STA-9090(Ganetespib) in Patients With Unresectable Stage III or Stage IV Melanoma
1 mars 2017 mis à jour par: F. Stephen Hodi, MD, Dana-Farber Cancer Institute
This Trial is an Open Label, Parallel Cohort, Phase II Study Evaluating the Efficacy of the Heat Shock Protein 90 (Hsp90) Inhibitor STA-9090 in Patients With Unresectable Stage III or Stage IV Melanoma Who Were Intolerant of, or Progressed on, Prior Tyrosine Kinase Inhibitor Treatment. Two Cohorts Will Enroll Concurrently. One Cohort Will be Composed of Patients With Melanoma Expressing a Mutation in the Protein BRAF and the Other Cohort Will be Composed of Patients With Melanoma Expressing Wild-type BRAF.
STA9090 is a drug which inactivates or blocks the work of a protein called Heat Shock Protein 90 or HSP90.
HSP90 is a protein that helps some molecules inside your cells to have the right shape.
By stopping HSP90's activity, those molecules never get to have the right structure of be functional and they are destroyed.
The investigators believe that if they stop the activity of HSP90, the rapidly dividing cells that are in your tumor(s) may slow down.
In this research study the investigators are looking to see how well STA9090 works in stopping the spread of your melanoma.
Aperçu de l'étude
Description détaillée
OBJECTIVES:
Primary
- To determine the proportion of patients alive, free of disease progression, and still taking STA-9090 at 6 months by BRAF mutant or wild type (WT) status.
Secondary
- To assess best overall response rate and six month response rate by BRAF status
- To evaluate the rates of one-year overall survival and progression-free survival by BRAF status
- To determine safety and tolerability of STA-9090 by BRAF status
Exploratory
- To compare the rates of response and of six-month PFS between BRAF status cohorts
- To explore, using peripheral blood mononuclear cells, the relationship between change in expression of hsp90 client proteins (e.g., BRAF, CRAF, AKT, CDK4, KIT) with response to therapy and progression free survival by BRAF status
- To explore the relationship in biopsied melanoma metastases between changes in expression of hsp90 client proteins (e.g., BRAF, CRAF, AKT, CDK4, KIT) with response to therapy and progression-free survival
- To explore response rate and 6 month progression free survival, in subset of patients with melanoma expressing a mutation in KIT
Type d'étude
Interventionnel
Inscription (Réel)
3
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Massachusetts
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Boston, Massachusetts, États-Unis, 02215
- Dana-Farber Cancer Institute
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
- Histologically confirmed unresectable stage III or stage IV melanoma
- Treatment of unresectable stage III or stage IV melanoma with a tyrosine kinase inhibitor within prior 4 months. Sorafenib for purposes of eligibility will not be considered acceptable prior therapy
- Sufficient tumor available to determine if expresses wild-type or mutated BRAF if result not already known. The presence or absence of BRAF mutation needs to be determined at BWH, MGH, BIDMC, by Drs. Christopher Corless and Michael Heinrich at Cancer Pathology Shared Resource Oregon Health & Science University, or in context of eligibility assessment after signing consent to a previous clinical trial
- Sufficient tumor available to determine if expresses a mutation KIT
- Agreement to allow tumor to be evaluated for mutations in KIT and BRAF
- ECOG performance status ≤ 1
- Life expectancy of ≥ 6 months
- Age ≥ 18 years
- WBC ≥ 3 x 103/ul
- ANC ≥ 1,500/ul
- Platelets ≥ 100 x 103/ul
- Hemoglobin ≥ 9 gm/dl
- Serum creatinine ≤ 1.5 x ULN
- Calculated creatinine clearance ≥ 60 mL/min
- AST ≤ 2.5 x ULN; -OR- AST ≤ 5 x ULN in the presence of known liver metastases
- ALT ≤ 2.5 x ULN; -OR- ALT ≤ 5 x ULN in the presence of known liver metastases
- Total bilirubin ≤ 1.5 x ULN
- Potassium within normal range or correctable with supplements
- Magnesium within normal range or correctable with supplements
- Corrected serum calcium within normal range, or correctable with supplements
- Not pregnant or breastfeeding. Female subjects of childbearing age must have a negative serumpregnancy test at study entry
- Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation and for 6 months following last study drug administration
- Agreement to provide blood samples for pharmacodynamic studies utilizing Peripheral Blood Mononuclear Cells (PMBCs) as outlined in protocol
- At least one site of measurable disease as defined by at least 1 cm 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 measureable disease
- Able to understand and willing to sign a written informed consent document
- Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
- No chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study entry
- No radiotherapy within 4 weeks prior to study entry
- Subject has recovered from adverse events due to agents administered more than 4 weeks earlier
- No tyrosine kinase inhibitor within 14 days prior to study entry
- No major surgery within 4 weeks prior to first dose of STA-9090
- No minor surgery within 7 days of first dose of STA-9090
- No history of or current coronary artery disease, myocardial infarction, angina pectoris, angioplasty
- or coronary bypass surgery
- No current treatment with the following antiarrythmic drugs: flecainide, moricizine or propafenone
- No NYHA class II/III/IV congestive heart failure with a history of dyspnea, orthopnea, or edema that requires current treatment with angiotensin convering enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, or diuretics
