Study of Tremelimumab Alone or Combined With Olaparib for Patients With Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)
An Open Label Dose Escalation/Expansion Study of Tremelimumab Alone or Combined With Olaparib for Recurrent or Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Descrizione dettagliata
Tipo di studio
Tipo di studio
Iscrizione (Effettivo)
Iscrizione
Fase
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
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Maryland
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Baltimore, Maryland, Stati Uniti, 21231
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Signed informed consent form
- Age ≥ 18 years
- Recurrent or persistent EOC (epithelial ovarian, fallopian tube or primary peritoneal carcinoma)
- Have archival tissue or willingness to undergo a tumor biopsy
- Have measurable disease
- Have had one prior taxane-platinum-based chemotherapeutic regimen
- Have had a treatment-free interval following platinum-based therapy of less than 12 months, have progressed during platinum-based therapy, or had persistent disease after a platinum-based regimen
- Have received hormonal therapy
- ECOG Performance Status of 0 to 1
- Ability to take oral medications
- HIV, HTLV-1, HBV, and HCV negative
- Adequate organ and bone marrow function as defined by study-specified laboratory tests
- Normal blood coagulation parameters
- Life expectancy greater than 16 weeks
- Must use acceptable form of birth control through the study and for 28 days after final dose of study drug
- Willing and able to comply with study procedures
Exclusion Criteria:
- Prior therapy with an anti-CTLA-4 antibody or PARP inhibitor
- Active infection requiring antibiotics
- Active autoimmune disease
- Active and uncontrolled intercurrent illness
- History of other cancers within the past 5 years
- Systemically active steroid use
- Receiving systemic chemotherapy or radiotherapy within 4 weeks prior to the first dose of study drug
- Use of ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir
- Requirement for chronic parenteral hydration/nutrition
- Vaccination with live attenuated vaccine within 1 month prior to first dose of study drug
- Patients with untreated brain metastases, treated brain metastases that are not stable, leptomeningeal disease, or seizures uncontrolled with standard medical therapy
- Patients with myelodysplastic syndrome/acute myeloid leukaemia
- History of diverticulitis
- History of bleeding disorder or diathesis.
- Serious or nonhealing wound, ulcer, bone fracture, or osteonecrosis of the jaw
- Major surgical procedure within 28 days of study enrollment, or anticipated while on study.
- Pregnant or breast feeding woman
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Numero di armi
Armi e interventi
Gruppo di partecipanti / ArmGruppo di partecipanti / Arm |
Intervento / TrattamentoIntervento / Trattamento |
|---|---|
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Sperimentale: Arm A: Tremelimumab Alone
25 patients will receive tremelimumab alone at 10 mg/kg IV every 4 weeks for 7 doses then every 12 weeks until disease progression.
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Sperimentale: Arm B1: DESE Tremelimumab and Olaparib
18 patients will receive tremelimumab (3 or 10 mg/kg IV) every 4 weeks for 7 doses then every 12 weeks and olaparib (150 or 300 mg orally twice a day) until disease progression.
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Altri nomi:
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Sperimentale: Arm B2: Tremelimumab and Olaparib
25 patients will receive tremelimumab (every 4 weeks for 7 doses then every 12 weeks) and olaparib (daily) until disease progression.
Dose of tremelimumab and olaparib will be determined during the DESE (Arm B1).
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Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Adverse events as a measure of the safety and tolerability profile of tremelimumab in combination with olaparib
Lasso di tempo: 4 years
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Number of participants experiencing study drug-related dose limiting toxicities (DLTs).
Dose escalation (phase I) portion of the trial only.
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4 years
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Fold change from baseline in the ratio of peripheral CD4+ICOShi T cells and Regulatory T cells
Lasso di tempo: 4 years
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Dose escalation (phase I) portion of the trial only.
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4 years
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Maximum Tolerated Dose (MTD) of tremelimumab combined with olaparib
Lasso di tempo: 4 years
|
Dose escalation (phase I) portion of the trial only.
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4 years
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Misure di risultato secondarie
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Sopravvivenza globale (OS)
Lasso di tempo: 4 anni
|
L'OS sarà misurato dalla data della prima dose fino alla morte o alla fine del follow-up (l'OS sarà censurata alla data in cui il soggetto era noto per l'ultima volta essere vivo per i soggetti senza documentazione di morte al momento dell'analisi).
Stima basata sulla curva di Kaplan-Meier.
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4 anni
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Progression Free Survival (PFS) Rate at 6 months by RECIST
Lasso di tempo: 6 months
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PFS rate is defined as the percentage of patients with disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria) or death due to any cause at 6 months.
Per RECIST 1.1 criteria, Complete Response (CR) = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
Estimation based on the Kaplan-Meier curve.
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6 months
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Progression Free Survival (PFS) Rate at 6 months by irRECIST
Lasso di tempo: 6 months
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PFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRECIST criteria) or death due to any cause at 6 months.
Per irRECIST criteria, irCR = disappearance of all lesions, irPR is =>30% decrease in tumor burden, irPD is >20% increase in tumor burden compared with nadir, irSD is <30% decrease in tumor burden compared with baseline cannot be established nor <20% increase compared with nadir.
Estimation based on the Kaplan-Meier curve.
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6 months
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Objective Response Rate (ORR) by RECIST
Lasso di tempo: 4 years
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Objective Response Rate (ORR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.
Per RECIST 1.1 criteria, CR = disappearance of all target lesions and PR is =>30% decrease in sum of diameters of target lesions.
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4 years
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Objective Response Rate (ORR) by irRECIST
Lasso di tempo: 4 years
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Objective Response Rate (irORR) is defined as the percentage of patients achieving a complete response (irCR) or partial response (irPR) based on irRECIST criteria.
Per irRECIST criteria, irCR = disappearance of all lesions and irPR is =>30% decrease in tumor burden.
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4 years
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Duration of Response by RECIST
Lasso di tempo: 4 years
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Number of months from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented.
Per RECIST 1.1 criteria, CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, and PD is >20% increase in sum of diameters of target lesions.
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4 years
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Duration of Response by irRECIST
Lasso di tempo: 4 years
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Number of months from the start date of irPR or irCR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented.
Per irRECIST criteria, irCR = disappearance of all lesions, irPR is =>30% decrease in tumor burden, and irPD is is >20% increase in tumor burden compared with nadir.
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4 years
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Disease Control Rate (DCR)
Lasso di tempo: 4 years
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DCR is defined as the number of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria at any time during the study.
CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, PD is >20% increase in sum of diameters of target lesions, SD is <30% decrease or <20% increase in sum of diameters of target lesions.
Estimation based on the Kaplan-Meier curve.
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4 years
|
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Progression-Free Survival (PFS)
Lasso di tempo: 4 years
|
PFS is defined as the number of patients with disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause.
Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
Estimation based on the Kaplan-Meier curve.
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4 years
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Collaboratori e investigatori
Sponsor
Sponsor
Collaboratori
Collaboratori
Investigatori
Investigatori
- Investigatore principale: Stéphanie Gaillard, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Inizio studio
Completamento primario (Effettivo)
Completamento primario
Completamento dello studio (Effettivo)
Completamento dello studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- J15113
- IRB00064379 (Altro identificatore: JHM IRB)
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