Fulvestrant With or Without Ganetespib in HR+ Breast Cancer

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01560416
• Collaborator: (none)
• Enrollment: 50
• Locations: 5
• Arms: 2
• Duration (Months): 49
• Patients Per Site: 10
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Fulvestrant; Drug: Ganetespib	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants were randomized 2:1 B Fulvestrant+Ganetespib:A FulvestrantParticipants were randomized 2:1 B Fulvestrant+Ganetespib:A Fulvestrant
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Study of Fulvestrant With or Without Ganetespib in Patients With Hormone Receptor-Positive, Metastatic Breast Cancer
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ARM A - Fulvestrant 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.	Drug: Fulvestrant; Other Names: Faslodex
Active Comparator: Arm B - Fulvestrant+Ganetespib 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.	Drug: Fulvestrant; Other Names: Faslodex ; Drug: Ganetespib; Other Names: STA9090

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [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.]

   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

1. Grade 3-4 Toxicity Rate [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.]

   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.

2. Objective Response Rate (ORR) [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.]

   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.

3. Clinical Benefit Rate (CBR) [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.]

   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.

4. Overall Survival (OS) [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.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	DFCI at Faulkner Hospital	Boston	Massachusetts	United States	02130
2	Brigham and Women's Hospital	Boston	Massachusetts	United States	02215
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
4	New Hampshire Oncology and Hematology, P.A.	Concord	New Hampshire	United States	03301
5	University of North Carolina	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• Dana-Farber Cancer Institute

Investigators

• Principal Investigator: Nancy U Lin, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 14, 2015

More Information

Publications

None provided.

• Responsible Party: Nancy Lin, MD, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT01560416
• Other Study ID Numbers: 11-477
• First Posted: Mar 22, 2012
• Last Update Posted: Jan 3, 2019
• Last Verified: Dec 1, 2018

• Keywords provided by Nancy Lin, MD, Principal Investigator, Dana-Farber Cancer Institute: Metastatic; HR positive; ER positive
• Additional relevant MeSH terms: Breast Neoplasms; Fulvestrant

Study Results

Participant Flow

Recruitment Details	Participants were enrolled between June 2012 and June 2015

Arm/Group Title	ARM A - Fulvestrant	Arm B - Fulvestrant+Ganetespib
Arm/Group 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.
Period Title: Randomized Phase
STARTED	15	35
COMPLETED	8	35
NOT COMPLETED	7	0
Period Title: Randomized Phase
STARTED	7	0
COMPLETED	7	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	ARM A - Fulvestrant	Arm B - Fulvestrant+Ganetespib	Total
Arm/Group 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.	Total of all reporting groups
Overall Participants	15	35	50
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	14 93.3%	29 82.9%	43 86%
>=65 years	1 6.7%	6 17.1%	7 14%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57	52	53
Sex: Female, Male (Count of Participants)
Female	15 100%	34 97.1%	49 98%
Male	0 0%	1 2.9%	1 2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 2.9%	1 2%
Not Hispanic or Latino	15 100%	34 97.1%	49 98%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 5.7%	2 4%
White	15 100%	30 85.7%	45 90%
More than one race	0 0%	1 2.9%	1 2%
Unknown or Not Reported	0 0%	2 5.7%	2 4%
Region of Enrollment (Count of Participants)
United States	15 100%	35 100%	50 100%

Outcome Measures

1. Primary Outcome

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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ARM A - Fulvestrant	Arm B - Fulvestrant+Ganetespib
Arm/Group 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.
Measure Participants	15	35
Mean (95% Confidence Interval) [months]	3.7	3.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ARM A - Fulvestrant, Arm B - Fulvestrant+Ganetespib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ARM A - Fulvestrant	Arm B - Fulvestrant+Ganetespib	Arm A - Crossover Fulvestrant+Ganetespib
Arm/Group 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.	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 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.
Measure Participants	15	35	7
Number [percentage of participants]	100 666.7%	100 285.7%	100 200%

3. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all enrolled participants.

