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

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Vorinostat; Drug: erlotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT00251589

0683-025

2005_080 (Other Identifier)

MK0683-025 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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23 participants in 4 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: erlotinib

Drug: Vorinostat

Drug: Vorinostat

Drug: Vorinostat

Drug: Vorinostat

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

Experimental group

Description:

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.

Treatment:

Drug: erlotinib

Drug: Vorinostat

Drug: Vorinostat

Drug: Vorinostat

Drug: Vorinostat

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

Experimental group

Description:

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.

Treatment:

Drug: erlotinib

Drug: Vorinostat

Drug: Vorinostat

Drug: Vorinostat

Drug: Vorinostat

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

Experimental group

Description:

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.

Treatment:

Drug: erlotinib

Drug: Vorinostat

Drug: Vorinostat

Drug: Vorinostat

Drug: Vorinostat