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STA-9090(Ganetespib) in Metastatic Ocular Melanoma

Sponsor
Dana-Farber Cancer Institute (Other)
Overall Status
Completed
CT.gov ID
NCT01200238
Collaborator
Beth Israel Deaconess Medical Center (Other), Massachusetts General Hospital (Other), Brigham and Women's Hospital (Other), Synta Pharmaceuticals Corp. (Industry)
17
Enrollment
3
Locations
2
Arms
73.8
Actual Duration (Months)
5.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

STA-9090, a synthetic small molecule, demonstrates significant activity for down-regulating Heat Shock Protein 90 or Hsp90 levels. Hsp90 belongs to a class of molecular chaperone proteins known to be critical regulators of cancer cell proliferation and survival. Preclinical laboratory experiments have shown STA-9090, an Hsp90 inhibitor, could inhibit ocular melanoma cell lines. The primary objective of this trial is to obtain evaluations of STA-9090 efficacy to metastatic ocular melanoma.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Patients with metastatic ocular melanoma have a poor prognosis and very limited standard therapeutic options. The recent discoveries of GNAQ and GNA11 mutations leading to MAPK pathway activation and the over-expression of c-Met generate the hypothesis that inhibition of hsp90 client proteins will provide clinical benefit. This study tests the feasibility and efficacy of hsp90 inhibition in patients with metastatic ocular melanoma. Multiple components of the MAPK pathway (B-Raf, C-Raf, cdk4) in addition to c-Met are client proteins of hsp90 and dependent of active hsp90 for stability. Inhibition of hsp90 should lead to decreased expression of these client proteins.

Study Design

Study Type:
Interventional
Actual Enrollment :
17 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Intervention Model Description:
The original dose (Cohort A) was amended based on phase 1 data for safety. Therefore there are 2 separate arms reported.The original dose (Cohort A) was amended based on phase 1 data for safety. Therefore there are 2 separate arms reported.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of the HSP Inhibitor STA-9090 in Metastatic Ocular Melanoma
Actual Study Start Date :
Sep 17, 2010
Actual Primary Completion Date :
Oct 12, 2014
Actual Study Completion Date :
Nov 11, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: STA-9090: Cohort A

Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.

Drug: STA-9090
Other Names:
  • Ganetespib

    		•
    Experimental: STA-9090: Cohort B

    Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.

    Drug: STA-9090
    Other Names:
  • Ganetespib

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 4-month Progression Free Survival (PFS) Rate [Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Relevant for this endpoint was status at 4 months.]

      4-month PFS rate was defined as the proportion of participants alive, absent progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) and on treatment at 4 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

    2. Expression of cMET [Estimated up to 24 hours after administration of STA-9090]

      To estimate the proportion of patients with greater than 50% decrease in expression of HSP90 client protein c-MET 18-24 hours after administration of STA-9090

    Secondary Outcome Measures

    1. Objective Response Rate (ORR) [Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Median treatment duration was 1.8 months for each cohort [range: cohort A (0.9-12.5), cohort B (0.8-31.7)]. Thus, response on treatment was evaluated up to 31.7 months.]

      ORR is defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 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. CR or PR status required confirmation no earlier than 4 weeks following first documentation. 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.

    2. Disease Control Rate (DCR) [Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Median treatment duration was 1.8 months for each cohort [range: cohort A (0.9-12.5), cohort B (0.8-31.7)].Thus, response on treatment was evaluated up to 31.7 months.]

      DCR is defined as achieving stable disease (SD), partial response (P R) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 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. CR or PR status required confirmation no earlier than 4 weeks following first documentation. Progressive disease (PD) is at least a 20% increase in the sum LD of target lesions from smallest sum LD as reference or the appearance of one or more new lesions. Stable disease (SD) is neither meeting PR or PD. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. PR or better response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

    3. Progression-Free Survival (PFS) [Dz was evaluated every 8 weeks on treatment; Imaging was obtained as clinically indicated until off-study; Median (range) on-study duration (months) was cohort A: 8.7 (3.7 to 28.7) and cohort B: 4.5 (1.2 to 36.4 months). Thus, follow-up was up to 36.4m.]

      PFS based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Participants who did not experience progression were censored at date of last disease evaluation.

    4. Overall Survival (OS) [Survival follow-up occurred every 4 weeks long-term; Median (range) on-study duration (months) was cohort A: 8.7 (3.7 to 28.7) and cohort B: 4.5 (1.2 to 36.4 months).Thus, follow-up was up to 36.4m.]

      OS based on the Kaplan-Meier method is defined as the time from study entry to death or date last known alive.

    5. Grade 3-4 Treatment-Related Toxicity Rate [AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 1.8 months for each cohort [range: cohort A (0.9-12.5), cohort B (0.8-31.7)). Thus, AEs on treatment were followed up to 31.7 months.]

      All grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted to calculate the proportion of participants experiencing at least one treatment-related grade 3 or 4 AE of any type on treatment.

    Eligibility Criteria

    Criteria

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

    • Histologically confirmed stage IV ocular melanoma

    • ECOG Performance status 0, 1, or 2

    • 18 years of age or older

    • Laboratory values as indicated in the protocol

    • Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

    • Presence of metastatic disease that would be amenable to the required biopsies

    • At least one site of measurable disease as defined by at least 1cm in greatest dimension. This site must be different from the sites to be used for biopsy. No prior radiation therapy or directed ablation to the site of measurable disease

    Exclusion Criteria:

    • Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

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

    • Minor surgery within 7 days of first dose of STA-9090

    • Embolization procedure or ablation procedure to treat tumor within 4 weeks of first dose

    • Participants may not be receiving any other investigational agents

    • Poor venous access for study drug administration unless patient can use silicone based catheters

    • History of brain metastases or of leptomeningeal involvement

    • History of allergic reactions or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to STA-9090

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

    • Ventricular ejection fraction (EF) of 55% or less at baseline

    • Treatment with chronic immunosuppressants

    • Melanoma of cutaneous, mucosal or acral-lentiginous origin or of unknown primary

    • Prior treatment with HSP90 inhibitor

    • Not willing to undergo biopsy before and after treatment

    • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

    • Other medications, or severe acute/chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with the 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 participant inappropriate for entry into the study

    • Pregnant or breastfeeding women

    • Individual with a history of a different malignancy are ineligible except for circumstances outlined in the protocol

    • HIV-positive individuals on combination antiretroviral therapy

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

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

    • NYHA 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Massachusetts General Hospital Boston Massachusetts United States 02114
    2 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02115
    3 Dana-Farber Cancer Institute Boston Massachusetts United States 02115

    Sponsors and Collaborators

    • Dana-Farber Cancer Institute
    • Beth Israel Deaconess Medical Center
    • Massachusetts General Hospital
    • Brigham and Women's Hospital
    • Synta Pharmaceuticals Corp.

    Investigators

    • Principal Investigator: F. Stephen Hodi, MD, Dana-Farber Cancer Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    F. Stephen Hodi, MD, Melanoma Disease Center Director, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT01200238
    Other Study ID Numbers:
    • 10-137
    First Posted:
    Sep 13, 2010
    Last Update Posted:
    Oct 18, 2018
    Last Verified:
    Oct 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by F. Stephen Hodi, MD, Melanoma Disease Center Director, Dana-Farber Cancer Institute
    STA9090
    STA-9090
    HSP90
    Additional relevant MeSH terms:
    Melanoma

    Study Results

    Participant Flow

    Recruitment Details The first and last participants registered to cohort A on September 17, 2010 and June 6, 2011 and to cohort B on December 27, 2011 and May 12, 2014.
    Pre-assignment Detail
    Arm/Group Title STA-9090: Cohort A STA-9090: Cohort B
    Arm/Group Description Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal. Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
    Period Title: Overall Study
    STARTED 7 10
    COMPLETED 0 0
    NOT COMPLETED 7 10

    Baseline Characteristics

    Arm/Group Title STA-9090: Cohort A STA-9090: Cohort B Total
    Arm/Group Description Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal. Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal. Total of all reporting groups
    Overall Participants 7 10 17
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.3
    (6.5)
    58.5
    (18.4)
    58.0
    (14.3)
    Sex: Female, Male (Count of Participants)
    Female
    5
    71.4%
    3
    30%
    8
    47.1%
    Male
    2
    28.6%
    7
    70%
    9
    52.9%
    Region of Enrollment (Count of Participants)
    United States
    7
    100%
    10
    100%
    17
    100%

    Outcome Measures

    1. Primary Outcome
    Title 4-month Progression Free Survival (PFS) Rate
    Description 4-month PFS rate was defined as the proportion of participants alive, absent progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) and on treatment at 4 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
    Time Frame Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Relevant for this endpoint was status at 4 months.

    Outcome Measure Data

    Analysis Population Description
    The analysis dataset is comprised of all enrolled participants.
    Arm/Group Title STA-9090: Cohort A STA-9090: Cohort B
    Arm/Group Description Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal. Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
    Measure Participants 7 10
    Number (90% Confidence Interval) [proportion of participants]
    0.059
    0.8%
    0.118
    1.2%
    2. Primary Outcome
    Title Expression of cMET
    Description To estimate the proportion of patients with greater than 50% decrease in expression of HSP90 client protein c-MET 18-24 hours after administration of STA-9090
    Time Frame Estimated up to 24 hours after administration of STA-9090

    Outcome Measure Data

    Analysis Population Description
    There was a problem with the assay and therefore this endpoint was not measured.
    Arm/Group Title STA-9090: Cohort A STA-9090: Cohort B
    Arm/Group Description Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal. Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
    Measure Participants 0 0
    3. Secondary Outcome
    Title Objective Response Rate (ORR)
    Description ORR is defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 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. CR or PR status required confirmation no earlier than 4 weeks following first documentation. 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 evaluated radiologically at baseline and every 8 weeks on treatment; Median treatment duration was 1.8 months for each cohort [range: cohort A (0.9-12.5), cohort B (0.8-31.7)]. Thus, response on treatment was evaluated up to 31.7 months.

    Outcome Measure Data

    Analysis Population Description
    The analysis dataset is comprised of all enrolled participants.
    Arm/Group Title STA-9090: Cohort A STA-9090: Cohort B
    Arm/Group Description Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal. Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
    Measure Participants 7 10
    Number (90% Confidence Interval) [proportion of participants]
    0.0
    0%
    0.10
    1%
    4. Secondary Outcome
    Title Disease Control Rate (DCR)
    Description DCR is defined as achieving stable disease (SD), partial response (P R) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 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. CR or PR status required confirmation no earlier than 4 weeks following first documentation. Progressive disease (PD) is at least a 20% increase in the sum LD of target lesions from smallest sum LD as reference or the appearance of one or more new lesions. Stable disease (SD) is neither meeting PR or PD. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. PR or better 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 evaluated radiologically at baseline and every 8 weeks on treatment; Median treatment duration was 1.8 months for each cohort [range: cohort A (0.9-12.5), cohort B (0.8-31.7)].Thus, response on treatment was evaluated up to 31.7 months.

    Outcome Measure Data

    Analysis Population Description
    The analysis dataset is comprised of all enrolled participants.
    Arm/Group Title STA-9090: Cohort A STA-9090: Cohort B
    Arm/Group Description Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal. Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
    Measure Participants 7 10
    Number (90% Confidence Interval) [proportion of participants]
    0.286
    4.1%
    0.30
    3%
    5. Secondary Outcome
    Title Progression-Free Survival (PFS)
    Description PFS based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Participants who did not experience progression were censored at date of last disease evaluation.
    Time Frame Dz was evaluated every 8 weeks on treatment; Imaging was obtained as clinically indicated until off-study; Median (range) on-study duration (months) was cohort A: 8.7 (3.7 to 28.7) and cohort B: 4.5 (1.2 to 36.4 months). Thus, follow-up was up to 36.4m.

    Outcome Measure Data

    Analysis Population Description
    The analysis dataset is comprised of all enrolled participants.
    Arm/Group Title STA-9090: Cohort A STA-9090: Cohort B
    Arm/Group Description Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal. Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
    Measure Participants 7 10
    Median (90% Confidence Interval) [months]
    1.6
    1.8
    6. Secondary Outcome
    Title Overall Survival (OS)
    Description OS based on the Kaplan-Meier method is defined as the time from study entry to death or date last known alive.
    Time Frame Survival follow-up occurred every 4 weeks long-term; Median (range) on-study duration (months) was cohort A: 8.7 (3.7 to 28.7) and cohort B: 4.5 (1.2 to 36.4 months).Thus, follow-up was up to 36.4m.

