Erlotinib and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney, Colorectal, Head and Neck, Pancreatic, or Non-Small Cell Lung Cancer
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip
About this trial
This is an interventional treatment trial for Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Eligibility Criteria
Inclusion Criteria: One of the following histologically confirmed diagnoses: Renal cell cancer Clear cell histology Metastatic or unresectable disease AND meets 1 of the following criteria: Recurrent disease Refractory to interleukin-2 (IL-2)- or interferon-based therapy Previously untreated AND not a candidate for IL-2-based therapy Colorectal, head and neck, pancreatic, or non-small cell lung cancer Metastatic or unresectable disease Progression after prior standard treatment No evidence of CNS disease, including the following (part 2 only): Primary brain tumor Brain metastases Paraffin embedded tumor blocks available Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% More than 12 weeks Absolute neutrophil count ≥ 1,500 mm^3 Platelet count ≥ 100,000 mm^3 Bilirubin ≤ 1.5 mg/dL AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastasis is present) PTT and INR ≤ 1.5, unless receiving full-dose warfarin (part 2 only) Creatinine ≤ 1.5 times ULN Creatinine clearance ≥ 60 mL/min Calcium < 10 mg/dL (hypocalcemic agents allowed) No proteinuria* Protein < 1 g on 24-hour urine collection* No unstable angina pectoris No cardiac arrhythmia No symptomatic congestive heart failure None of the following are allowed for part 2: Myocardial infarction within the past 6 months New York Heart Association class II-IV heart disease Serious cardiac arrhythmia requiring medication Peripheral vascular disease ≥ grade II Recent history of cerebrovascular accident Uncontrolled hypertension (blood pressure ≥ 150/85 mm Hg despite medication) Other clinically significant cardiovascular disease No gastrointestinal (GI) tract disease resulting in an inability to take oral medication No GI tract disease resulting in a requirement for IV alimentation No active peptic ulcer disease No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (part 2 only) No ongoing or active infection No active infection requiring parenteral antibiotics (part 2 only) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 months after study treatment No significant traumatic injury within the past 28 days (part 2 only) No history of abnormalities of the cornea (e.g., dry eye syndrome, Sjögren's syndrome, or congenital abnormality [e.g., Fuch's dystrophy]) No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the breast or cervix No psychiatric illness or social situation that would preclude study compliance No serious or non-healing wound ulcer or bone fracture (part 2 only) No other uncontrolled illness See Disease Characteristics More than 4 weeks since prior immunotherapy No prior cetuximab No prior bevacizumab Concurrent epoetin alfa or darbepoetin alfa allowed More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) More than 4 weeks since prior radiotherapy No prior surgical procedures affecting absorption Prior nephrectomy or resection of metastatic lesions allowed provided patient has fully recovered More than 7 days since prior core biopsy* More than 28 days since prior major surgery or open biopsy* No concurrent major surgery* Recovered from all prior therapy No prior erlotinib Concurrent bisphosphonates allowed Concurrent full-dose anticoagulants allowed provided the following criteria are met (part 2 only): In-range INR (usually between 2 and 3) AND on a stable dose of warfarin or low molecular weight heparin No active bleeding No pathological conditions that carry a high risk of bleeding (e.g., tumor involving major vessels or varices) No other concurrent investigational agents No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent anticancer therapy
Sites / Locations
- Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
Arms of the Study
Arm 1
Experimental
Treatment (erlotinib hydrochloride, cetuximab, bevacizumab)
Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15. Cohorts of 3-6 patients receive escalating doses of bevacizumab until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. In both groups, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.