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- Klinische proef NCT01721525
Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
Phase I Study of Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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New Jersey
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Basking Ridge, New Jersey, Verenigde Staten, 07939
- Memorial Sloan Kettering Cancer Center at Basking Ridge
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New York
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New York, New York, Verenigde Staten, 10065
- Memorial Sloan Kettering Cancer Center
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Department of Pathology at MSKCC confirmation of diagnosis of oropharynx squamous cell cancer, stage IVA/IVB, that is HPV associated.
Evidence of HPV can be p16 immunohistochemistry and/or HPV in situ hybridization positive test result on tumor tissue, either at MSKCC or other CLIA-approved lab.
- Age ≥ 18 years of age
- Karnofsky Performance Status ≥ 80
- Adequate organ function, as follows:
Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 X 109/L, platelets ≥ 160 X 109/L, hemoglobin ≥ 12 g/dL Hepatic: total bilirubin within normal limits (≤ 1.0 mg/dL); alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 X ULN (upper limit of normal) Renal: Serum creatinine ≤ 1.3 mg/dL. Patients with serum creatinine > 1.3 mg/dL may be eligible if creatinine clearance (CrCl) ≥ 55 mL/min based on the standard Cockroft and Gault formula.
- Patients of childbearing potential must have a negative serum pregnancy test within 14 days of treatment. Patients must agree to use a reliable method of birth control during and for 6 months following the last dose of study drug.
- Ability to swallow oral medication.
- Expansion Cohort only: At least one unstained slide from pre-treatment diagnostic biopsy or fine needle aspirate must be available for correlative immunohistochemistry study.
Exclusion Criteria:
- Prior chemotherapy or radiation for tonsillar or base of tongue squamous cell cancer
- History of hemolytic anemia or thalassemia
- Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment.
- Current therapeutic anticoagulation with Coumadin (warfarin)
- Current or prior treatment with ribavirin
- Known active Hepatitis B or C
- Any prior documented history of transient ischemic attack (TIA) or cerebrovascular accident (CVA)
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- Clinically significant peripheral vascular disease
- Inability to discontinue any of the following potent P-gp inhibitors (cyclosporine, erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital salt with quinidine, ritonavir, valspodar, verapamil) or inducers (St John's wort, rifampicin).
- Known pre-existing interstitial lung disease.
- Presence of poorly controlled gastrointestinal disorders that could affect the absorption of the trial drug (e.g. Crohn's disease, ulcerative colitis, malabsorption, or CTC grade ≥2 diarrhea of any etiology) based on treating physician assessment.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: afatinib, ribavirin, and weekly carboplatin/paclitaxel
This will be a single institution phase I study with an expansion cohort.
Up to 2 dose levels of daily afatinib will be studied: 30 mg/day and 40 mg/day.
The doses of ribavirin, carboplatin, and paclitaxel are fixed.
A standard 3 + 3 phase I dose escalation design will be used.
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Patients will receive oral daily afatinib (days 1 - 21, per dose escalation scheme) plus daily oral ribavirin (days 1- 21) and paclitaxel (80 mg/m2 intravenously, days 1 and 8) + carboplatin (AUC 1.5 intravenously, days 1 and 8) of a 21-day cycle.
Ribavirin will be administered according to standard weight-based dosing for this drug (1).
Subjects ≤75 kg receive Ribavirin 400 mg PO qAM and 600 mg PO qPM (= 1000 mg/day).
Subjects > 75 kg receive Ribavirin 600 mg PO BID (=1200 mg/day).
During the Dose Escalation portion of the study (Part 1), research bloodwork for pharmacokinetics is performed on days 1 and 8 of Cycle 1 only.
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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maximum tolerated dose (For Dose Escalation Portion of the study)
Tijdsspanne: 1 year
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of daily oral afatinib administered with standard daily weight based ribavirin and intravenous carboplatin and paclitaxel, Up to 2 dose levels of daily afatinib will be studied: 30 mg/day and 40 mg/day.
The doses of ribavirin, carboplatin, and paclitaxel are fixed.
A standard 3 + 3 phase I dose escalation design will be used.
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1 year
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expression of PTPN13 (For Expansion Cohort only)
Tijdsspanne: 1 year
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To determine if a two week run-in with afatinib and ribavirin results in increased expression of PTPN13, as determined by IHC in pre and post treatment biopsies.
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1 year
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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safety and tolerability (toxicity)
Tijdsspanne: 1 year
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Adverse events (AEs) will be assessed according to NCI common toxicity criteria (CTC) version 4.0.
Dose Limiting Toxicity (DLT) include all toxicities of grade 3 or higher felt to be possibly, probably, or definitely related to study drug.
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1 year
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objective response rate
Tijdsspanne: 1 year
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Response and progression will be evaluated in this study using modified international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) (51).
Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
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1 year
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pharmacokinetics
Tijdsspanne: 1 year
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PK measurements will be collected from patients in the dose excalation cohort during the first cycle of therapy.
The area under the curve (AUC0→∞), half-life (t½), and maximum concentration (Cmax) for afatinib will be determined by noncompartmental analysis.
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1 year
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Medewerkers en onderzoekers
Publicaties en nuttige links
Nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Neoplasmata per histologisch type
- Neoplasmata
- Carcinoom
- Neoplasmata, glandulair en epitheel
- Carcinoom, plaveiselcel
- Neoplasmata, plaveiselcel
- Moleculaire mechanismen van farmacologische werking
- Anti-infectieuze middelen
- Antivirale middelen
- Enzymremmers
- Antimetabolieten
- Antineoplastische middelen
- Tubuline-modulatoren
- Antimitotische middelen
- Mitose modulatoren
- Antineoplastische middelen, fytogeen
- Proteïnekinaseremmers
- Carboplatine
- Paclitaxel
- Ribavirine
- Afatinib
Andere studie-ID-nummers
- 12-150
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