    Outcome Measure Data

    Analysis Population Description
    The analysis dataset is comprised of all enrolled participants.
    Arm/Group Title STA-9090: Cohort A STA-9090: Cohort B
    Arm/Group Description Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal. Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
    Measure Participants 7 10
    Median (90% Confidence Interval) [months]
    8.5
    4.9
    7. Secondary Outcome
    Title Grade 3-4 Treatment-Related Toxicity Rate
    Description All grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted to calculate the proportion of participants experiencing at least one treatment-related grade 3 or 4 AE of any type on treatment.
    Time Frame AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 1.8 months for each cohort [range: cohort A (0.9-12.5), cohort B (0.8-31.7)). Thus, AEs on treatment were followed up to 31.7 months.

    Outcome Measure Data

    Analysis Population Description
    The analysis dataset is comprised of all enrolled participants.
    Arm/Group Title STA-9090: Cohort A STA-9090: Cohort B
    Arm/Group Description Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal. Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
    Measure Participants 7 10
    Number (90% Confidence Interval) [proportion of participants]
    0.143
    2%
    0.80
    8%

    Adverse Events

    Time Frame AE assessment was ongoing from the start of study drug and up to day 30 post-treatment; AEs were assessed for the median treatment duration of 1.8 months for each cohort and up to 12.5m in Cohort A and up to 31.7m in Cohort B and then add the 30 days post-treatment.
    Adverse Event Reporting Description Maximum grade toxicity by type was first calculated. Serious AEs were defined as grade 3 or higher events with any treatment-attribution. Other AEs were defined as grade 1 or 2 events with any treatment-attribution.
    Arm/Group Title STA-9090: Cohort A STA-9090: Cohort B
    Arm/Group Description Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal. Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
    All Cause Mortality
    STA-9090: Cohort A STA-9090: Cohort B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/7 (0%) 0/10 (0%)
    Serious Adverse Events
    STA-9090: Cohort A STA-9090: Cohort B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/7 (28.6%) 9/10 (90%)
    Gastrointestinal disorders
    Abdominal pain 0/7 (0%) 2/10 (20%)
    Diarrhea 0/7 (0%) 1/10 (10%)
    Nausea 1/7 (14.3%) 2/10 (20%)
    Vomiting 0/7 (0%) 1/10 (10%)
    General disorders
    Fatigue 1/7 (14.3%) 0/10 (0%)
    Injury, poisoning and procedural complications
    Fall 0/7 (0%) 1/10 (10%)
    Fracture 0/7 (0%) 1/10 (10%)
    Investigations
    Alanine aminotransferase increased 0/7 (0%) 2/10 (20%)
    Alkaline phosphatase increased 0/7 (0%) 4/10 (40%)
    Aspartate aminotransferase increased 0/7 (0%) 4/10 (40%)
    GGT increased 0/7 (0%) 1/10 (10%)
    Lipase increased 2/7 (28.6%) 3/10 (30%)
    Weight loss 0/7 (0%) 1/10 (10%)
    Metabolism and nutrition disorders
    Dehydration 0/7 (0%) 2/10 (20%)
    Hyperglycemia 0/7 (0%) 2/10 (20%)
    Hypophosphatemia 0/7 (0%) 2/10 (20%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/7 (14.3%) 0/10 (0%)
    Nervous system disorders
    Syncope 0/7 (0%) 1/10 (10%)
    Respiratory, thoracic and mediastinal disorders
    Hypoxia 0/7 (0%) 1/10 (10%)
    Other (Not Including Serious) Adverse Events
    STA-9090: Cohort A STA-9090: Cohort B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/7 (100%) 10/10 (100%)
    Blood and lymphatic system disorders
    Anemia 1/7 (14.3%) 3/10 (30%)
    Cardiac disorders
    Left ventricular systolic dysfunction 0/7 (0%) 1/10 (10%)
    Sinus tachycardia 0/7 (0%) 3/10 (30%)
    Ear and labyrinth disorders
    Ear and labyrinth disorders - Other, specify 0/7 (0%) 1/10 (10%)
    Eye disorders
    Blurred vision 1/7 (14.3%) 1/10 (10%)
    Eye pain 0/7 (0%) 1/10 (10%)
    Floaters 0/7 (0%) 1/10 (10%)
    Gastrointestinal disorders
    Abdominal distension 1/7 (14.3%) 1/10 (10%)
    Abdominal pain 2/7 (28.6%) 4/10 (40%)
    Anal hemorrhage 0/7 (0%) 1/10 (10%)
    Anal mucositis 0/7 (0%) 1/10 (10%)
    Bloating 0/7 (0%) 2/10 (20%)
    Constipation 2/7 (28.6%) 4/10 (40%)
    Diarrhea 5/7 (71.4%) 9/10 (90%)
    Dry mouth 0/7 (0%) 2/10 (20%)
    Duodenal hemorrhage 0/7 (0%) 2/10 (20%)
    Dyspepsia 0/7 (0%) 1/10 (10%)
    Esophagitis 0/7 (0%) 1/10 (10%)
    Gastroesophageal reflux disease 1/7 (14.3%) 0/10 (0%)
    Hemorrhoidal hemorrhage 0/7 (0%) 1/10 (10%)
    Hemorrhoids 1/7 (14.3%) 1/10 (10%)
    Ileal fistula 0/7 (0%) 1/10 (10%)
    Mucositis oral 0/7 (0%) 1/10 (10%)
    Nausea 4/7 (57.1%) 7/10 (70%)
    Oral pain 0/7 (0%) 1/10 (10%)
    Vomiting 0/7 (0%) 6/10 (60%)
    General disorders
    Chills 0/7 (0%) 1/10 (10%)
    Edema limbs 0/7 (0%) 1/10 (10%)
    Fatigue 4/7 (57.1%) 7/10 (70%)
    Fever 0/7 (0%) 2/10 (20%)
    General disorders and administration site conditions - Other, specify 0/7 (0%) 1/10 (10%)
    Infusion related reaction 1/7 (14.3%) 1/10 (10%)
    Injection site reaction 1/7 (14.3%) 0/10 (0%)
    Non-cardiac chest pain 1/7 (14.3%) 1/10 (10%)
    Pain 4/7 (57.1%) 2/10 (20%)
    Immune system disorders
    Allergic reaction 1/7 (14.3%) 0/10 (0%)
    Infections and infestations
    Abdominal infection 1/7 (14.3%) 0/10 (0%)
    Infections and infestations - Other, specify 0/7 (0%) 1/10 (10%)
    Skin infection 0/7 (0%) 2/10 (20%)
    Injury, poisoning and procedural complications
    Bruising 0/7 (0%) 1/10 (10%)
    Fall 0/7 (0%) 1/10 (10%)
    Investigations
    Activated partial thromboplastin time prolonged 0/7 (0%) 1/10 (10%)
    Alanine aminotransferase increased 1/7 (14.3%) 5/10 (50%)
    Alkaline phosphatase increased 1/7 (14.3%) 5/10 (50%)
    Aspartate aminotransferase increased 2/7 (28.6%) 5/10 (50%)
    CPK increased 0/7 (0%) 2/10 (20%)
    Creatinine increased 0/7 (0%) 1/10 (10%)
    Hemoglobin increased 0/7 (0%) 1/10 (10%)
    Lipase increased 0/7 (0%) 2/10 (20%)
    Neutrophil count decreased 0/7 (0%) 1/10 (10%)
    Platelet count decreased 0/7 (0%) 2/10 (20%)
    Serum amylase increased 2/7 (28.6%) 2/10 (20%)
    Weight loss 1/7 (14.3%) 5/10 (50%)
    White blood cell decreased 0/7 (0%) 1/10 (10%)
    Metabolism and nutrition disorders
    Anorexia 1/7 (14.3%) 9/10 (90%)
    Dehydration 1/7 (14.3%) 3/10 (30%)
    Hyperglycemia 0/7 (0%) 2/10 (20%)
    Hypoalbuminemia 1/7 (14.3%) 2/10 (20%)
    Hypocalcemia 0/7 (0%) 1/10 (10%)
    Hypoglycemia 1/7 (14.3%) 0/10 (0%)
    Hypokalemia 0/7 (0%) 1/10 (10%)
    Hypomagnesemia 0/7 (0%) 3/10 (30%)
    Hyponatremia 0/7 (0%) 4/10 (40%)
    Hypophosphatemia 2/7 (28.6%) 1/10 (10%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/7 (0%) 1/10 (10%)
    Back pain 2/7 (28.6%) 3/10 (30%)
    Chest wall pain 0/7 (0%) 1/10 (10%)
    Flank pain 1/7 (14.3%) 0/10 (0%)
    Generalized muscle weakness 1/7 (14.3%) 1/10 (10%)
    Muscle weakness left-sided 0/7 (0%) 1/10 (10%)
    Muscle weakness lower limb 1/7 (14.3%) 0/10 (0%)
    Pain in extremity 0/7 (0%) 3/10 (30%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain 0/7 (0%) 1/10 (10%)
    Nervous system disorders
    Dizziness 0/7 (0%) 2/10 (20%)
    Dysgeusia 0/7 (0%) 1/10 (10%)
    Dysphasia 0/7 (0%) 1/10 (10%)
    Headache 3/7 (42.9%) 5/10 (50%)
    Nervous system disorders - Other, specify 1/7 (14.3%) 0/10 (0%)
    Peripheral sensory neuropathy 0/7 (0%) 1/10 (10%)
    Psychiatric disorders
    Anxiety 1/7 (14.3%) 2/10 (20%)
    Depression 1/7 (14.3%) 0/10 (0%)
    Insomnia 0/7 (0%) 4/10 (40%)
    Suicidal ideation 1/7 (14.3%) 0/10 (0%)
    Renal and urinary disorders
    Urinary frequency 0/7 (0%) 1/10 (10%)
    Reproductive system and breast disorders
    Perineal pain 0/7 (0%) 1/10 (10%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/7 (14.3%) 2/10 (20%)
    Dyspnea 3/7 (42.9%) 3/10 (30%)
    Epistaxis 0/7 (0%) 1/10 (10%)
    Hiccups 0/7 (0%) 2/10 (20%)
    Hoarseness 0/7 (0%) 1/10 (10%)
    Nasal congestion 1/7 (14.3%) 0/10 (0%)
    Postnasal drip 0/7 (0%) 1/10 (10%)
    Sore throat 0/7 (0%) 2/10 (20%)
    Skin and subcutaneous tissue disorders
    Dry skin 0/7 (0%) 1/10 (10%)
    Erythema multiforme 1/7 (14.3%) 0/10 (0%)
    Hyperhidrosis 0/7 (0%) 1/10 (10%)
    Pruritus 1/7 (14.3%) 1/10 (10%)
    Rash acneiform 0/7 (0%) 1/10 (10%)
    Rash maculo-papular 3/7 (42.9%) 2/10 (20%)
    Skin and subcutaneous tissue disorders - Other, specify 0/7 (0%) 3/10 (30%)
    Surgical and medical procedures
    Surgical and medical procedures - Other, specify 0/7 (0%) 1/10 (10%)
    Vascular disorders
    Flushing 0/7 (0%) 1/10 (10%)
    Hot flashes 0/7 (0%) 2/10 (20%)
    Hypertension 0/7 (0%) 1/10 (10%)
    Hypotension 0/7 (0%) 1/10 (10%)
    Vascular disorders - Other, specify 1/7 (14.3%) 0/10 (0%)

    Limitations/Caveats

    The study was terminated early due to slow accrual and competing trials.

    More Information

    Certain Agreements

    Principal Investigators are NOT 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.

    Results Point of Contact

    Name/Title F. Stephen Hodi, MD
    Organization Dana-Farber Cancer Institute
    Phone 617.632.5053
    Email Stephen_Hodi@dfci.harvard.edu
    Responsible Party:
    F. Stephen Hodi, MD, Melanoma Disease Center Director, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT01200238
    Other Study ID Numbers:
    • 10-137
    First Posted:
    Sep 13, 2010
    Last Update Posted:
    Oct 18, 2018
    Last Verified:
    Oct 1, 2018