Study of the Combination of Panitumumab With Paclitaxel as First-line Treatment of Subjects With Head and Neck Cancer

The clinical hypothesis of this study is that the first-line treatment with the combination of panitumumab and paclitaxel will provide benefit for patients with metastatic or current Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Panitumumab, a fully human IgG2 anti-EGFR monoclonal antibody, has shown activity in preclinical models of SCCHN, and promising activity in refractory SCCHN patients in a phase I clinical trial. Recently, the investigators also reported encouraging outcomes of anti-EGFR-paclitaxel combination in a phase II study. On the basis of this background, a phase II clinical trial (VECTITAX study) was designed with the objective of evaluating the activity and safety profile of panitumumab in combination with paclitaxel in patients with recurrent or metastatic SCCHN.

The VECTITAX study was a single arm, open label, multicenter, phase II clinical trial. To be included patients had to have histologically or cytologically confirmed SCCHN. The current situation had to be recurrent or metastatic, deemed to be untreatable by surgery or radiotherapy. No previous systemic antineoplastic therapy for the recurrent/metastatic disease may have been administered. However, previous chemotherapy was allowed as a part of a multimodality radical treatment if completed \>24 weeks before study entry.

Primary endpoint was confirmed objective response rate (ORR) according to RECIST 1.1 criteria in the intention-to-treat population (ITT). Tumor assessments were planned to be performed every two months. Response confirmation was to be assessed not before 4 weeks after a partial or complete response, or before 6 weeks after a stable disease. Secondary endpoints were disease control rate, time to response, duration of response, progression-free survival (PFS), OS, safety profile and QoL through EQ-5D-3L with visual analogic scale (VAS). Quality of life scores were registered at baseline and every eight weeks thereafter.

Treatment consisted of intravenous panitumumab 6 mg/kg q2w, administered in one hour the first day and in 30 minutes thereafter (if no infusional reaction was observed) plus intravenous paclitaxel 80 mg/m2 weekly administered one hour after panitumumab in one hour infusion, until progression or unacceptable toxicity. Panitumumab does not require prophylactic premedication from the first infusion.

Eligibility Criteria:
Inclusion Criteria:

* Signed Inform Consent
* Age \> 18 years
* Histologically or cytologically confirmed SCCHN
* Diagnosis of metastatic disease by the investigator and/or recurrent disease determined to be incurable by surgery or radiotherapy
* Subjects who have received radiation as primary therapy are eligible if radiation therapy treatment was completed \> 4 weeks prior to inclusion
* Subjects who have previously received chemotherapy as part of the initial multimodality treatment for locally advanced disease are eligible if the chemotherapy was completed \> 24 weeks prior to inclusion
* At least 1 unidimensionally measurable lesion of ≥ 20 mm using conventional techniques or ≥10 mm with spiral CT scan. Target lesions must not be chosen from a previously irradiated field unless there had been documented tumour progression in that lesion prior to inclusion
* Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 at screening
* Haematological function:

  * ANC ≥ 1.5 x 109 cells/L
  * Hemoglobin ≥ 9.0 g/dL
  * Platelet count ≥ 100 x 109/L
* Kidney function:

  o Adequate renal function with creatinine clearance ≥ 60 mL/min)
* Liver function:

  * AST ≤ 3 x ULN (if liver metastases, ≤ 5 x ULN)
  * ALT ≤ 3 x ULN (if liver metastases, ≤ 5 x ULN)
  * Bilirubin ≤ 2 x ULN
* Metabolic function:

  * Magnesium ≥ lower limit of normal,
  * Calcium ≥ lower limit of normal

Exclusion Criteria:

* Documented or symptomatic central nervous system metastases
* Nasopharyngeal carcinoma
* History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest scan
* History of another primary cancer, except:

  * Curatively treated in situ cervical cancer, or
  * Curatively resected non-melanoma skin cancer or
  * Other primary solid tumour curatively treated with no known active disease present and no treatment administered for ≥ 3 years prior to starting the study treatment. In that case confirmation of inclusion by the sponsor is required.
* Clinically significant cardiovascular disease ≤ 1 year prior to starting the study treatment
* Pulmonary embolism, deep vein thrombosis, or other significant thromboembolic event ≤ 8 weeks prior to starting the study treatment
* Symptomatic peripheral neuropathy of Grade ≥ 2 based on the CTCAE v3.0
* Subjects not recovered from all previous acute radiotherapy-related toxicities to ≤ grade 1
* History of severe skin disorder that in the opinion of the investigator may interfere with study conduct
* Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection
* Active infection requiring systemic treatment or any uncontrolled infection ≤ 14 days prior to starting the study treatment
* History of interstitial pneumonia or pulmonary fibrosis or signs of interstitial pneumonia or pulmonary fibrosis on the baseline chest X-ray.
* Known allergy or hypersensitivity to panitumumab, or other study medications.
* Prior anti epidermal growth factor receptor (EGFr) antibody therapy or treatment with small molecule EGFr inhibitors unless received as part of prior multimodality treatment and completed \> 24 weeks prior to starting the study treatment. In this case, the investigator should confirm that the subject had not presented any previous cetuximab-related infusion reaction \> grade 2.
* Subject is currently enrolled in or ≤ 30 days since ending other investigational device, investigational procedure, or drug study(s), or subject is receiving other investigational agent(s)
* Subjects requiring use of immunosuppressive agents, however, corticosteroids are allowed
* Man or woman of child-bearing potential who do not consent to use adequate contraceptive precautions during the course of the study, and for 6 months after the last study drug administration for women, and 3 months for men.
* Female subject who is pregnant or breast-feeding, or planning to become pregnant within 6 months after the end of treatment.
* Major surgery requiring general anesthesia/ spinal anesthesia and a significant incision ≤ 28 days or minor surgery ≤ 14 days prior to starting the study treatment. Subjects must have recovered from surgery-related toxicities.
* Subjects who do not wish to meet the study requirements or are unable to do so.