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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Spanish Lung Cancer Group
Sponsor:
Information provided by (Responsible Party):
Spanish Lung Cancer Group
ClinicalTrials.gov Identifier:
NCT01513174
First received: December 11, 2011
Last updated: March 8, 2013
Last verified: March 2013
  Purpose

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 Intervention Phase
Non Small Cell Lung Cancer
Drug: Gefitinib
Drug: Gefitinib plus olaparib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Spanish Lung Cancer Group:

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

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: An expected average of 2 years ] [ Designated as safety issue: No ]
  • Overall response rate [ Time Frame: An expected average of 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: An expected average of 2 years ] [ Designated as safety issue: No ]
  • Peak Plasma Concentration [ Time Frame: Predose, half an hour, 1, 2, 4, 6 and 12 hours post-dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 186
Study Start Date: August 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01513174

Contacts
Contact: SLCG 34 93 430 20 06 secretaria@gecp.org

Locations
Spain
H. Germans Trias i Pujol Recruiting
Badalona, Barcelona, Spain
Contact: Rafael Rosell, MD         
Principal Investigator: Rafael Rosell, MD         
ICO Hospitalet Recruiting
Hospitalet, Barcelona, Spain
Contact: Felipe Cardenal, MD         
Principal Investigator: Felipe Cardenal, MD         
H. Gen. Universitario de Alicante Recruiting
Alicante, Spain
Contact: Bartomeu Massutí, MD         
Principal Investigator: Bartomeu Massutí, MD         
H. Vall d'Hebrón Recruiting
Barcelona, Spain
Contact: Enriqueta Felip, MD         
Principal Investigator: Enriqueta Felip, MD         
H. Teresa Herrera Recruiting
La Coruña, Spain
Contact: Charo García Campelo, MD         
Principal Investigator: Maria Rosario García Campelo, MD         
Sponsors and Collaborators
Spanish Lung Cancer Group
Investigators
Study Chair: Maria Rosario García Campelo, MD Hospital Teresa Herrera
  More Information

Additional Information:
No publications provided

Responsible Party: Spanish Lung Cancer Group
ClinicalTrials.gov Identifier: NCT01513174     History of Changes
Other Study ID Numbers: GECP10-03, 2010-024178-21
Study First Received: December 11, 2011
Last Updated: March 8, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Spanish Lung Cancer Group:
GOAL
Lung
Non small cell lung cancer
EGFR mutations

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gefitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014