Phase I/II of Oral Vorinostat Combination With Erlotinib in NSCLC Patients With EGFR Mutations With DP After Erlotinib.

• Status: Terminated
• Trial end date: 2011-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an open label, non-randomized, sequential, phase I/II trial in patients with stage IIIB or IV non-small cell lung cancer (NSCLC) with EGFR mutations after progression to Erlotinib. The study will have two parts. The first part (phase I) will be a dose finding (MTD) study to be implemented at three hospitals. The second part of the study (phase II) will asses the safety and efficacy of the combination. In this second part (phase II) patients will be treated with oral Erlotinib 150 mg P.O daily plus oral Vorinostat administered according to the results of the phase I. The study endpoints to be evaluated will include safety and response rate (RR) as primary endpoints and clinical benefit rate (CBR), time to progression, time to response, response duration and progression free survival as secondary endpoints. All the patients (phase I and II) will be treated until progression disease, unacceptable toxicity or withdrawal of the consent, and will be treated at the discretion of the principal investigator.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Spanish Lung Cancer Group
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Erlotinib Hydrochloride; Vorinostat

Criteria

Inclusion Criteria:

1. Histologically confirmed NSCLC

2. Diagnosis of advanced stage IIIB with pleural effusion or IV NSCLC

3. Previous disease progression after >= 3 months treatment with Erlotinib. Must tolerate erlotinib dose of 150 mg daily during the prior month.

4. Have demonstrated mutations at epidermal growth factor receptor (EGFR) at Exon 19 or Exon 21 (Exon 19 mutations characterized by in-frame deletions (747-750), and Exon 21 mutations resulting in L858R substitutions).

5. At least 18 years old.

6. Measurable disease as defined by the presence of at least one lesion that can be accurately measured in at least one dimension using RECIST guidelines.

7. At least 4 weeks from any prior major surgery or radiation therapy and have adequately recovered from the toxicities and/or complications

8. ECOG performance status 0 to 2

9. Adequate bone marrow function without the current use of colony stimulating factors.

10. Adequate coagulation function.

11. Adequate liver function

12. Adequate renal function

13. Non-sterilized premenopausal female, pregnancy test must be performed and patient must agree to use barrier methods of contraception. Male patients must agree to use an adequate method of contraception.

14. Available for periodic blood sample analyses, study related assessments 15.Patient has the ability to understand and willingness to sign the informed consent form.

16.Patient is able to read, understand, and complete the study questionnaires.

Exclusion Criteria:

1. Patient has been treated with any investigational agent for any indication within 4 weeks of study treatment.

2. Patient previously treated with Vorinostat or any other HDAC inhibitor for any indication in the previous 30 days.

3. Patient has history of hypersensitivity or intolerance to Erlotinib.

4. Patient has an active infection or has received intravenous antibiotic, antiviral or antifungal medications with 2 weeks

5. Patient with symptomatic central nervous system metastases with or without corticosteroids treatment.

6. Inability to take and/or tolerate oral medications.

7. Patient has known active hepatitis B or C infection,(HIV) HIV-related malignancy.

8. Pregnant or breastfeeding.

9. Patient with a history of gastrointestinal disease, surgery

10. Patient with uncontrolled undercurrent illness or circumstances that could limit compliance with the study.

11. History of malignancy except for inactive non-melanoma skin cancer and/or in situ carcinoma of the cervix, or other solid tumor treated curatively and without evidence of recurrence for at least 5 years prior to study enrollment.

12. Patient has had prescription or non-prescription drugs or other products known to influence CYP3A4 that cannot be discontinued prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication.