Fulvestrant With or Without Ganetespib in HR+ Breast Cancer

Breast Cancer Clinical Trial

Official title:

Randomized Phase II Study of Fulvestrant With or Without Ganetespib in Patients With Hormone Receptor-Positive, Metastatic Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01560416
• Other study ID #: 11-477
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 2012
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ganetespib is a drug that may stop cancer cells from growing. This drug has been used in other research studies and laboratory experiments. It has also been studied in phase I trials, where the appropriate dosing has been determined. Ganetespib is considered an "HSP90 inhibitor". By blocking HSP90, ganetespib is thought to reduce the ability of cancer cells to become resistant to treatment.

Fulvestrant is a hormonal therapy that works by attaching to estrogen receptors. In doing so, it can block the effect of estrogen on cancer cells. In addition, fulvestrant causes a decrease in the number of estrogen receptors. Fulvestrant is a drug that is approved by the FDA for treatment of metastatic, hormone receptor positive breast cancer, based upon the results of phase III clinical trials.

In the laboratory, adding ganetespib to fulvestrant appears to improve its effectiveness. It is not known whether this is true in humans. In this research study, we are evaluating the effect of the addition of ganetespib to fulvestrant in participants with hormone receptor-positive, metastatic breast cancer.

Description:

Because no one knows which of the study options is best, you will be "randomized" into one of the study groups: Arm A: Fulvestrant or Arm B: Fulvestrant plus Ganetespib. You will have a one-third chance of being placed in Arm A and a two-thirds chance of being placed in Arm B.

If you are initially placed in Arm A but your disease progresses, you will have the option of receiving the combination of fulvestrant plus ganetespib as part of Arm C.

You will undergo the following procedures during the research study: study drug(s), blood tests, clinical exams and scans/imaging tests.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: December 2024
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed invasive breast cancer that is metastatic or unresectable locally advanced

• Estrogen and/or progesterone receptor positive breast cancer

• HER2 negative

• Measurable disease is required (effective 4/30/14: all non-measurable [evaluable] disease slots have been filled)

• Endocrine resistant breast cancer

• May have received up to one prior line of chemotherapy for metastatic or unresectable locally advanced breast cancer

• May have initiated bisphosphonate therapy prior to start of protocol therapy

• Must be at least 2 weeks from prior chemotherapy or radiotherapy

• ECOG performance status of 0 or 1

• Availability of tissue block from initial breast cancer diagnosis and/or metastatic recurrence

• For subjects with biopsy-accessible disease, must be willing to undergo a required on-treatment research biopsy

• Adequate IV access

Exclusion Criteria:

• Pregnant or breastfeeding

• Prior treatment with HSP90 inhibitor

• Prior treatment with fulvestrant

• Concurrent treatment with commercial agents or other agents with the intent to treat the participant's malignancy

• Untreated or progressive brain metastases

• Pending visceral crisis, in the opinion of the treating investigator

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to fulvestrant or ganetespib

• Uncontrolled intercurrent illness

• Other malignancies within 3 years

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Fulvestrant

• Ganetespib

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	DFCI at Faulkner Hospital	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	New Hampshire Oncology and Hematology, P.A.	Concord	New Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	PFS based on Kaplan-Meier is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD are censored at the date of last disease assessment. Participants who receive non-protocol anti-cancer therapy before disease progression are censored at time of last disease assessment.	Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles longer-term. Participants in this study cohort were followed for survival up to 4 years from treatment end.
Secondary	Grade 3-4 Toxicity Rate	All grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms were counted to calculate the percentage of participants experiencing at least one treatment-related grade 3 or 4 AE of any type on treatment.	AEs were assessed every cycle on treatment (weeks 2-3 on cycle 1). Median treatment duration was 4 cycles/~4 months on each arm. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months.
Secondary	Objective Response Rate (ORR)	ORR was defined as the percentage of participants with measurable disease at baseline achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.	Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles thereafter on treatment. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months.
Secondary	Clinical Benefit Rate (CBR)	CBR was defined as the percentage of participants with measurable disease at baseline achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria. SD needed to be a minimum 24 weeks in duration.	Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles thereafter on treatment. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months.
Secondary	Overall Survival (OS)	OS based on Kaplan-Meier is defined as the time from study entry to death or date last known alive or censored at date last known alive.	Participants were followed long-term for survival every 3 months from the end of treatment until death, lost to follow-up or up to 4 years from treatment end. Median survival follow-up was 28 months for the study cohort.