- No current or prior radiation to the left hemithorax
- No embolization procedure or ablation procedure to treat tumor within 4 weeks of first dose of STA- 9090
- Not receiving any other investigational agents
- No poor venous access for study drug administration unless subject can use silicone based catheters
- No history of brain metastases or of leptomeningeal involvement
- No history of severe allergic reactions or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to STA-9090 (e.g. olyethylene glycol [PEG] 300 or Polysorbate 80)
- Baseline QTc ≤ 470 msec
- No previous history of QT prolongation while taking other medications
- Ventricular ejection fraction (EF) > 55%
- No treatment with chronic immunosuppressants
- No melanoma of ocular primary
- No prior treatment with hsp90 inhibitor
- No uncontrolled intercurrent illness including, but not limited to ongoing or active infection, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- No other medications, or severe acute/chronic medical of 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 subject inappropriate for entry into the study
- No history of a different malignancy except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
- No HIV-positive subject on combination antiretroviral therapy
- No more than 3 prior systemic therapies for unresectable stage III or stage IV melanoma
- No concomitant use of medications associated with a high incidence of QT prolongation as outlined
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: STA-9090 Cohort A
Patients enrolled into two possible cohorts based on tumor expression of BRAF: Cohort A - BRAF mutant disease or Cohort B - BRAF wild type.
Cohort A patients received STA-9090 200 mg/m2 once weekly (d1, 8, 15 of 28 day cycle).
Patients were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
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Autres noms:
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Expérimental: STA-9090 Cohort B
Patients enrolled into two possible cohorts based on tumor expression of BRAF: Cohort A - BRAF mutant disease or Cohort B - BRAF wild type.
Cohort B patients received STA-9090 150 mg/m2 twice weekly (d1, 4, 8, 11, 15, 18 of 28 day cycle).
Patients were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
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Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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6-month Progression-Free Survival Rate
Délai: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until evidence of disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 6 months.
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6-month progression-free survival rate was defined as the proportion of patients absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 6 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 or the appearance of one or more new lesions.
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.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until evidence of disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 6 months.
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Best Overall Response
Délai: Disease was evaluated radiologically at baseline and every 8 weeks on treatment. Median (range) treatment duration was 1 cycle/4 weeks (1-2 cycles; 4-8 weeks).
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Best overall response (BOR) on treatment was based on RECIST 1.0 criteria.
For target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (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 confirmation required within 4 weeks.
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.
CR is disappearance of all non-target lesions.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment. Median (range) treatment duration was 1 cycle/4 weeks (1-2 cycles; 4-8 weeks).
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Overall Survival
Délai: Patients were followed every 4 weeks for survival until death, lost to follow-up or study closure (approximately 6 months after the last patient ended treatment). In this study cohort, patients were followed up to 13 weeks.
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Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
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Patients were followed every 4 weeks for survival until death, lost to follow-up or study closure (approximately 6 months after the last patient ended treatment). In this study cohort, patients were followed up to 13 weeks.
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: F. Stephen Hodi, M.D., Dana-Farber Cancer Institute
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 septembre 2011
Achèvement primaire (Réel)
1 septembre 2012
Achèvement de l'étude (Réel)
1 septembre 2012
Dates d'inscription aux études
Première soumission
29 avril 2011
Première soumission répondant aux critères de contrôle qualité
8 mars 2012
Première publication (Estimation)
13 mars 2012
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
12 avril 2017
Dernière mise à jour soumise répondant aux critères de contrôle qualité
1 mars 2017
Dernière vérification
1 janvier 2017
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 11-039
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Non
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Oui
Étudie un produit d'appareil réglementé par la FDA américaine
Non
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