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

NCT00503971 | Terminated Phase 1 Results

• 2 other identifiers: TARZO2007-003646-15
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Non-small Cell Lung Cancer

Keywords

Vorinostat; NSCLC; EGFR; Erlotinib

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival Rate at 12 Weeks

  Progression Free Survival was defined as time from first treatment until progression or death from any cause.

  From date of first day of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 weeks

• Maximum Tolerated Dose (MTD) of Oral Vorinostat Phase I

  In the phase I, a classic 3 + 3 dose escalation method with 3 patients treated initially at each dose level was used. MTD was determined by testing on dose escalation cohorts: continuous full dose of erlotinib 150 mg orally (p.o.) in a daily administration(QD) and escalating doses of vorinostat p.o. at three dose levels:300 mg QD 7 days every 21 days, 400 mg QD 7 days every 21 days,and 400 mg QD, 7 days every other week. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in less than or equal to 1 in 6 patients. DLTs were defined as any Vorinostat-related Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0) Grade 3 or 4 adverse events.

  Up to 24 weeks for each dosing cohort

Secondary Outcomes (2)

• Overall Survival

  From the date of study inclusion until end of follow up, up to 36 months.

• Time to Progression

  From the date of randomization until end of follow up, up to 36 months.

Study Arms (1)

Vorinostat plus erlotinib

EXPERIMENTAL

Vorinostat plus erlotinib

Drug: Vorinostat plus Erlotinib

Interventions

Vorinostat plus Erlotinib DRUG

Phase I: Dose level 1: 300 mg V d1-7 every 21 days plus 100 mg E daily Dose level 2: 400 mg V d1-7 every 21 days plus 100 mg E daily Dose level 2b: 300 mg V d1-7 and 15-21 every 28 days plus 100 mg E daily Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily Phase II: Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily

Also known as: Zolinza® and Tarceva®

Vorinostat plus erlotinib

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed NSCLC
• Diagnosis of advanced stage IIIB with pleural effusion or IV NSCLC
• Previous disease progression after \>= 3 months treatment with Erlotinib. Must tolerate erlotinib dose of 150 mg daily during the prior month.
• 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).
• At least 18 years old.
• 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.
• At least 4 weeks from any prior major surgery or radiation therapy and have adequately recovered from the toxicities and/or complications
• ECOG performance status 0 to 2
• Adequate bone marrow function without the current use of colony stimulating factors.
• Adequate coagulation function.
• Adequate liver function
• Adequate renal function
• 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.
• Available for periodic blood sample analyses, study related assessments 15.Patient has the ability to understand and willingness to sign the informed consent form.
• Patient is able to read, understand, and complete the study questionnaires.

You may not qualify if:

• Patient has been treated with any investigational agent for any indication within 4 weeks of study treatment.
• Patient previously treated with Vorinostat or any other HDAC inhibitor for any indication in the previous 30 days.
• Patient has history of hypersensitivity or intolerance to Erlotinib.
• Patient has an active infection or has received intravenous antibiotic, antiviral or antifungal medications with 2 weeks
• Patient with symptomatic central nervous system metastases with or without corticosteroids treatment.
• Inability to take and/or tolerate oral medications.
• Patient has known active hepatitis B or C infection,(HIV) HIV-related malignancy.
• Pregnant or breastfeeding.
• Patient with a history of gastrointestinal disease, surgery
• Patient with uncontrolled undercurrent illness or circumstances that could limit compliance with the study.
• 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.
• 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.

Sponsors & Collaborators

• Spanish Lung Cancer Group: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (8)

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Instituto Universitario Dexeus

Barcelona, 08028, Spain

Location

Hospital Clinic

Barcelona, 08036, Spain

Location

Institut Catalá d'Oncologia, Centre Sanitari i Universitari de Bellvitge (CSUB)

Barcelona, 08907, Spain

Location

Institut Catalá d'Oncología, Hospital Germans Trias i Pujol

Barcelona, 08916, Spain

Location

Hospital La Paz

Madrid, 28046, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Clínico Lozano Blesa

Zaragoza, 50009, Spain

Location

Related Publications (1)

• Reguart N, Rosell R, Cardenal F, Cardona AF, Isla D, Palmero R, Moran T, Rolfo C, Pallares MC, Insa A, Carcereny E, Majem M, De Castro J, Queralt C, Molina MA, Taron M. Phase I/II trial of vorinostat (SAHA) and erlotinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression. Lung Cancer. 2014 May;84(2):161-7. doi: 10.1016/j.lungcan.2014.02.011. Epub 2014 Mar 2.

  PMID: 24636848 RESULT

Related Links

• Web page of the sponsor where users can find more information about Fundación GECP studies

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Vorinostat; Erlotinib Hydrochloride

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)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The study was stopped prematurely because it did not meet the goal required for study continuation.

Results Point of Contact

• Title: Eva Pereira
• Organization: Fundación GECP

secretaria@gecp.org

+34 934302006

Study Officials

• Teresa Moran, MD

  Medical Oncology Service. Institut Catala d'Oncologia- ICO. Hospital Germans Trias i Pujol. Badalona - Barcelona (Spain)

  PRINCIPAL INVESTIGATOR

• Dolores Isla, MD

  Medical Oncology Service. Hospital Clinico Lozano Blesa. Zaragoza. Spain

  STUDY CHAIR

• Felip Cardenal, MD

  Institut Catala d'Oncologia. Centre Sanitari i Universitari de Bellvitge (CSUB). Hospitalet de Llobregat (Barcelona). Spain

  STUDY CHAIR

• Bertomeu Massutti, MD

  Medical Oncology Service. General Hospital. Alicante. Spain

  STUDY CHAIR

• Rafael Rosell, MD

  Medical Oncology Service. Institut Catala d'Oncologia- ICO. Hospital Germans Trias i Pujol. Badalona - Barcelona (Spain)

  STUDY CHAIR

• Noemi Reguart, MD

  Medical Oncology Service. Hospital Clinic - Barcelona (Spain)

  STUDY CHAIR

• Amelia Insa, MD

  Medical Oncology Service. Hospital Clínico Universitario - Valencia (Spain)

  PRINCIPAL INVESTIGATOR

• Cinta Pallarés, MD

  Medical Oncology Service. Hospital de la Santa Creu i Sant Pau - Barcelona (Spain)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: July 18, 2007
• First Posted: July 19, 2007
• Study Start: May 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: March 7, 2025
• Results First Posted: March 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8)