Clinical trial NCT01560416: Fulvestrant With or Without Ganetespib in HR+ Breast Cancer
Official title: Randomized Phase II Study of Fulvestrant With or Without Ganetespib in Patients With Hormone Receptor-Positive, Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Metastatic
HR positive
ER positive
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2012-03-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants were randomized 2:1 B Fulvestrant+Ganetespib:A Fulvestrant
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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 outcomes:
measure: Grade 3-4 Toxicity Rate
timeFrame: 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.
measure: Objective Response Rate (ORR)
timeFrame: 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.
measure: Clinical Benefit Rate (CBR)
timeFrame: 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.
measure: Overall Survival (OS)
timeFrame: 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.
Other outcomes:
Locations:
city: Boston
country: United States
facility: DFCI at Faulkner Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Concord
country: United States
facility: New Hampshire Oncology and Hematology, P.A.
state: New Hampshire
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Nancy U Lin, MD
role: PRINCIPAL_INVESTIGATOR
References: