Hsp90 Inhibitor STA-9090 in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy

• Sponsor: Barbara Ann Karmanos Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01270880
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 18
• Locations: 4
• Arm: 1
• Duration (Months): 42
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Hsp90 inhibitor STA-9090 may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. This phase II trial is studying how well Hsp90 inhibitor STA-9090 works in treating patients with metastatic hormone-resistant prostate cancer previously treated with docetaxel-based chemotherapy

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage IV Prostate Cancer	Drug: Hsp90 inhibitor STA-9090; Other: laboratory biomarker analysis; Genetic: polymerase chain reaction; Other: enzyme-linked immunosorbent assay; Genetic: RNA analysis; Other: spectrophotometry; Genetic: reverse transcriptase-polymerase chain reaction; Genetic: gene expression analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate progression-free survival (PFS) achieved with STA-9090 (Hsp90 inhibitor STA-9090) in men with castration-resistant prostate cancer (CRPC) who have received prior docetaxel based therapy.

SECONDARY OBJECTIVES:

1. To assess the percentage change in prostate-specific antigen (PSA) from baseline to 12 weeks.

2. To assess overall safety and tolerability of STA-9090. III. To evaluate overall survival (OS) outcome in metastatic CRPC who have received prior docetaxel therapy.

3. To investigate the association of progression-free survival (PFS) and PSA response rate with primary and secondary target markers.

TERTIARY OBJECTIVES:

1. To evaluate potential markers for predicting drug response or efficacy, blood samples will be used to collect the serum and extract messenger ribonucleic acid (mRNA) from mononuclear cells and analyzed by quantitative real-time polymerase chain reaction (PCR) and/or enzyme-linked immunosorbent assay (ELISA).

OUTLINE:

Patients receive Hsp90 inhibitor STA-9090 intravenously (IV) over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of STA-9090 in Patients With Metastatic Castration-Resistant Prostate Cancer (CRPC) Pretreated With Docetaxel Based Chemotherapy
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (enzyme inhibitor therapy) Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Hsp90 inhibitor STA-9090; Given IV; Other Names: STA-9090 ; Other: laboratory biomarker analysis; Correlative studies; Genetic: polymerase chain reaction; Correlative studies; Other Names: PCR ; Other: enzyme-linked immunosorbent assay; Correlative studies; Other Names: ELISA ; Genetic: RNA analysis; Correlative studies; Other: spectrophotometry; Correlative studies; Genetic: reverse transcriptase-polymerase chain reaction; Correlative studies; Other Names: RT-PCR ; Genetic: gene expression analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. PFS Proportion Achieved With STA-9090 in Men With CRPC Who Have Received Prior Docetaxel Based Therapy [At 6 months]

   Our primary objective was to determine the 6-month PFS rate by using a binary (yes/no) endpoint of 6 months of PFS. Treatment success was defined as achievement of at least 6 months of PFS. Patients who did not complete 6 months of ganetespib therapy for any reason (including death from any cause) were considered treatment failures and were recorded as not achieving the primary endpoint.

Secondary Outcome Measures

1. Percentage Change in PSA [From baseline to 12 weeks]

   Percentage change in PSA from baseline.

2. Overall Safety and Tolerability of STA-9090 [Day 1, 8, and 15 of each course and at end of treatment]

   Overall safety and tolerability of STA-9090 by total number of grade 3 adverse events

3. OS in Metastatic CRPC Who Have Received Prior Docetaxel Therapy [From first dose to death or the date last known alive]

   Overall Survival (OS) in metastatic Castrate Resistant Prostate Cancer (CRPC) who have received prior docetaxel therapy using Kaplan-Meier method

4. Association of PFS With PSA [At 6 months]

   Association of PFS with PSA using Cox PH regression model

5. Potential Markers for Predicting Drug Response or Efficacy [At baseline, day 1 of course 3, and end of treatment]

   Potential markers for predicting drug response or efficacy : This is not a measurable outcome, but a possible entity for further study.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Pathologically confirmed diagnosis of prostate adenocarcinoma with metastasis and objective progression or rising PSA despite androgen deprivation therapy and antiandrogen withdrawal when applicable

• Progression after docetaxel based chemotherapy is needed as follows:

• 1. If measurable disease present, then either rising PSA, increase in size of the lesion/s or both should be present
• 1. Patients with rising PSA only as progression must demonstrate a rising trend with 2 successive elevations at minimum intervals of 1 week; a minimum PSA of 5 ng/ml, or new areas of bony metastases on bone scan are required for patients with no measurable disease; no minimum PSA requirement for patients with measurable disease

• Patients should have received at least one prior docetaxel based regimen for metastatic disease; no maximum prior therapy

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2

• Life expectancy of at least 3 months

• Prior radiation therapy or chemotherapy completed at least 28 days prior to enrollment

• All patients must be documented to be castrate with a testosterone level =< 0.5 ng/ml; luteinizing-hormone-releasing hormone (LHRH) agonist therapy must be continued, if required to maintain castrate levels of testosterone; patients must be off antiandrogens for a minimum of 4 weeks for flutamide and 6 weeks for bicalutamide or nilutamide

• Absolute neutrophil count >= 1,500 cells/uL

• Platelets >= 100,000/uL

• Hemoglobin >= 9.0 g/dL

• Serum creatinine =< 1.5 x upper limit of normal (ULN); Note: if serum creatinine is > 1.5 x ULN, subject is eligible if the calculated creatinine clearance (CLcr) is >= 50 mL/min

• Total bilirubin =< 1.5 x ULN

• For patients without documented bone metastases or for patients with liver metastases: transaminases (aspartate aminotransferase [AST]/serum glutamic oxaloacetic transaminase [SGOT] and/or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase [SGPT]) may be up to 2.5 x institutional ULN if alkaline phosphatase is =< ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are =< ULN

• For patients with documented bone metastases, the transaminases (AST/SGOT and/or ALT/SGPT) should be less than 2.5 x institutional ULN, without regard to the alkaline phosphatase level

• Sexually active males must use measures to prevent pregnancy in their partners while on STA-9090

• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

• Major surgery within 4 weeks prior to first dose of STA-9090

• Poor venous access for study drug administration or would require a peripheral or central indwelling catheter for study drug administration; study drug administration via indwelling catheters is prohibited at this time

• Use of any chemotherapy or other standard systemic treatments for prostate cancer, including investigational agents within 2 weeks or 6 half- lives of the agent, whichever is shorter, prior to receiving STA-9090; there must be at least 2 weeks between the end of palliative radiation and the start of study drug and all radiation therapy (XRT)-associated toxicities resolved to Grade 1 or 0

• History of severe allergic or hypersensitivity reactions to excipients (e.g., Polyethylene glycol [PEG] 300 and Polysorbate 80 [i.e. docetaxel])

• Baseline QTc > 450 msec or previous history of QT prolongation while taking other medications

• Ventricular ejection fraction (Ef) =< 55% at baseline

• Any history of current coronary artery disease, myocardial infarction, angina pectoris, angioplasty or coronary bypass surgery

• History of current uncontrolled dysrhythmias, or requirement for antiarrhythmic medications, or Grade 2 or greater left bundle branch block

• New York Heart Association class II/III/IV congestive heart failure with a history of dyspnea, orthopnea, or edema that requires current treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers or diuretics

• Current or prior radiation therapy to the left hemithorax

• Treatment with chronic immunosuppressants (e.g. cyclosporine following transplantation)

• Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital	Baltimore	Maryland	United States	21231
2	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
3	University of Medicine nd Denistry of New Jersey	Piscataway	New Jersey	United States	08854
4	University of Wisconsin Cancer Center Riverview	Wisconsin Rapids	Wisconsin	United States	54494

Sponsors and Collaborators

• Barbara Ann Karmanos Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Elisabeth Heath, Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elisabeth Heath, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT01270880
• Other Study ID Numbers: 2010-070; NCI-2010-02328
• First Posted: Jan 5, 2011
• Last Update Posted: Sep 18, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	Treatment (Enzyme Inhibitor Therapy)
Arm/Group Description	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Hsp90 inhibitor STA-9090: Given IV laboratory biomarker analysis: Correlative studies polymerase chain reaction: Correlative studies enzyme-linked immunosorbent assay: Correlative studies RNA analysis: Correlative studies spectrophotometry: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies gene expression analysis: Correlative studies
Period Title: Overall Study
STARTED	18
COMPLETED	17
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Enzyme Inhibitor Therapy)
Arm/Group Description	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Hsp90 inhibitor STA-9090: Given IV laboratory biomarker analysis: Correlative studies polymerase chain reaction: Correlative studies enzyme-linked immunosorbent assay: Correlative studies RNA analysis: Correlative studies spectrophotometry: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies gene expression analysis: Correlative studies
Overall Participants	18
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	18 100%
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

