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

Conditions

Carcinoma, Squamous Cell, Penile Neoplasms

Keywords

Molecular Targeted Therapy, Neoadjuvant therapy, Dacomitinib

Brief summary

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.

Necchi A, Lo Vullo S, Perrone F, Raggi D, Giannatempo P, Calareso G, Nicolai N, Piva L, Biasoni D, Catanzaro M, Torelli T, Stagni S, Togliardi E, Colecchia M, Busico A, Gloghini A, Testi A, