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Fulvestrant With or Without Ganetespib in HR+ Breast Cancer

Primary Purpose

Breast Cancer

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fulvestrant
Ganetespib
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Metastatic, HR positive, ER positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • DFCI at Faulkner Hospital
  • Brigham and Women's Hospital
  • Dana-Farber Cancer Institute
  • New Hampshire Oncology and Hematology, P.A.
  • University of North Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

ARM A - Fulvestrant

Arm B - Fulvestrant+Ganetespib

Arm Description

Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Eligible participants on Arm A were allowed to crossover to Arm B upon disease progression. Treatment continued for Arm A participants until 2nd disease progression.

Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Ganetespib: 200 mg/m2 administered intravenously on days 1, 8 and 15 of each 28 day cycle Arm B participants whose disease was at a minimum stable could elect to discontinue ganetespib after 6 cycles or stay on combination treatment until disease progression. Otherwise, Arm B participants taken off ganetespib for toxicity were to remain on single agent fulvestrant until disease progression.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
February 21, 2012
Last Updated
September 25, 2023
Sponsor
Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT01560416
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 2012 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Metastatic, HR positive, ER positive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Participants were randomized 2:1 B Fulvestrant+Ganetespib:A Fulvestrant
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ARM A - Fulvestrant
Arm Type
Active Comparator
Arm Description
Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Eligible participants on Arm A were allowed to crossover to Arm B upon disease progression. Treatment continued for Arm A participants until 2nd disease progression.
Arm Title
Arm B - Fulvestrant+Ganetespib
Arm Type
Active Comparator
Arm Description
Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Ganetespib: 200 mg/m2 administered intravenously on days 1, 8 and 15 of each 28 day cycle Arm B participants whose disease was at a minimum stable could elect to discontinue ganetespib after 6 cycles or stay on combination treatment until disease progression. Otherwise, Arm B participants taken off ganetespib for toxicity were to remain on single agent fulvestrant until disease progression.
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Other Intervention Name(s)
Faslodex
Intervention Type
Drug
Intervention Name(s)
Ganetespib
Other Intervention Name(s)
STA9090
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Grade 3-4 Toxicity Rate
Description
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.
Time Frame
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.
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
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.
Title
Clinical Benefit Rate (CBR)
Description
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.
Time Frame
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.
Title
Overall Survival (OS)
Description
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.
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy U Lin, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
DFCI at Faulkner Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02130
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
New Hampshire Oncology and Hematology, P.A.
City
Concord
State/Province
New Hampshire
ZIP/Postal Code
03301
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

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Fulvestrant With or Without Ganetespib in HR+ Breast Cancer

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