Arm/Group Title	ARM A - Fulvestrant	Arm B - Fulvestrant+Ganetespib
Arm/Group 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.
Measure Participants	15	35
Number (95% Confidence Interval) [percentage of participants]	20.0 133.3%	14.3 40.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ARM A - Fulvestrant, Arm B - Fulvestrant+Ganetespib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all enrolled participants.

Arm/Group Title	ARM A - Fulvestrant	Arm B - Fulvestrant+Ganetespib
Arm/Group 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.
Measure Participants	15	35
Number (95% Confidence Interval) [percentage of participants]	33.3 222%	34.3 98%

5. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all enrolled participants.

Arm/Group Title	ARM A - Fulvestrant	Arm B - Fulvestrant+Ganetespib
Arm/Group 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.
Measure Participants	15	35
Median (95% Confidence Interval) [months]	25.9	29.2

Adverse Events

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.
Arm/Group Title	ARM A - Fulvestrant		Arm B - Fulvestrant+Ganetespib		Arm A - Crossover Fulvestrant+Ganetespib
Arm/Group 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.		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 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.
All Cause Mortality
	ARM A - Fulvestrant		Arm B - Fulvestrant+Ganetespib		Arm A - Crossover Fulvestrant+Ganetespib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/15 (73.3%)		15/35 (42.9%)		6/7 (85.7%)
Serious Adverse Events
	ARM A - Fulvestrant		Arm B - Fulvestrant+Ganetespib		Arm A - Crossover Fulvestrant+Ganetespib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)		11/35 (31.4%)		0/7 (0%)
Cardiac disorders
Sinus Tachycardia	0/15 (0%)	0	1/35 (2.9%)	1	0/7 (0%)	0
Acute coronary syndrome	0/15 (0%)	0	1/35 (2.9%)	1	0/7 (0%)	0
Gastrointestinal disorders
Obstruction Gastric	0/15 (0%)	0	1/35 (2.9%)	2	0/7 (0%)	0
Vomiting	0/15 (0%)	0	3/35 (8.6%)	7	0/7 (0%)	0
Hemorrhoids	0/15 (0%)	0	1/35 (2.9%)	1	0/7 (0%)	0
Nausea	0/15 (0%)	0	3/35 (8.6%)	6	0/7 (0%)	0
Duodenal ulcer	0/15 (0%)	0	1/35 (2.9%)	5	0/7 (0%)	0
Hepatobiliary disorders
Hepatic pain	0/15 (0%)	0	1/35 (2.9%)	1	0/7 (0%)	0
Infections and infestations
Infections and infestations-other	0/15 (0%)	0	1/35 (2.9%)	2	0/7 (0%)	0
Investigations
Lipase Increased	0/15 (0%)	0	1/35 (2.9%)	2	0/7 (0%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity	1/15 (6.7%)	1	0/35 (0%)	0	0/7 (0%)	0
Nervous system disorders
Peripheral motor neuropathy	0/15 (0%)	0	1/35 (2.9%)	1	0/7 (0%)	0
Dizziness	0/15 (0%)	0	1/35 (2.9%)	1	0/7 (0%)	0
Vasovagal reaction	0/15 (0%)	0	1/35 (2.9%)	1	0/7 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/15 (6.7%)	1	0/35 (0%)	0	0/7 (0%)	0
