Dacomitinib (PF-00299804) in Advanced/Metastatic Squamous Cell Carcinoma of the Penis

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano32 enrolled

Overview

Penile squamous cell carcinoma (SCC) is a very rare disease and prognosis depends primarily on regional lymph-node involvement. Despite the fact that cure can be obtained in patients with low metastatic load (pN1) by monotherapy, combination therapy is required for more advanced cases. Medical treatment options only for advanced or metastatic penile SCC are not very effective so far and the few chances for cure are solely dependent on multimodality treatment, either with surgery or radiation. Based on the observation that the epidermal growth factor receptor (EGFR) is almost invariably expressed in penile SCC and assuming similarities to the SCC of head and neck district, anti-EGFR targeted monotherapy has been investigated with promising early results at Istituto Tumori Milan and University of Texas MD Andreson Cancer Center. These premises lend support to the use of the pan-HER inhibitor dacomitinib for advanced or metastatic penile SCC.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Penile Neoplasms Carcinoma, Squamous Cell

Interventions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients must provide written informed consent * Eastern Cooperative Oncology Group performance status of at least 1 * Cytologically or histologically proven diagnosis of SCC of the penis * Uni- or bidimensionally measurable disease as defined by RECIST v1.1 criteria * Clinical stage N2-3 and/or M1 (TNM 2002) * Locoregional relapse after prior major surgery/ies (either single or multiple) * No prior systemic therapy except for the administration of vincristine-bleomycin-methotrexate (VBM) chemotherapy for superficial disease if administered at least 6 months prior to study enrollment * Adequate bone marrow, liver and renal function Exclusion Criteria: * Central nervous system (CNS) metastases or leptomeningeal carcinomatosis * History of active serious cardiovascular, cerebrovascular, pulmonary co-morbidities * Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma or any cancer curatively treated \> 5 years prior to study entry.

Outcomes

Primary Outcomes

The primary outcome measure will be the assessment of response-rate (RR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

RR (%) = complete response (CR) + partial response (PR), where CR is the disappearance of all target lesions (any pathological lymph-nodes must have reduction in short axis to \< 10 mm) and PR indicates at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.

Time frame: 2-months

Secondary Outcomes

To assess the safety and tolerability of the study drug. Incidence, nature and severity of treatment-related adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

Time frame: 2-months

Pathologic complete response (pCR) rate for patients undergoing surgery in the treatment time course.

Time frame: 2-months or longer.

Progression-free survival.

Time frame: 2-months.

Overall Survival

Time frame: 6-months

Variations of the Quality of Life score as assessed with the Edmonton Symptom Assessment Scale (ESAS), validated in Italian language.