Title	PFS Proportion Achieved With STA-9090 in Men With CRPC Who Have Received Prior Docetaxel Based Therapy
Description	Our primary objective was to determine the 6-month PFS rate by using a binary (yes/no) endpoint of 6 months of PFS. Treatment success was defined as achievement of at least 6 months of PFS. Patients who did not complete 6 months of ganetespib therapy for any reason (including death from any cause) were considered treatment failures and were recorded as not achieving the primary endpoint.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor Therapy)
Arm/Group Description	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Hsp90 inhibitor STA-9090: Given IV laboratory biomarker analysis: Correlative studies polymerase chain reaction: Correlative studies enzyme-linked immunosorbent assay: Correlative studies RNA analysis: Correlative studies spectrophotometry: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies gene expression analysis: Correlative studies
Measure Participants	18
Number (90% Confidence Interval) [proportion with 6+ months PFS]	0.0

2. Secondary Outcome

Title	Percentage Change in PSA
Description	Percentage change in PSA from baseline.
Time Frame	From baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor Therapy)
Arm/Group Description	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Hsp90 inhibitor STA-9090: Given IV laboratory biomarker analysis: Correlative studies polymerase chain reaction: Correlative studies enzyme-linked immunosorbent assay: Correlative studies RNA analysis: Correlative studies spectrophotometry: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies gene expression analysis: Correlative studies
Measure Participants	18
Median (Full Range) [percentage change from baseline PSA]	78.65

3. Secondary Outcome

Title	Overall Safety and Tolerability of STA-9090
Description	Overall safety and tolerability of STA-9090 by total number of grade 3 adverse events
Time Frame	Day 1, 8, and 15 of each course and at end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor Therapy)
Arm/Group Description	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Hsp90 inhibitor STA-9090: Given IV laboratory biomarker analysis: Correlative studies polymerase chain reaction: Correlative studies enzyme-linked immunosorbent assay: Correlative studies RNA analysis: Correlative studies spectrophotometry: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies gene expression analysis: Correlative studies
Measure Participants	18
Number [events of grade 3+ toxicity]	35

4. Secondary Outcome

Title	OS in Metastatic CRPC Who Have Received Prior Docetaxel Therapy
Description	Overall Survival (OS) in metastatic Castrate Resistant Prostate Cancer (CRPC) who have received prior docetaxel therapy using Kaplan-Meier method
Time Frame	From first dose to death or the date last known alive

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor Therapy)
Arm/Group Description	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Hsp90 inhibitor STA-9090: Given IV laboratory biomarker analysis: Correlative studies polymerase chain reaction: Correlative studies enzyme-linked immunosorbent assay: Correlative studies RNA analysis: Correlative studies spectrophotometry: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies gene expression analysis: Correlative studies
Measure Participants	18
Median (90% Confidence Interval) [months]	12.5

5. Secondary Outcome

Title	Association of PFS With PSA
Description	Association of PFS with PSA using Cox PH regression model
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor Therapy)
Arm/Group Description	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Hsp90 inhibitor STA-9090: Given IV laboratory biomarker analysis: Correlative studies polymerase chain reaction: Correlative studies enzyme-linked immunosorbent assay: Correlative studies RNA analysis: Correlative studies spectrophotometry: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies gene expression analysis: Correlative studies
Measure Participants	18
Number (95% Confidence Interval) [Hazard Ratio]	1.000

6. Secondary Outcome

Title	Potential Markers for Predicting Drug Response or Efficacy
Description	Potential markers for predicting drug response or efficacy : This is not a measurable outcome, but a possible entity for further study.
Time Frame	At baseline, day 1 of course 3, and end of treatment

Outcome Measure Data

Analysis Population Description

No data was collected for this outcome.

