Clinical trial NCT01721525: Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
Official title: Phase I Study of Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Head and Neck Cancer
Squamous Cell Cancer
Keywords: BIBW2992 (AFATINIB)
CARBOPLATIN
RIBAVIRIN-ICN (VIRAZOLE)
TAXOL (PACLITAXEL)
OROPHARYNX
HPV associated
12-150
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
name: Boehringer Ingelheim
First posted: 2012-11-04
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study seeks to develop a new induction chemotherapy regimen which is a combination of two pill drugs taken by mouth and two drugs given by vein. This is a phase I study, which means that the primary goal is to establish the recommended dose of an investigational drug when added to chemotherapy. The researchers wish to evaluate the effects, good and bad, of the investigational drug.


Eligibility criteria: 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.

Primary outcomes:
measure: maximum tolerated dose (For Dose Escalation Portion of the study)
timeFrame: 1 year
measure: expression of PTPN13 (For Expansion Cohort only)
timeFrame: 1 year
Secondary outcomes:
measure: safety and tolerability (toxicity)
timeFrame: 1 year
measure: objective response rate
timeFrame: 1 year
measure: pharmacokinetics
timeFrame: 1 year
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center at Basking Ridge
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: David Pfister, MD
role: PRINCIPAL_INVESTIGATOR
References: