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A Phase II Trial of Tipifarnib (R115777, Zarnestra™) in Combination With Fulvestrant (Faslodex®) in Postmenopausal Hormone Receptor-Positive Breast Cancer


Phase 2
18 Years
N/A
Not Enrolling
Female
Estrogen Receptor-positive Breast Cancer, Progesterone Receptor-positive Breast Cancer, Recurrent Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer

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Trial Information

A Phase II Trial of Tipifarnib (R115777, Zarnestra™) in Combination With Fulvestrant (Faslodex®) in Postmenopausal Hormone Receptor-Positive Breast Cancer


PRIMARY OBJECTIVES:

I. To determine the efficacy of tipifarnib (R115777, Zarnestra™) in combination with
fulvestrant based on clinical benefit rate (CBR, a combination of complete response rate,
partial response rate, and stable disease for more than 24 weeks) in postmenopausal women
with hormone receptor-positive metastatic breast cancer who have progressive disease after
first-line endocrine therapy.

SECONDARY OBJECTIVES:

I. To determine the median time to progression (TTP) and duration of response of tipifarnib
(R115777, Zarnestra™) in combination with fulvestrant in postmenopausal women with hormone
receptor-positive metastatic breast cancer.

II. To determine the median overall survival of tipifarnib (R115777, Zarnestra™) in
combination with fulvestrant in postmenopausal women with hormone receptor- positive
metastatic breast cancer who have progressive disease after first-line endocrine therapy.

III. To determine the toxicity profile of tipifarnib (R115777, Zarnestra™) in combination
with fulvestrant versus fulvestrant alone (from historical control) in postmenopausal women
with hormone receptor positive metastatic breast cancer who have progressive disease after
first-line endocrine therapy.

OUTLINE:

Patients receive fulvestrant intramuscularly on day 1 and oral tipifarnib twice daily on
days 1-21. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity*.

NOTE: *Fulvestrant continues even if tipifarnib is held for toxicity.

Patients are followed every 3 months.


Inclusion Criteria:



- Patients must have histologically or cytologically confirmed adenocarcinoma of the
breast

- Patients must be postmenopausal, defined as: (1) a history of at least 12 months
without spontaneous menstrual bleeding, (2) prior bilateral salpingo-oophorectomy,
with or without hysterectomy, (3) age >= 55 years with a prior hysterectomy with or
without oophorectomy, (4) age < 55 years with a prior hysterectomy without
oophorectomy or unknown status, with a documented FSH level in postmenopausal range
within 4 week s of registration, (5) receiving a gonadotropin releasing hormone
analog (GnRH) to suppress ovarian function (eg, goserelin 3.6 mg q 4 weeks)

- Patients must have stage IV disease or inoperable locally advanced disease

- Patients must have ER- and/or PR-positive disease as determined by their local
pathology laboratory

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
20 mm with conventional techniques or as >= 10 mm with spiral CT scan; all sites of
disease should be noted and followed

- Prior hormonal therapy as adjuvant therapy and/or for metastatic disease is
permitted; patients previously treated with two or more prior doses of fulvestrant
are not eligible; patients who have received one prior dose of fulvestrant within 28
days are eligible so long as they meet other eligibility criteria

- Patients must have ECOG performance status 0-2 (Karnofsky >= 60%)

- Patients must have life expectancy of greater than 3 months

- Leukocytes >= 3,000/uL

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- Total bilirubin =< 2 mg/dL

- AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal

- Creatinine less than or equal to 1.5 times the institutional upper limits of normal

- Patients must be disease-free of prior invasive malignancies for >= 5 years with the
exception of: curatively-treated basal cell or squamous cell carcinoma of the skin,
carcinoma in situ of the cervix

- Patients must have the ability to understand and the willingness to sign a written
informed consent document

- Patients who have had previous therapy with farnesyltransferase inhibitor

Exclusion Criteria:

- Patients who have had radiotherapy within 4 weeks prior to entering the study or
those who have not recovered from adverse events due to agents administered more than
4 weeks earlier; patients who have had prior chemotherapy for metastatic disease are
not eligible; prior adjuvant or neoadjuvant chemotherapy is allowed

- Patients may not be receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to tipifarnib (R115777, Zarnestra™) or other agents used in the study
(e.g., imidazoles, quinolones)

- Presence of rapidly progressive, life-threatening metastases; this includes patients
with extensive hepatic involvement (> 50% of the liver involved), symptomatic
lymphangitic metastases, or brain or eptomeningeal involvement

- Concomitant anticancer treatment with the following exceptions: (1) bisphosphonates
for bone metastases, (2) a GnRH analog is permitted if the patient had progressive
disease on a GnRH analog plus a SERM or an AI; the GnRH analog may continue but the
SERM or AI must be discontinued

- Grade 2 or more peripheral neuropathy

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study because of possible pharmacokinetic interactions with tipifarnib or other
agents administered during the study.; appropriate studies will be undertaken in
patients receiving combination anti-retroviral therapy when indicated

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical benefit rate (CBR) (CR rate, PR rate, and SD)

Outcome Time Frame:

Up to 24 weeks

Safety Issue:

No

Principal Investigator

Linda Vahdat

Investigator Role:

Principal Investigator

Investigator Affiliation:

Montefiore Medical Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02982

NCT ID:

NCT00082810

Start Date:

March 2004

Completion Date:

Related Keywords:

  • Estrogen Receptor-positive Breast Cancer
  • Progesterone Receptor-positive Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms

Name

Location

Montefiore Medical CenterBronx, New York  10467-2490