A Study to Evaluate the Safety, Tolerability, and Activity of Lonafarnib and Docetaxel (Study P04467AM1)(TERMINATED)

An Open-Label, Two-Part Study to Determine the Safety, Tolerability, and Activity of Lonafarnib and Docetaxel

This study will determine the best doses of docetaxel and lonafarnib when the two anti-cancer agents are used in combination. Patients with tumors for which treatment with docetaxel would be appropriate are eligible. A second part of the study will further examine the effectiveness of the combination treatment in men with prostate cancer.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Gastric Cancer; Ovarian Cancer; Lung Cancer; Prostate Cancer
• Intervention / Treatment: Drug: Docetaxel plus lonafarnib

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For Part 1: Subjects may be male or female and must be at least 18 years of age.
• For Part 1: Cancer for which docetaxel treatment is appropriate.
• For Part 1: Docetaxel-naïve
• For Part 2: Subjects must be male and at least 18 years of age.
• For Part 2: Subjects must have adenocarcinoma of the prostate confirmed by histologic/cytologic biopsy.
• For Part 2: Subjects must have progressive, metastatic, AIPC and a PSA of 10 ng/ml or more after hormonal therapy prior to docetaxel treatment. Progressive disease is defined as a consistently increasing serum PSA level within 28 days prior to docetaxel administration.
• Adequate organ function within 3 weeks prior to first study drug administration.
• Performance status (ECOG) is less than or equal to 2.
• Subject understands and agrees to procedures and participation by signing informed consent form.
• Agrees to use medically accepted form of contraception.

Exclusion Criteria:

• Receipt of or need to continue to receive prohibited medications (listed in the protocol) more recently than the washout period (indicated in the protocol).
• Surgery within 3 weeks prior to first study drug administration.
• History within 5 years prior to first study drug administration of another malignancy except adequately treated Stage I/II basal/squamous cell skin cancer.
• Radiation therapy to more than 25% of his/her total bone marrow during life.
• Radiation therapy within 3 weeks prior to first study drug administration.
• Known hypersensitivity to prednisone, docetaxel, polysorbate 80, lonafarnib, or any excipients associated with these medications.
• Known contraindication to steroid use.
• Known leptomeningeal or CNS metastasis.
• Heart, vascular, or seizure disorder (detailed list in the protocol) within 6 months prior to first study drug administration.
• Baseline QTc interval greater than 450 msec.
• Grade 2 or more peripheral neuropathy or drug-related toxicity per CTCAE. Exceptions are noted in the protocol.
• Any clinically significant condition or situation that the investigator thinks would interfere with the study evaluations or subject's participation.
• Subject is part of staff personnel involved in the study.
• Subject has known clinically significant immunosuppression.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Docetaxel plus lonafarnib (single arm); Docetaxel plus lonafarnib	Drug: Docetaxel plus lonafarnib; Docetaxel: 60-75 mg/m2 Lonafarnib: 150-375 mg PO BID; Other Names: Docetaxel (Taxotere®); lonafarnib (SCH 066336, Sarasar®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events and dose-limiting toxicities	Until disease progression, unacceptable dose delays or reductions, or unacceptable toxicity
Rate of prostate-specific antigen (PSA) responses	Until disease progression, unacceptable dose delays or reductions, or unacceptable toxicity

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with dose-limiting toxicities	Until disease progression, unacceptable dose delays or reductions, or unacceptable toxicity
Plasma lonafarnib concentrations	Until disease progression, unacceptable dose delays or reductions, or unacceptable toxicity
RECIST-defined radiological response rate	Until disease progression, unacceptable dose delays or reductions, or unacceptable toxicity

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: October 4, 2007
• First Submitted That Met QC Criteria: October 4, 2007
• First Posted (Estimate): October 5, 2007

Study Record Updates

• Last Update Posted (Estimate): February 5, 2015
• Last Update Submitted That Met QC Criteria: February 4, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Lonafarnib
• Other Study ID Numbers: P04467