Clinical trial NCT00405405: Phase I of Biologics and Chemoradiation Therapy for Advanced Head and Neck Cancer
Official title: A Phase I Study of the Combination of Chemoradiotherapy With Biologic Therapy for Advanced Head and Neck Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Head and Neck Cancer
Parotid Gland Cancer
Thyroid Gland Cancer
Melanoma
Stage IV Head and Neck Cancer
Keywords: Head and neck cancer
Parotid gland cancer
thyroid gland cancer
melanoma
Chemoradiotherapy
bevacizumab
erlotinib
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2006-11-30
Enrollment: 13
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: To determine a safe and effective doses of two biologic drugs, erlotinib and bevacizumab when used with chemotherapy and radiation therapy in advanced head and neck cancer

Detailed description: Locally advanced non-operative, Stage IV head and neck cancer has at best a guarded prognosis. Improvements in outcome have been achieved via the combination of chemotherapy and radiotherapy. Concurrent chemoradiotherapy is needed to optimize results, although recent data suggest a benefit from induction therapy as well. Nonetheless, despite high remission rates, most of these patients will suffer local-regional and/or distant recurrence from their disease.

The proposed study will build upon the framework of chemoradiotherapy (induction plus concurrent) via the addition of a double biologic therapy. Specifically, the combination of bevacizumab and erlotinib will be used, as has been studied in other types of cancer.

Eligibility criteria: Inclusion Criteria:

* Locally advanced Carcinoma (epithelial malignancy) of the head and neck. This may include non-squamous carcinomas (e.g. parotid, thyroid, melanoma) in which a large portion of mucosa of the oral cavity and/or laryngopharynx is expected to be irradiated.
* Stage IV disease (T4Nany or TanyN2-3).
* "Oligometastatic" disease is allowable if it is asymptomatic.
* Measurable disease is not required; patients who have had surgical resection are eligible provided that it is felt that the likelihood of cure with conventional postoperative therapy is \<40% and provided that there will be at least 28 days from the date of surgery to the start of study therapy.
* Performance status 0-1.
* Creatinine \< or = 1.5 mg/dl.
* ANC \> or = 1,800 cells/mm3.
* Platelets \> or = 150,000 cells/mm3.
* Hemoglobin \> or = 10 g/dl (transfusion is acceptable if needed).
* SGOT and/or SGPT \< or = 2.5 times the upper institutional limit of normal.
* INR \< or = 2.0.
* Age \> or = 18 (informed consent).

Exclusion Criteria:

* Current, recent (within 4 weeks of the Day 1, the first infusion of drug in this study) or planned participation in an experimental drug study other than this one.
* Poorly controlled blood pressure, defined as systolic bp \> 150 and/or diastolic bp \> 100 despite medication.
* Unstable angina.
* NY Heart Association (NYHA) Grade II or greater congestive heart failure.
* History of myocardial infarction or stroke within 6 months.
* Clinically significant peripheral vascular disease.
* Evidence of bleeding diathesis or coagulopathy.
* Presence of brain or spinal cord metastases.
* Major surgical procedure(s), open biopsy or significant traumatic injury within 28 days prior to Day 1 (1st day of study treatment) and/or anticipation of need for major surgical procedure during the course of the study.
* Urine protein: Creatinine ratio \> or = 1.0 at screening.\*
* Carotid artery exposure or other signs of impending carotid artery hemorrhage.
* History of abdominal fistula and/or gastrointestinal abdominal abscess within 6 months prior to enrollment.
* Serious, non-healing wound, ulcer, or bone fracture.
* Prior irradiation that would result in radiotherapy field "overlap."
* Requirement for high dose oral anticoagulation (i.e., goal INR \> 2.0). "Mini-dose" anticoagulation as may be used to assist in patency of central venous lines is acceptable. Subcutaneous Low-molecular weight heparin is allowable.
* No known allergies to any of the drug therapies being used in this protocol.
* No pregnancy, lactation or inability to use medically acceptable birth control if of childbearing potential.

Primary outcomes:
measure: Bevacizumab and Erlotinib Combined with Chemoradiotherapy for the Treatment of Advanced Head and Neck Cancer
timeFrame: Day 36
Secondary outcomes:
measure: Determination of Dose Limiting Toxicity (DTL)
timeFrame: 30 days
measure: Complete Remission Rate
timeFrame: 6 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Pramila Rani Anne, MD
role: PRINCIPAL_INVESTIGATOR
References: