Clinical trial NCT00050141: Study of Letrozole Plus Tipifarnib or Placebo in the Treatment of Advanced Breast Cancer
Official title: A Randomised, Blinded, Phase 2 Study of Letrozole Plus the Farnesyl Transferase Inhibitor ZARNESTRA TM (R115777) and Letrozole Plus Placebo in the Treatment of Advanced Breast Cancer After Antiestrogen Therapy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast cancer
ZARNESTRA
tipifarnib
R115777
Estrogen receptor positive
Progesterone receptor positive
Anti-estrogen therapy
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2002-11-28
Enrollment: 121
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if the addition of tipifarnib to standard letrozole therapy leads to a better response to treatment for your cancer in comparison to letrozole plus a placebo. Tipifarnib belongs to a class of drugs called Farnesyl Transferase Inhibitors (FTI). It blocks proteins that make cancer cells grow.

Detailed description: This clinical study involves two groups of patients with advanced breast cancer. One group (2/3rds of all the patients) will be taking tipifarnib in combination with another anticancer drug called letrozole, and the other group (1/3rd of all the patients) will be taking letrozole plus a placebo (an inactive substance given in the same form as a real drug). The assignment to one of these two groups will be by chance (like flipping a coin). Unless the need arises, neither the patient nor the study staff will know whether the patient is receiving tipifarnib with the letrozole. Comparisons between the two groups will be made for patients who have achieve a confirmed Complete Response (CR) or Partial Response (PR). The interval between the date of randomization and the earliest date of disease progression will also be assessed. The study will include evaluations of safety and tolerability. Patients should expect their participation in this trial to last a minimum of 4 to 8 weeks. Their participation could continue for several months or beyond a year, depending on how their disease responds to the treatment. After completing study treatment, patients will be asked to attend for an End of Treatment visit and then a posttreatment Follow-up visit 4 to 6 weeks after stopping the medication. Patients will be randomly assigned to treatment with either 2.5 mg letrozole once daily plus placebo to match tipifarnib twice daily, or 2.5 mg letrozole once daily plus 300 mg tipifarnib twice daily. Both tipifranib and matching placebo will be given in 28-day cycles of 21 days of treatment followed by 7 days rest. All patients will receive continuous treatment with letrozole.

Eligibility criteria: Inclusion Criteria:

* Locally advanced, inoperable loco-regionally-recurrent, or metastatic breast cancer
* Estrogen and/or progesterone positive disease
* Progression of disease after antiestrogen therapy
* Measurable disease
* Postmenopausal
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.

Exclusion Criteria:

* Previous endocrine therapy, other than antiestrogen therapy
* More than 1 prior chemotherapy regimen
* Previous therapy with farnesyl transferase inhibitor
* Presence of rapidly progressive, life-threatening metastases
* Concomitant anticancer treatment
* Other malignancy within the past 5 years
* Symptomatic peripheral neuropathy.

Primary outcomes:
measure: Comparisons between the two treatment groups will be made for patients who have achieve a confirmed Complete Response (CR) or Partial Response (PR).
Secondary outcomes:
measure: Effectiveness will be assessed by time to disease progression; time to treatment failure; duration of response; clinical benefit; duration of clinical benefit; survival time. The study will include evaluations of safety and tolerability.
Other outcomes:
Locations:
city: Miami
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Durham
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Fort Worth
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Brussel
country: Belgium
city: Leuven
country: Belgium
city: Bordeaux Cedex
country: France
city: Clermont Ferrand Cedex 1
country: France
city: Montpellier Cedex 5 N/A
country: France
city: Rennes Cedex
country: France
city: Saint Herblain
country: France
city: Vandoeuvre Les Nancy
country: France
city: Den Haag
country: Netherlands
city: Moscow N/A
country: Russian Federation
city: Moscow
country: Russian Federation
city: St Petersburg N/A
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Huddersfield
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Johnston SR, Semiglazov VF, Manikhas GM, Spaeth D, Romieu G, Dodwell DJ, Wardley AM, Neven P, Bessems A, Park YC, De Porre PM, Perez Ruixo JJ, Howes AJ. A phase II, randomized, blinded study of the farnesyltransferase inhibitor tipifarnib combined with letrozole in the treatment of advanced breast cancer after antiestrogen therapy. Breast Cancer Res Treat. 2008 Jul;110(2):327-35. doi: 10.1007/s10549-007-9726-1. Epub 2007 Sep 13.