Arm/Group Title	Treatment (Enzyme Inhibitor Therapy)
Arm/Group Description	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Hsp90 inhibitor STA-9090: Given IV laboratory biomarker analysis: Correlative studies polymerase chain reaction: Correlative studies enzyme-linked immunosorbent assay: Correlative studies RNA analysis: Correlative studies spectrophotometry: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies gene expression analysis: Correlative studies
Measure Participants	0

Adverse Events

Arm/Group Title	Treatment (Enzyme Inhibitor Therapy)
Arm/Group Description	Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Hsp90 inhibitor STA-9090: Given IV laboratory biomarker analysis: Correlative studies polymerase chain reaction: Correlative studies enzyme-linked immunosorbent assay: Correlative studies RNA analysis: Correlative studies spectrophotometry: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies gene expression analysis: Correlative studies
All Cause Mortality
	Treatment (Enzyme Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Enzyme Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	10/18 (55.6%)
Blood and lymphatic system disorders
Anemia	1/18 (5.6%)	1
Gastrointestinal disorders
Abdominal pain	2/18 (11.1%)	2
Diarrhea	3/18 (16.7%)	3
Nausea	2/18 (11.1%)	2
Vomiting	2/18 (11.1%)	2
Constipation	1/18 (5.6%)	1
Enterocolitis	1/18 (5.6%)	1
General disorders
Fatigue	3/18 (16.7%)	3
Non-cardiac chest pain	1/18 (5.6%)	1
Injury, poisoning and procedural complications
Hip fracture	1/18 (5.6%)	1
Investigations
Alkaline phosphatase increased	4/18 (22.2%)	4
Aspartate aminotransferase increased	2/18 (11.1%)	2
Lymphocyte count decreased	1/18 (5.6%)	1
Blood bilirubin increased	1/18 (5.6%)	1
Platelet count decreased	1/18 (5.6%)	1
Investigations, other	1/18 (5.6%)	1
Metabolism and nutrition disorders
Dehydration	3/18 (16.7%)	3
Hyperkalemia	1/18 (5.6%)	1
Hypoalbuminemia	1/18 (5.6%)	1
Hyponatremia	1/18 (5.6%)	1
Hypocalcemia	1/18 (5.6%)	1
Hypophosphatemia	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Enzyme Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	17/18 (94.4%)
Blood and lymphatic system disorders
Anemia	5/18 (27.8%)	5
Gastrointestinal disorders
Diarrhea	10/18 (55.6%)	10
Nausea	2/18 (11.1%)	2
Vomiting	2/18 (11.1%)	2
Constipation	3/18 (16.7%)	3
General disorders
Fatigue	7/18 (38.9%)	7
Pain	3/18 (16.7%)	3
Pain in extremity	4/18 (22.2%)	4
Infusion related reaction	2/18 (11.1%)	2
Non-cardiac chest pain	2/18 (11.1%)	2
Infections and infestations
Urinary tract infection	2/18 (11.1%)	2
Investigations
Alkaline phosphatase increased	6/18 (33.3%)	6
Aspartate aminotransferase increase	6/18 (33.3%)	6
Lymphocyte count decreased	7/18 (38.9%)	7
Weight loss	5/18 (27.8%)	5
White blood cell decreased	4/18 (22.2%)	4
Serum amylase increased	2/18 (11.1%)	2
Alanine aminotransferase increased	4/18 (22.2%)	4
Investigations - other	2/18 (11.1%)	2
Lipase increased	3/18 (16.7%)	3
Metabolism and nutrition disorders
Hyperglycemia	8/18 (44.4%)	8
Hypoalbuminemia	7/18 (38.9%)	7
Anorexia	4/18 (22.2%)	4
Hyponatremia	2/18 (11.1%)	2
Hypokalemia	3/18 (16.7%)	3
Hypocalcemia	5/18 (27.8%)	5
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	3/18 (16.7%)	3
Bone pain	2/18 (11.1%)	2
Nervous system disorders
Headache	2/18 (11.1%)	2
Peripheral sensory neuropathy	2/18 (11.1%)	2
Renal and urinary disorders
Hematuria	4/18 (22.2%)	4
Proteinuria	9/18 (50%)	9

Limitations/Caveats

Small sample size.

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.