A Phase I/II Clinical Trial of Vorinostat in Combination With Erlotinib for Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer (0683-025)

NCT00251589 | Terminated Phase 1 Results

• 3 other identifiers: 0683-025MK0683-0252005_080
• Study Type: interventional
• Target: 23
• Locations: 0 countries
• Sites: N/A

Brief Summary

The reason for this study will be to find the safest maximum tolerated dose of oral vorinostat in combination with erlotinib \[Tarceva (TM)\] that can be given to patients with lung cancer who have relapsed or failed other therapy for the disease. Once the safest maximum tolerated dose of vorinostat is determined, patients enrolled in the clinical trial will continue vorinostat and erlotinib for up to 8 months. Safety and effectiveness will also be evaluated.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Relapsed Non-Small-Cell Lung Cancer; Refractory Non-Small-Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT) Occurring in Cycle 1 of the Phase I Portion of the Study

  Adverse event(s) that determined the treatment dose level was not tolerable for that patient in Cycle 1 of the Phase I portion of the study.

  Day 1 to 28 in the Phase I portion of the study

• Dose Limiting Toxicity Occurring in Cycle 1 of the Phase II Portion of the Study

  Adverse event(s) that determined the treatment dose level was not tolerable for that patient in Cycle 1 of the Phase II portion of the study.

  Day 1 to 28 in the Phase II portion of the study

Secondary Outcomes (5)

• Unconfirmed Partial Response (UPR) Based on Response Criteria in Solid Tumors (RECIST)

  Every 57 days beginning with Cycle 3, or more frequently if appropriate

• Stable Disease (SD) as Best Response Based on Response Criteria in Solid Tumors (RECIST)

  Every 57 days beginning with Cycle 3, or more frequently if appropriate

• Progressive Disease (PD) as Best Response Based on Response Criteria in Solid Tumors (RECIST)

  Every 57 days beginning with Cycle 3, or more frequently if appropriate

• Disease Progression After Week 8 Based on Response Criteria in Solid Tumors (RECIST)

  Every 57 days beginning with Cycle 3 (Week 8), or more frequently if appropriate

• Progression-free Survival

  Day 1 to disease progression or death

Study Arms (4)

Vorinostat 200 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk

EXPERIMENTAL

Vorinostat 200 mg twice a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the study and determined to be the MTD and therefore the recommended Phase II dose. Of the 16 patients treated at this dose level, 4 were assigned to the Phase I portion of the study and 12 were assigned to the Phase II portion

Drug: Vorinostat; Drug: erlotinib

Vorinostat 300 mg q.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk

EXPERIMENTAL

Vorinostat 300 mg once a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the amended study and exceeded the MTD. All patients treated at this dose level were assigned to the Phase I portion of the study.

Drug: Vorinostat; Drug: erlotinib

Vorinostat 300 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk

EXPERIMENTAL

Vorinostat 300 mg twice a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the study and exceeded the MTD. All patients treated at this dose level were assigned to the Phase I portion of the study.

Drug: Vorinostat; Drug: erlotinib

Vorinostat 400 mg q.d. 21d/4wk + Erlotinib 150 mg q.d. 7d/wk

EXPERIMENTAL

Vorinostat 400 mg once a day for 21 out of 28 days + erlotinib 150 mg once a day was evaluated in the Phase I portion of the original study and exceeded MTD. This cohort was then amended (Amendment 1) to identify a more tolerable once daily vorinostat dosing regimen. All patients treated at this dose level were assigned to the Phase I portion of the study.

Drug: Vorinostat; Drug: erlotinib

Interventions

Vorinostat DRUG

Vorinostat 200 mg twice a day for 3 days a week.

Also known as: MK0683, Zolinza®

Vorinostat 200 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk

erlotinib DRUG

erlotinib 150 mg once a day.

Also known as: Tarceva ®

Vorinostat 200 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk; Vorinostat 300 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk; Vorinostat 300 mg q.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk; Vorinostat 400 mg q.d. 21d/4wk + Erlotinib 150 mg q.d. 7d/wk

Eligibility Criteria

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

You may qualify if:

• Males and females 18 years of age and older with a confirmed diagnosis of non-small-cell lung cancer (NSCLC) who have failed at least one prior treatment for NSCLC.
• Patients must have proven disease by CT scan or MRI.
• Patients must be at least 4 weeks from any chemotherapy for cancer or from any surgeries or from any treatment using an investigational drug.
• Patients must be 2 weeks out from radiation therapy.
• At screening the patient must have normal lab results and can not be pregnant.
• Women and men must agree to practice adequate birth control during the study.
• Patient has the ability to understand and sign the consent form.

You may not qualify if:

• Patient had prior treatment with vorinostat or erlotinib.
• Patient has any of the following conditions: active infections including hepatitis B or C, unstable brain metastases, swallowing difficulties, heart problems, significant eye abnormalities, drug or alcohol abuse, mental illness or pregnancy.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

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

Due to the slow pace of patient accrual, failure to observe meaningful efficacy in treated patients, and overall intolerance of the combination regimen, the study was terminated prematurely on 12-Oct-2007.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 7, 2005
• First Posted: November 10, 2005
• Study Start: January 1, 2006
• Primary Completion: October 1, 2007
• Study Completion: October 1, 2007
• Last Updated: March 6, 2015
• Results First Posted: March 10, 2009

Record last verified: 2015-02