Panitumumab (Vectibix®) in Cutaneous Squamous Cell Carcinoma (SCC) (PASCE)

An Open Label Multicentric Phase II Study of Panitumumab (Vectibix®) in Cutaneous Squamous Cell Carcinoma (SCC)

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.

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Squamous Cell
• Intervention / Treatment: Drug: infusions of Panitumumab

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.

• Study Type: Interventional
• Enrollment (Anticipated): 17
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Baurain Jean-François, MD, PhD; Phone Number: +32 2 7645427; Email: jean-francois.baurain@uclouvain.be
• Study Contact Backup: Name: Duquenne Aline, MSc; Phone Number: +32 2 7645427; Email: aline.duquenne@uclouvain.be

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires Saint-Luc Université Catholique de Louvain
    • Contact: Baurain Jean-Francois, Md,PhD; Phone Number: +32 2 7645427; Email: jean-françois.baurain@uclouvain.be
    • Contact: Duquenne Aline, MSc; Phone Number: +32 2 764 5427; Email: aline.duquenne@uclouvain.be
  • Mont Godinne, Belgium, 5530
    • Recruiting
    • Cliniques Universitaires UCL
    • Contact: Kerger Joseph, MD, PhD; Phone Number: +32 81423328
  • Ottignies, Belgium, 1340
    • Recruiting
    • Cliniques Saint-Pierre
    • Contact: Duck Lionel, MD; Phone Number: +32 10414953

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: panitumumab; Patients will receive six infusions of panitumumab every 2 weeks for the first cycle.	Drug: infusions of Panitumumab; Patients will receive six infusions of Panitumumab 6 mg/kg every 2 weeks or until progression if earlier.; Other Names: Vectibix®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	To measure the efficacy of Panitumumab for SCC in terms of Overall Response Rate (ORR). Overall Response Rate (ORR) is defined as the sum of complete and partial tumour responses seen, divided by the total number of evaluable patients.	via imaging every 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the safety profile of panitumumab in SCC	Proportion of all adverse events will be reported. CTC scale 3.0 will be used with the exception of skin- or nail-related toxicities, which must be graded using CTC version 3.0 with modifications (Appendix E). Patients will be followed for safety until closure of study.	at each visit
Time to treatment failure (TTF)and Time to treatment progression TTP	Time to treatment failure (TTF) is defined as the time from date of first dose of study medication to first occurrence of any following event : documentation of objective tumor progression, toxicities requiring prematurely stop of treatment or death. TTF will be calculated according to the Kaplan-Meier technique. Time to Progression will also be calculated. Subjects without evidence of progression at the end of follow up will be considered as censored.	via imaging, every 12 weeks
To measure the duration of response.	Duration of overall response will be measured according RECIST guidelines version 1.1 Duration of response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study).	via imaging, every 12 weeks
To explore the gene expression profiles in SCC under panitumumab treatment (i.e CCL27, EGFR,…).	Results will be presented as proportion of each expression type.	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

Collaborators and Investigators

• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Collaborators: Cliniques Universitaires UCL de Mont-Godinne, Dr Joseph Kerger; Cliniques Saint-Pierre Ottignies, Dr Lionel Duck
• Investigators: Principal Investigator: Baurain Jean-Francois, Md,PhD, Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Anticipated): July 1, 2012
• Study Completion (Anticipated): July 1, 2012

Study Registration Dates

• First Submitted: May 21, 2010
• First Submitted That Met QC Criteria: May 21, 2010
• First Posted (Estimate): May 24, 2010

Study Record Updates

• Last Update Posted (Estimate): August 30, 2010
• Last Update Submitted That Met QC Criteria: August 27, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Squamous cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Panitumumab
• Other Study ID Numbers: Luc 09-002