Tipifarnib and Fulvestrant in Hormone Receptor-Positive Metastatic Breast Cancer

NCT00082810 | Completed Phase 2 Results DMC

• 3 other identifiers: NCI-2012-029826205N01CM62204
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial is studying how well giving tipifarnib together with fulvestrant works as second-line therapy in treating postmenopausal women with hormone receptor-positive inoperable locally advanced or metastatic breast cancer that has progressed after previous first-line endocrine therapy. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen. Combining tipifarnib with fulvestrant may kill tumor cells that did not respond to first-line therapy.

Conditions

Estrogen Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR) (CR Rate, PR Rate, and SD)

  Number of participants met the definition of Clinical Benefit Rate.Tumor response was assessed every three cycles by CT using RECIST (Response Evaluation Criteria In Solid Tumors) criteria. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

  Up to 24 weeks

Secondary Outcomes (4)

• Time to Progression (TTP)

  From randomization until progression of the disease, assessed up to 4 years

• Duration of Response

  Up to 4 years

• Toxicity as Assessed by NCI CTCAE Version 3.0

  Up to 4 years

• Median Overall Survival

  From randomization until death or censored at the date of last follow-up, assessed up to 4 years

Study Arms (1)

Treatment (tipifarnib, fulvestrant)

EXPERIMENTAL

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\*.

Drug: fulvestrant; Drug: tipifarnib

Interventions

fulvestrant DRUG

Given intramuscularly

Also known as: Faslodex, ICI 182,780

Treatment (tipifarnib, fulvestrant)

tipifarnib DRUG

Given IV

Also known as: R115777, Zarnestra

Treatment (tipifarnib, fulvestrant)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed adenocarcinoma of the breast
• Patients must be postmenopausal
• 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

You may not qualify if:

• 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 leptomeningeal 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467-2490, United States

Location

Related Publications (1)

• Li T, Christos PJ, Sparano JA, Hershman DL, Hoschander S, O'Brien K, Wright JJ, Vahdat LT. Phase II trial of the farnesyltransferase inhibitor tipifarnib plus fulvestrant in hormone receptor-positive metastatic breast cancer: New York Cancer Consortium Trial P6205. Ann Oncol. 2009 Apr;20(4):642-7. doi: 10.1093/annonc/mdn689. Epub 2009 Jan 19.

  PMID: 19153124 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; tipifarnib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: NYCC Regulatory Coordinator
• Organization: Montefiore Medical Center - New York

sforde@montefiore.org

718-379-6862

Study Officials

• Linda Vahdat

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2004
• First Posted: May 19, 2004
• Study Start: March 1, 2004
• Primary Completion: July 1, 2008
• Study Completion: September 1, 2008
• Last Updated: November 1, 2018
• Results First Posted: August 10, 2015

Record last verified: 2018-10

Locations

US (1)