Efficacy and Safety of Dacomitinib in the Treatment of Skin Squamous Cell Cancer

Efficacy and Safety of Single Agent Pan-HER Inhibitor Dacomitinib in the Treatment of Locally Advanced Unresectable or Metastatic Squamous Cell Cancer of the Skin or With Clinical Contraindication to Surgery

This is an open label, monocentric, uncontrolled phase II trial with Dacomitinib, a pan-HER inhibitor, in unresectable or metastatic skin SCC.

HER2 expression is common in skin SCC, being reported with high rates, even if in small studies.

Coexpression of EGFR, HER2 and HER3 is present in skin SCCs but not in normal skin and it could be associated with the malignant phenotype. In this frame Dacomitinib could play a role in the increase of the response rate.

Study Overview

• Status: Unknown
• Conditions: Skin Squamous Cell Cancer
• Intervention / Treatment: Drug: Dacomitinib

Detailed Description

The patients will assume Dacomitinib 30 mg daily for the first 2 weeks. If the highest skin toxicity will be of grade <2, then the patients will start dacomitinib at 45 mg once daily and they will be clinically assessed every cycle (i.e. every 28 days).

If the highest skin toxicity will be grade >2, then the patient will interrupt the treatment following the criteria for dose reduction.

Tumor evaluation will be performed at baseline and every other cycle. Response will be assessed according to RECIST 1.1. The patient will continue to assume the study drug until disease progression, unacceptable toxicity or any medical condition that will suggest to stop the treatment for patient's safety

• Study Type: Interventional
• Enrollment (Anticipated): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

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:

• Signed informed consent to treatment
• Histological diagnosis of squamous cell carcinoma of the skin not amenable to surgical treatment with curative purposes or with clinical contraindication to surgery (examples of medical contraindications to surgery include but are not limited to: skin SCC that has recurred in the same location after two or more surgical procedures and curative resection is deemed unlikely; anticipated substantial morbidity and/or deformity from surgery (e.g., removal of all or part of a facial structure, such as nose, ear, eyelid, eye; or requirement for limb amputation); anticipated difficulty in obtaining a curative resection due to the location of the tumour, the size of disease; anticipated difficulty in reconstructing the area that will be surgically removed; significant comorbidities that preclude the feasibility of a radical surgery
• Presence of measurable disease according to RECIST 1.1
• ECOG performance status 0-2
• Age≥ 18 years
• For men and women in the fertile period: the use of birth control systems during treatment

Exclusion Criteria:

• Previous treatment with tyrosine kinase inhibitors or monoclonal antibodies directed against EGFR
• Any toxicity CTC grade> 2 from previous treatments not yet resolved
• Pregnant or breastfeeding

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: Dacomitinib; Patients will assume Dacomitinib 30 mg daily for the first 2 weeks. If the highest skin toxicity will be of grade <2, then the patients will start dacomitinib at 45 mg once daily and they will be clinically assessed every cycle (i.e. every 28 days). If the highest skin toxicity will be grade >2, then the patient will interrupt the treatment following the criteria for dose reduction.

Drug: Dacomitinib; The patients will assume Dacomitinib 30 mg daily for the first 2 weeks. If the highest skin toxicity will be of grade <2, then the patients will start dacomitinib at 45 mg once daily and they will be clinically assessed every cycle (i.e. every 28 days). If the highest skin toxicity will be grade >2, then the patient will interrupt the treatment following the criteria for dose reduction.; Other Names: PF-00299804

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate to Dacomitinib	Response rate (partial response, PR + complete response, CR) to Dacomitinib	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance to the treatment and safety	Compliance to the treatment and safety	24 months
Disease control	Disease control (stable disease (SD) + PR + CR)	24 months
PFS and OS	Progression-Free Survival (PFS) and Overall Survival (OS)	24 months
Percentage of patients initially not considered for surgery due to difficulty to obtain a curative treatment that undergo surgery after dacomitinib	Percentage of patients initially not considered for surgery due to difficulty to obtain a curative treatment that undergo surgery after dacomitinib	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of mutational/gene expression	Translational research regarding the analysis of pERK, Ki67, pSTAT3 p27, pEGFR and other mutational/gene expression analysis to be determined within the study period. Correlation of immunohistochemistry analysis of these markers and response to treatment or to onset of acquired resistance.	24 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): November 1, 2016
• Study Completion (Anticipated): November 1, 2016

Study Registration Dates

• First Submitted: August 9, 2014
• First Submitted That Met QC Criteria: October 16, 2014
• First Posted (Estimate): October 20, 2014

Study Record Updates

• Last Update Posted (Estimate): July 4, 2016
• Last Update Submitted That Met QC Criteria: July 1, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: skin squamous cell cancer panHER inhibitor Dacomitinib
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma, Squamous Cell; Neoplasms, Squamous Cell
• Other Study ID Numbers: DACOMINT14; 92/14 (Other Identifier: INT)