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

This study has been terminated.
(This trial is being closed based on lack of substantive efficacy, slow accrual and overall tolerance in patients treated to date.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00251589
First received: November 7, 2005
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: Vorinostat
Drug: erlotinib
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: A Phase I/II Clinical Trial of Oral Vorinostat (MK0683) in Combination With Erlotinib in Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Dose Limiting Toxicity (DLT) Occurring in Cycle 1 of the Phase I Portion of the Study [ Time Frame: Day 1 to 28 in the Phase I portion of the study ] [ Designated as safety issue: Yes ]
    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.

  • Dose Limiting Toxicity Occurring in Cycle 1 of the Phase II Portion of the Study [ Time Frame: Day 1 to 28 in the Phase II portion of the study ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Unconfirmed Partial Response (UPR) Based on Response Criteria in Solid Tumors (RECIST) [ Time Frame: Every 57 days beginning with Cycle 3, or more frequently if appropriate ] [ Designated as safety issue: Yes ]
    An unconfirmed partial response is defined as a partial response that has not been confirmed by a follow up CT scan (or MRI) at least 4 weeks after the criteria for response are first met. (A partial response is defined as an at least 30% reduction in the sum of the longest diameter of the target lesions. Non-target lesions must be at least stable)

  • Stable Disease (SD) as Best Response Based on Response Criteria in Solid Tumors (RECIST) [ Time Frame: Every 57 days beginning with Cycle 3, or more frequently if appropriate ] [ Designated as safety issue: Yes ]
    Stable disease is defined as less than a radiographic partial response, but not progressive disease

  • Progressive Disease (PD) as Best Response Based on Response Criteria in Solid Tumors (RECIST) [ Time Frame: Every 57 days beginning with Cycle 3, or more frequently if appropriate ] [ Designated as safety issue: Yes ]
    Progressive disease is defined as a ≥20% increase in the sum of the longest diameter, the appearance of one or more new lesions and/or unequivocal progression of non-target lesions by conventional or spiral CT or MRI

  • Disease Progression After Week 8 Based on Response Criteria in Solid Tumors (RECIST) [ Time Frame: Every 57 days beginning with Cycle 3 (Week 8), or more frequently if appropriate ] [ Designated as safety issue: Yes ]
    First documentation of Progressive Disease (PD) occurring > 8 weeks on study.

  • Progression-free Survival [ Time Frame: Day 1 to disease progression or death ] [ Designated as safety issue: Yes ]
    Progression-free survival was measured from the start of the treatment to the time when the criteria for progression was met or death due to any cause (whichever is first recorded).


Enrollment: 23
Study Start Date: January 2006
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vorinostat 200 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
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
Vorinostat 200 mg twice a day for 3 days a week.
Other Names:
  • MK0683
  • Zolinza®
Drug: erlotinib
erlotinib 150 mg once a day.
Other Name: Tarceva ®
Experimental: Vorinostat 300 mg q.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
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
Vorinostat 300 mg once a day for 3 days a week.
Other Names:
  • MK0683
  • Zolinza®
Drug: erlotinib
erlotinib 150 mg once a day.
Other Name: Tarceva ®
Experimental: Vorinostat 300 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
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
Vorinostat 300 mg twice a day for 3 days a week.
Other Names:
  • MK0683
  • Zolinza®
Drug: erlotinib
erlotinib 150 mg once a day.
Other Name: Tarceva ®
Experimental: Vorinostat 400 mg q.d. 21d/4wk + Erlotinib 150 mg q.d. 7d/wk
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
Vorinostat 400 mg once a day for 21 out of 28 days.
Other Names:
  • MK0683
  • Zolinza®
Drug: erlotinib
erlotinib 150 mg once a day.
Other Name: Tarceva ®

  Eligibility

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

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  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: NCT00251589

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00251589     History of Changes
Other Study ID Numbers: 0683-025, MK0683-025, 2005_080
Study First Received: November 7, 2005
Results First Received: October 27, 2008
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Relapsed Non-Small-Cell Lung Cancer
Refractory Non-Small-Cell Lung Cancer

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
Erlotinib
Vorinostat
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Histone Deacetylase Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014