Phase II trial of carboplatin/paclitaxel and cetuximab, followed by carboplatin/paclitaxel/cetuximab and erlotinib, with correlative studies in patients with metastatic or recurrent squamous cell carcinoma of the head and neck.

Summary

This study will be an open-label phase ii study conducted at Fox Chase Cancer Center and other sites. The study will enroll 43 patients with metastatic or recurrent squamous cell carcinoma of the head and neck, who have not previously received systemic therapy for this stage of their cancer. Patients will have tumor assessment and tumor biopsy, followed by treatment with carboplatin/paclitaxel combination chemotherapy given with cetuximab. Following the first 21day cycle, tumor assessment and biopsy will be repeated, followed by resumption of therapy with the addition of oral erlotinib followed by a repeat biopsy. Results will be compared to historical controls, as well as each patient serving as a self-control between cycles 1 and 2.

Pre-treatment biopsy at the descretion of the treating physician
anti-emetics
Carboplatin x auC[?] 2 iV q week
Paclitaxel x 80 mg/m2 iV q week
Cetuximab -250mg/m2 iV q week
Patients will complete one 21-day cycle of this treatment, and undergo repeat biopsy.
The identical therapy will be resumed, with the addition of erlotinib (Tarceva) 150mg daily.
Patients will complete the second 21-day cycle of this treatment, and undergo a biopsy.
Patients may continue on treatment until progression of disease or intolerable toxicity.
Biopsies are optional and will be conducted at the discretion of the treating physician.

Participant Eligibility

Patients must fulfill all of the following criteria to be eligible for study entry:
1. Histologically confirmed squamous cell carcinoma of the head and neck that is metastatic or recurrent.
2. No prior systemic therapy for metastatic/recurrent disease.
3. ECOG performance status 0-1.
4. Prior chemotherapy in the induction, organ preservation or adjuvant setting is permitted if it was completed more than 4 months prior to enrollment on the current study.
5. Prior cetuximab is permitted if it was given for no more than 9 doses in combination with radiation therapy or chemoradiation therapy for initial treatment of locally advanced disease.
6. No prior erlotinib, gefitinib or lapatinib therapy is permitted; nor is prior exposure to any investigational EGFR or panErbB reversible or irreversible inhibitor or any prior panitumumab or investigational EGFR-directed monoclonal antibody permitted.
7. Age > 18.
8. Hemoglobin > 9.0 G/dl.
9. ANC > 1500 cells/mcl.
10. Creatinine (Cr) < 1.8.
11. Total bilirubin < the institution[Single Quote]s upper limits of normal (ULN), AST and ALT < 2 X ULN.
12. No chronic active viral infection.
13. No chronic diarrheal condition.
14. Females should not be pregnant or breast feeding because chemotherapy may be harmful to the fetus or the nursing infant. Also, the effects of erlotinib and cetuximab on the developing human fetus are unknown.
15. All females of childbearing potential must have a blood test or urine study < 2 weeks prior to enrollment to rule out pregnancy.
16. Women of childbearing potential and sexually active males must use an accepted and effective method of contraception while on treatment and for three months after the completion of treatment.
17. Patients must have measurable disease based on RECIST v 1.1 (see Sec. 5.0). Baseline measurements and evaluations must be obtained within < 4 weeks of enrollment. All areas of disease should be recorded and mapped out in order to assess response and uniformity of response to therapy. Disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma following radiation therapy. Persistent disease without clear-cut progression after radiotherapy can be considered measurable if biopsy-proven at least 8 weeks after completion of radiation therapy.
18. Patients with a prior history of squamous cell or basal carcinoma of the skin or in situ cervical cancer must have been curatively treated. Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 3 years post diagnosis.
19. No current peripheral neuropathy > grade 2 at time of randomization.
20. Patients must not have any co-existing condition that would preclude full compliance with the study.
21. Known HIV positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with erlotinib.
22. Patients must have no history of allergic reaction to murine proteins.
23 Ability to understand and the willingness to sign a written informed consent.
24. Patients must not be receiving other investigational anti-cancer therapy.
25. Patients with known brain metastases are not eligible.