Paclitaxel vs Paclitaxel + Cetuximab in Recurrent - Metastatic Head & Neck Carcinoma After Failure of a 1º Chemotherapy

Phase II, Randomized Clinical Trial to Assess the Efficacy of Paclitaxel vs Paclitaxel + Cetuximab in Subjects With Recurrent and/or Metastatic Squamous Head & Neck Carcinoma After Failure of a 1º Line Chemotherapy EXTREME Type Treatment

Treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) after progression to first line EXTREME-type treatment in patients undergoing maintenance treatment with cetuximab.

Inclusion Criteria:

1. Signed the informed consent

2. Age ≥ 18 and < 75 y

3. ECOG (Eastern Cooperative Oncology Group)performance status: 0-1

4. Life expectancy of at least 12 weeks

5. Histological or cytological confirmation of head & neck squamous cell carcinoma with localization in larynx, oropharynx, oral cavity or hypopharynx.

6. Having received at least 2 cycles of EXTREME-type chemotherapy (cisplatin or carboplatin + fluoropyrimidines + cetuximab) and being in maintenance phase with cetuximab because of having reached CR (Complete response), PR (Partial response) or SD (Stable disease) to said treatment

7. At least one measureable lesion by CT scan or MRI

8. Adequate bone marrow, liver and kidney function, according to:

   • Hb (Hemoglobin) ≥ 9.0 g/dl
   • Platelets 100,000/mm3
   • ANC (Absolute Neutrophil Count) ≥ 1,500/mm3
   • Total bilirubin ≤ 2 times the UNL
   • SGPT/ALT and SGOT/AST ≤ 3 x UNL (Upper normal limit)
   • Alkaline phosphatase ≤ 2.5 x UNL
   • Serum creatinine ≤ 1.5 times the ULN or creatinine clearance > 50 ml/min

9. Adequate nutritional status: weight loss < 20% in relationship to usual weight or albumin ≥ 35 g/l, in the last 12 w

10. Seric calcium adjusted to albumine lower or equal to 1,25 UNL.

11. Toxicity, due to previous treatment received, resolved to grade 1, before enrolment in the study

12. Women of childbearing potential should have a (-)ve pregnancy test in serum or urine,7 d before randomization. Postmenopausal women should have remained amenorrheic for at least 12 m. Furthermore, all men as well as women who participate in this study should use effective contraceptive methods beginning with the signing of the informed consent form and up to at least 6 m after the completion of the study or of the last dose, whichever occurs first

Exclusion Criteria:

1. Treatment for recurrent and/or metastatic disease other than the EXTREME- type first line (cisplatin or carboplatin + fluoropyrimidines + cetuximab)
2. Non-measurable lesion as only evidence of disease
3. Nasopharyngeal carcinoma
4. Clinical or radiographic evidence of brain metastases
5. Having history of or presenting clinically significant cardiovascular disease, such as, but not limited to, congestive heart failure, ≥ grade II of the NYHA, severe cardiac arrhythmias that require medication, or ≥ grade II peripheral vascular disease. Furthermore, those patients who have suffered myocardial infarction or unstable angina in the year prior to the onset of the study treatment or a recent onset angina in the last 3 m will also be excluded
6. History of or current presence of grade >1 peripheral neuropathy
7. History of active neurological disease
8. History of uncontrolled convulsive episode
9. Current ≥ 2 grade infection
10. Known infection by HIV or chronic infection by HBV or HBC or presence of uncontrolled and severe intercurrent infections or other severe and uncontrolled concomitant diseases
11. History of uncontrolled diabetes, uncontrolled HBP or hepatic condition.
12. History of pulmonary fibrosis, acute pulmonary damage or interstitial pneumonia
13. Any antineoplastic treatment within the 4 w prior to the randomization period
14. History of another neoplastic disease during the last 5 y, with the exception of cured "in situ" basal cell ca.skin carcinoma, "in situ" ca.bladder, "in situ" ca.cervix and "in situ" ca.prostate
15. Known allergy or suspicion of allergy or hypersensitivity to any component of cetuximab or paclitaxel
16. Previous treatment with monoclonal antibodies or other signal transduction inhibitors or EGFR-targeted treatment (Except for previous treatment with cetuximab)
17. Known drug abuse (exception Alcoholism)
18. Any important and uncontrolled medical, psychological, psychiatric, geographic or social problem that may interfere in the participation of the subject in the study and that does not allow for adequate follow-up and compliance with the protocol and evaluation of the study results
19. Women who are pregnant or in breast-feeding period
20. Use of any investigational new drug within the 4 w prior to randomization