STA-9090(Ganetespib) in Patients With Unresectable Stage III or Stage IV Melanoma
1. mars 2017 oppdatert av: 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.
Studieoversikt
Detaljert beskrivelse
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
Studietype
Intervensjonell
Registrering (Faktiske)
3
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Massachusetts
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Boston, Massachusetts, Forente stater, 02215
- Dana-Farber Cancer Institute
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
- 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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: 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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Andre navn:
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Eksperimentell: 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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Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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6-month Progression-Free Survival Rate
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Best Overall Response
Tidsramme: 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
Tidsramme: 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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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: F. Stephen Hodi, M.D., Dana-Farber Cancer Institute
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. september 2011
Primær fullføring (Faktiske)
1. september 2012
Studiet fullført (Faktiske)
1. september 2012
Datoer for studieregistrering
Først innsendt
29. april 2011
Først innsendt som oppfylte QC-kriteriene
8. mars 2012
Først lagt ut (Anslag)
13. mars 2012
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
12. april 2017
Siste oppdatering sendt inn som oppfylte QC-kriteriene
1. mars 2017
Sist bekreftet
1. januar 2017
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 11-039
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Nei
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Ja
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
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