Cough	1/15 (6.7%)	1	0/35 (0%)	0	0/7 (0%)	0
Skin and subcutaneous tissue disorders
Rash maculopapular	0/15 (0%)	0	1/35 (2.9%)	2	0/7 (0%)	0
Vascular disorders
Hematoma	0/15 (0%)	0	1/35 (2.9%)	1	0/7 (0%)	0
Thromboembolic event	0/15 (0%)	0	1/35 (2.9%)	1	0/7 (0%)	0
Other (Not Including Serious) Adverse Events
	ARM A - Fulvestrant		Arm B - Fulvestrant+Ganetespib		Arm A - Crossover Fulvestrant+Ganetespib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/15 (100%)		35/35 (100%)		7/7 (100%)
Blood and lymphatic system disorders
anemia	0/15 (0%)	0	3/35 (8.6%)	3	0/7 (0%)	0
Gastrointestinal disorders
Diarrhea	1/15 (6.7%)	1	34/35 (97.1%)	34	6/7 (85.7%)	6
nausea	6/15 (40%)	6	22/35 (62.9%)	22	1/7 (14.3%)	1
constipation	7/15 (46.7%)	7	8/35 (22.9%)	8	0/7 (0%)	0
gastroesophageal reflux disease	2/15 (13.3%)	2	6/35 (17.1%)	6	0/7 (0%)	0
gastrointestinal disorders-other	0/15 (0%)	0	5/35 (14.3%)	5	0/7 (0%)	0
General disorders
fatigue	9/15 (60%)	9	23/35 (65.7%)	23	2/7 (28.6%)	2
pain	4/15 (26.7%)	4	8/35 (22.9%)	8	2/7 (28.6%)	2
injection site reaction	4/15 (26.7%)	4	3/35 (8.6%)	3	0/7 (0%)	0
non-cardiac chest pain	2/15 (13.3%)	2	3/35 (8.6%)	3	0/7 (0%)	0
Infections and infestations
infections and infestations-other	1/15 (6.7%)	1	1/35 (2.9%)	1	0/7 (0%)	0
Investigations
aspartate aminotransferase increased	2/15 (13.3%)	2	5/35 (14.3%)	5	1/7 (14.3%)	1
alanine aminotransferase increased	1/15 (6.7%)	1	4/35 (11.4%)	4	1/7 (14.3%)	1
alkaline phosphatase increased	2/15 (13.3%)	2	2/35 (5.7%)	2	0/7 (0%)	0
Metabolism and nutrition disorders
anorexia	2/15 (13.3%)	2	5/35 (14.3%)	5	1/7 (14.3%)	1
hypophosphatemia	0/15 (0%)	0	1/35 (2.9%)	1	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
back pain	2/15 (13.3%)	2	11/35 (31.4%)	11	0/7 (0%)	0
pain in extremity	5/15 (33.3%)	5	8/35 (22.9%)	8	0/7 (0%)	0
arthralgia	4/15 (26.7%)	4	4/35 (11.4%)	4	0/7 (0%)	0
bone pain	6/15 (40%)	6	2/35 (5.7%)	2	0/7 (0%)	0
neck pain	3/15 (20%)	3	2/35 (5.7%)	2	0/7 (0%)	0
Nervous system disorders
headache	3/15 (20%)	3	10/35 (28.6%)	10	0/7 (0%)	0
peripheral sensory neuropathy	2/15 (13.3%)	2	4/35 (11.4%)	4	0/7 (0%)	0
dysgeusia	2/15 (13.3%)	2	2/35 (5.7%)	2	0/7 (0%)	0
Psychiatric disorders
insomnia	2/15 (13.3%)	2	9/35 (25.7%)	9	2/7 (28.6%)	2
anxiety	1/15 (6.7%)	1	6/35 (17.1%)	6	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
dyspnea	3/15 (20%)	3	6/35 (17.1%)	6	0/7 (0%)	0
cough	1/15 (6.7%)	1	5/35 (14.3%)	5	0/7 (0%)	0
Skin and subcutaneous tissue disorders
rash acneiform	2/15 (13.3%)	2	3/35 (8.6%)	3	1/7 (14.3%)	1
Vascular disorders
hot flashes	6/15 (40%)	6	8/35 (22.9%)	8	0/7 (0%)	0
hypertension	1/15 (6.7%)	1	2/35 (5.7%)	2	0/7 (0%)	0
hematoma	1/15 (6.7%)	1	1/35 (2.9%)	1	0/7 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.