Clinical trial NCT01129154: Panitumumab (Vectibix®) in Cutaneous Squamous Cell Carcinoma (SCC)
Official title: An Open Label Multicentric Phase II Study of Panitumumab (Vectibix®) in Cutaneous Squamous Cell Carcinoma (SCC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Carcinoma, Squamous Cell
Keywords: Squamous cell carcinoma
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
Collaborators: name: Cliniques Universitaires UCL de Mont-Godinne, Dr Joseph Kerger
name: Cliniques Saint-Pierre Ottignies, Dr Lionel Duck
First posted: 2010-05-24
Enrollment: 17
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: Squamous Cell Carcinoma (SCC) is one of the most common malignancies in caucasian population. The effect of the immune system on the development of skin tumors has been demonstrated in transplant patients taking immunosuppressive agents (65 fold risk increase). It has been reported that activation of EGFR and RAS signaling pathways play an important role in disease progression maybe through downregulation of the immune system.

The investigators want to treat unresectable SCC patients with an antibody against EGFR (Vectibix®, panitumumab). This antibody induces tumor regression in metastatic colorectal cancer and has been approved as single agent for this indication.

The investigators want to measure the response rate but also analyze the modification of expression profile of some key proteins involved or supposed to be involved in the signaling pathways of EGFR and in the regulation of the immune system. Chemokines such as CCL27 have been shown to play a critical role in the skin-associated immune response by regulating T cell homing. Pivarcsi et al have reported that downregulation of CCL27 is mediated by activation of EGFR/RAS/MAPK signaling pathways.

Detailed description: This is an open-label, multicentric study of 17 patients with skin squamous cancer cell.

Eligible patients should not be suitable for immediate surgery. If they have only one tumor, it should be greater than 3 cm2 in order to allow multiple biopsies.

Patients will receive six infusions of Panitumumab 6 mg/kg every 2 weeks or until progression if earlier.

Patients will be assessed at baseline, at week 6 and then every 12 weeks till progression. In addition to clinical examination, evaluation tools will include photography and CT-scan, MRI or PET-scan.

Skin and tumor biopsies will be performed during first cycle at baseline and at days 2, 4, 8, 43, 85. Blood collections for translational research will be done during first cycle at baseline and at days 2, 4, 8,15, 43, 85. Blood collection for hematology and chemistry assessment will be done each 4weeks.

Patients presenting with a stable disease or a tumor response at week 12 will be eligible for maintenance cycles consisting in an infusion of panitumumab every 2 weeks till progression.

Eligibility criteria: Inclusion criteria

* Patient with histologically confirmed diagnosis of SCC.
* Patient must not be candidate to direct curative surgery.
* Tumor evaluation by photography with a ruler and CT-scan, MRI or PET-scan must be performed before enrollment.
* Age ≥ 18 years.
* Karnofsky Performance status (KPS) ≥70.
* Normal laboratory values:

  * Platelet count ≥100x103/μL
  * Leucocyte count ≥ 3x103/μL
  * Hemoglobin ≥ 9 g/dL
  * ASAT and ALAT ≤ 2.5xUNL
  * Serum creatinine ≤1.5xUNL
  * Total bilirubin ≤ 1.5xUNL
  * Magnesium ≥ Lower Normal Limit (LLN)
  * Calcium ≥ Lower Normal Limit (LLN)
* Patient should agree to perform biopsies and blood collections for translational research.
* Signed informed consent from the patient or legal representative must be obtained.

Exclusion criteria

* Clinically significant cardiovascular disease (including cardiac insufficiency NYHA grade III and IV, unstable angina, arrythmia, myocardial infarction, symptomatic congestive heart failure)in the past 12 months before enrollment.
* History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
* No prior chemotherapy.
* Prior anti-EGFR therapy.
* Radiation within four weeks prior to trial entry.
* Subject pregnant or breastfeeding, or planning to become pregnant within 6 months after the end of treatment.
* Subject (male or female) not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months after the end of treatment.
* The patient has (or has had) previous or concomitant malignancies at other sites within last 5years, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: via imaging every 12 weeks
Secondary outcomes:
measure: To assess the safety profile of panitumumab in SCC
timeFrame: at each visit
measure: Time to treatment failure (TTF)and Time to treatment progression TTP
timeFrame: via imaging, every 12 weeks
measure: To measure the duration of response.
timeFrame: via imaging, every 12 weeks
measure: To explore the gene expression profiles in SCC under panitumumab treatment (i.e CCL27, EGFR,…).
timeFrame: Skin and tumor biopsies will be performed at baseline and at days 2, 4, 8, 43, 85. Blood will be collected at baseline and at days 2, 4, 8, 43, 85
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc Université Catholique de Louvain
city: Mont Godinne
country: Belgium
facility: Cliniques Universitaires UCL
city: Ottignies
country: Belgium
facility: Cliniques Saint-Pierre
Study officials:
affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Baurain Jean-Francois, Md,PhD
role: PRINCIPAL_INVESTIGATOR
References: