Interaction of Docetaxel and Lonafarnib in Patients With Advanced Cancer

Breast Cancer Clinical Trial

Official title:

Defining the Interaction of Docetaxel and Lonafarnib in Patients With Advanced Malignancies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00288444
• Other study ID #: 174-2004
• Secondary ID: EU841-03
• Status: Terminated
• Phase: Phase 1
• First received: February 6, 2006
• Last updated: December 17, 2012
• Start date: January 2006
• Est. completion date: March 2009

Study information

• Verified date: December 2012
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To determine the molecular interaction in tumor samples between docetaxel and lonafarnib.

Description:

1. To determine the safety and toxicity of intravenous docetaxel, administered on a weekly schedule (3 weeks out of 4), in combination with oral lonafarnib, administered on a daily schedule, in patients with locally advanced and metastatic solid tumor malignancies which are refractory to the standard of care.

2. To determine the pharmacokinetic interaction between docetaxel and lonafarnib.

3. To determine the molecular interaction in peripheral blood mononuclear cells between docetaxel and lonafarnib

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. completion date: March 2009
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:.1.1 Patient must have a pathologically-confirmed locally advanced or metastatic solid tumor malignancy demonstrated to be refractory to the standard of care, with tumors accessible by needle or surgical biopsy.

3.1.2 Only patients determined to be at minimal risk to receiving the biopsy (with tumor location/accessibility as well as underlying patient comorbidities judged to allow a minimal risk biopsy by the radiologist/surgeon performing the procedure) will be eligible for this study.

3.1.3 Patient must have an ECOG performance status of 2 or less.

3.1.4 Patient must have a life-expectancy of at least 12 weeks.

3.1.5 Patient must have adequate bone marrow function: WBC = 3,000 cells/mm3, ANC = 1,500 cells/mm3, platelet count = 100,000/mm3 and Hgb = 9.0 g/dL.

3.1.6 Patient must have adequate liver function: total bilirubin level = 2.0 mg/dL and = ULN, albumin = 2.5 g/dL.

3.1.7 Patient must have adequate renal function: Transaminases/Alkaline phosphatase: AST or ALT and alkaline phosphatase must be within the range allowing for eligibility. This range is defined as = 2 x ULN.

In determining eligibility, the more abnormal of the two (AST or ALT) should be used.

3.1.8 Patient must have received no more than three previous chemotherapy regimens (prior chemotherapy may or may not have contained a taxane).

3.1.9 Patient must meet the specified informed consent requirement.

3.1.10 Patient must be of age = 18 years.

3.1.11 Women of childbearing age must have a negative pregnancy test.

3.1.12 Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.

3.1.13 Patient must have = Grade 1 neurotoxicity from previous anticancer treatment or from any cause.

3.1.14 Patient must have adequate coagulation function: INR and PTT = 1.5 x ULN.

3.1.15 Patient must have discontinued all prior chemotherapy and radiotherapy at least 4 weeks prior to registration.

3.1.16 Patient must have discontinued use of the following drugs which are an inducers or inhibitors of CYP3A4 at least 2 days prior to registration: ethinylestradiol, gestodene, itraconazole, ketoconazole, cimetidine, erythromycin, carbamazepine, high dose chronic steroids, phenobarbital, phenytoin, rifampin (rifampcin), and sulfinpyrazone.

Patient must have a pathologically-confirmed

Exclusion Criteria:

3.2.1 Patient has received more than three previous chemotherapy regimens.

3.2.2 Patient is pregnant or breast feeding.

3.2.3 Patient has signs of symptoms of acute infection requiring systemic therapy.

3.2.4 Patient exhibits confusion, disorientation, or has a history of major psychiatric illness which may impair the patient's understanding of the informed consent.

3.2.5 Patient's life expectancy is less than 12 weeks.

3.2.6 Patient has > Grade 1 neurotoxicity from previous anticancer treatment or significant neuropathy from any cause.

3.2.7 Patient requires total parenteral nutrition with lipids.

3.2.8 Inability to swallow the lonafarnib BID.

3.2.9 Patient has a history of uncontrolled heart disease (including clinically significant coronary artery disease, congestive heart failure and symptomatic or uncontrolled arrythmias).

3.2.10 Patient has a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80. Symptoms include: any reaction such as bronchospasm, generalized urticaria, systolic BP = 80mm Hg, and angioedema.

3.2.11 Use of chronic steroids or anticonvulsants.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Colorectal Carcinoma
• Lung Cancer
• Prostate Cancer
• Sarcoma
• Soft Tissue Sarcoma

Intervention

Drug:
• Lonafarnib

• Docetaxel

Locations

Country	Name	City	State
United States	Emory University Winship Cancer Institute	Atlanta	Georgia

Sponsors (3)

Lead Sponsor	Collaborator
Emory University	Aventis Pharmaceuticals, Schering-Plough

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the molecular interaction		Four weeks	Yes
Secondary	Determine safety and efficacy		4 Weeks	Yes