- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT01975519
A Phase 1B Dose-escalation and Phase 2a Study of Carotuximab (TRC105) in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma
The purpose of the phase 1b portion is to evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose pazopanib in patients with advanced soft tissue sarcoma. Up to 30 patients will be treated.
The purpose of the phase 2 portion is to estimate the PFS of patients with advanced soft tissue sarcoma by RECIST 1.1 and estimate ORR in a separate cohort of patients with angiosarcoma by RECIST 1.1. Up to 89 patients will be treated in phase 2, including two cohorts of up to 13 patients with angiosarcoma.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 2
- Fáze 1
Kontakty a umístění
Studijní místa
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Alabama
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Birmingham, Alabama, Spojené státy, 35243
- University of Alabama at Birmingham
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California
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Santa Monica, California, Spojené státy, 90403
- Sarcoma Oncology Center
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Florida
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Jacksonville, Florida, Spojené státy, 32224
- Mayo Clinic Jacksonville
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Minnesota
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Rochester, Minnesota, Spojené státy, 55905
- Mayo Clinic Rochester
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New York
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Buffalo, New York, Spojené státy, 92122
- Roswell Park Cancer Institute
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New York, New York, Spojené státy, 10029
- Mount Sinai School of Medicine-Tisch Cancer Institute
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North Carolina
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Durham, North Carolina, Spojené státy, 27710
- Duke University
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Texas
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Dallas, Texas, Spojené státy, 75230
- Mary Crowley Cancer Research Center
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Utah
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Salt Lake City, Utah, Spojené státy, 84112
- University of Utah
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Histologically confirmed unresectable soft tissue sarcoma that has progressed following treatment with chemotherapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity ( Phase 1b only)
- Histologically confirmed metastatic soft tissue sarcoma that has progressed by RECIST following treatment with anthracycline chemotherapy. Patients may have received up to four lines of systemic therapy for metastatic disease and no more than two lines of combination treatment ( Phase 2 only)
- Histologically confirmed locally advanced (e.g. unresectable) or metastatic angiosarcoma that has progressed following treatment with prior systemic therapy. Progression must be documented on or following the most recent systemic therapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity (Phase 2 angiosarcoma cohorts only)
- Measurable disease by RECIST
- Age of 12 years or older (patient must weigh ≥ 40 kg)
- ECOG performance status ≤ 1
- Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline (except alopecia or neuropathy)
- Adequate organ function.
- Willingness and ability to consent for self to participate in study
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
- Available archival tumor specimen of the soft tissue sarcoma that meets inclusion criterion #1, #2 or #3
Exclusion Criteria:
- Prior treatment with TRC105
- Prior treatment with a VEGFR TKI (including pazopanib) (Phase 2 only)
- Current treatment on another therapeutic clinical trial
- Receipt of systemic anticancer therapy, including investigational agents, within 28 days of starting study treatment.
- No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure; date of surgery (if applicable) or the anticipated need for a major surgical procedure within the next six months.
- Patients who have received wide field radiotherapy ≤ 28 days or limited field radiation for palliation < 14 days prior to cycle 1 day 1 or those patients who have not recovered adequately from side effects of such therapy
- Uncontrolled chronic hypertension
- Significant ascites or pericardial or pleural effusion
- History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
- Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6 months. Deep venous thrombosis within 6 months, unless the patient is anti-coagulated without the use of warfarin for at least 2 weeks. In this situation, low molecular weight heparin is preferred.
- Active bleeding or pathologic condition that carries a high risk of bleeding. Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible.
- Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
- Known active viral or nonviral hepatitis or cirrhosis
- History of hemorrhage or hemoptysis within 3 months of starting study treatment
- History of peptic ulcer within the past 3 months of treatment
- History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
- Receipt of a strong CYP3A4 inducer within 12 days prior to cycle 1 day 1 or a strong CYP3A4 inhibitor within 7 days prior to cycle 1 day 1.
- Pregnancy or breastfeeding. Female patients must be surgically sterile (i.e.: hysterectomy) or be postmenopausal, or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. All female patients of reproductive potential must have a negative pregnancy test (serum or urine) within 7 days prior to first dose. Male patients must be surgically sterile or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: TRC105 and Pazopanib
Weekly TRC105 in combination with standard dose pazopanib or every two week administration during cycle 1, and starting on cycle 2 day 1 and beyond, TRC105 may be administered every two weeks.
This is also in combination with standard dose pazopanib.
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Weekly TRC105 in combination with standard dose Pazopanib.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Number of Participants With Dose Limiting Toxicity (DLT)
Časové okno: 56 days
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For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0).
DLTs were defined as grade 4 neutropenia persisting for ≥ 5 days, febrile neutropenia (grade 4 neutropenia with fever > 38.5 ºC both sustained over a 24 hour period), neutropenic infection (grade ≥ 3 neutropenia with grade ≥ 3 infection), anemia ≥ grade 4, grade > 4 thrombocytopenia or grade ≥ 3 thrombocytopenia and grade ≥ 3 hemorrhage, or grade 3 or 4 nonhematologic toxicity with the following exceptions: nausea, vomiting, or diarrhea for <48 hours, asymptomatic electrolyte abnormalities that are corrected to grade 1 or better in < 72 hours, or headache lasting less than 48 hours.
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56 days
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Progression Free Survival of Patients With Advanced Soft Tissue Sarcoma (Phase 1 and 2)
Časové okno: from screening to either disease progression or death
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Number of patients with progression free survival, as defined as time from screening to either first disease progression or death from any cause per RECIST version 1.1
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from screening to either disease progression or death
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Objective Response Rate in a Cohort of Patients With Angiosarcoma
Časové okno: 1.5 years
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The best response according to RECIST 1.1 for each patient in the phase 2 angiosarcoma cohort with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type
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1.5 years
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Trough Concentrations of TRC105 (Phase 2)
Časové okno: 4, 6, 8, and 10 weeks
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Trough serum TRC105 concentrations will be measured using validated ELISA methods.
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4, 6, 8, and 10 weeks
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Number of Patients With and Without Development of Immunogenicity Antibodies (Phase 1 and 2)
Časové okno: 32 months
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Anti-product antibody concentrations will be measured using validated ELISA methods.
Anti-product antibody concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles.
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32 months
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Number of Patients With and Without Expression of Endoglin on Sarcoma Tissue (Phase 1 and 2)
Časové okno: 12 months
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Expression will be determined by immunohistochemistry for each patient who received at least one dose of TRC105
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12 months
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Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1
Časové okno: 12 months
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The best response (CR, PR, SD or PD according to RECIST 1.1) for each patient (phase 1 and phase 2) with measurable disease who received at least one dose of TRC105 study drug
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12 months
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Progression Free Survival in a Cohort of Patients With Angiosarcoma (Phase 2)
Časové okno: 26 months
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Time from screening to either first disease progression or death from any cause per RECIST version 1.1
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26 months
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Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 105SAR101
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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