame: Predose, half an hour, 1, 2, 4, 6 and 12 hours post-dose ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients age 18 years or more.
  2. Histologically confirmed diagnosis of non-small-cell lung carcinoma.
  3. Stage IV disease, following the Seventh Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual (27).
  4. 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).
  5. Evidence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.
  6. ECOG score ≤ 2.
  7. Life expectancy of ≥ 3 months.
  8. 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).
  9. 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
  10. Patients with the following biochemical values:

    • Bilirubin ≤ 1.5 mg/dL
    • Aspartate aminotransferase (AST) and Alanine transaminase (ALT) < 1.5 upper limit of normality
    • Creatinine clearance ≥ 60 ml/min.
  11. Patients of childbearing age of either sex must use effective contraceptive methods(barrier methods plus other birth control methods) before entering the study and while participating in the study.
  12. Patients should sign an informed consent form before inclusion in the study that specifies that the clinical trial treatment entails consent for the analysis of biological samples of tumor and blood.
  13. Patients must be available for clinical follow-up.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. Pre-existing idiopathic pulmonary fibrosis evidenced by CT scan at baseline.
  6. Uncontrolled seizures.
  7. Patients considered requiring radiotherapy to the lung at the time of study entry or in the near future.
  8. 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.
  9. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  10. 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).
  11. Patients receiving the following classes of inhibitors of CYP3A4 (see Appendix 5 for guidelines and wash out periods):

    • Azole antifungals
    • Macrolide antibiotics
    • Protease inhibitors
  12. Concomitant use of known CYP3A4 inducers such as phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort.
  13. Major surgery within 2 weeks of starting study treatment; patients must have recovered from any effects of any major surgery.
  14. Significant weight loss (= 10% of body weight) in the 6 weeks before inclusion in the study.
  15. Any condition that is unstable or could endanger the patient's safety and/or the patient's compliance with the study.
  16. Substance abuse or clinical, psychological or social conditions that can undermine the validity of the informed consent or protocol compliance.
  17. Patients who present any contraindication or suspected allergy to the products under investigation in the study. Tablets of gefitinib contain lactose: patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose and galactose malabsorption, will not be included in this trial.
  18. Contraindication for steroid use.
  19. Impossibility to comply with treatment due to cultural or geographic circumstances.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01513174

Layout table for location information
H. Germans Trias i Pujol
Badalona, Barcelona, Spain
ICO Hospitalet
Hospitalet, Barcelona, Spain
H. Gen. Universitario de Alicante
Alicante, Spain
H. Vall d'Hebrón
Barcelona, Spain
H. Teresa Herrera
La Coruña, Spain
Sponsors and Collaborators
Spanish Lung Cancer Group
Layout table for investigator information
Study Chair: Maria Rosario García Campelo, MD Hospital Teresa Herrera
Additional Information:
Layout table for additonal information
Responsible Party: Spanish Lung Cancer Group Identifier: NCT01513174    
Other Study ID Numbers: GECP10-03
2010-024178-21 ( EudraCT Number )
First Posted: January 20, 2012    Key Record Dates
Last Update Posted: April 26, 2017
Last Verified: October 2016
Keywords provided by Spanish Lung Cancer Group:
Non small cell lung cancer
EGFR mutations
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors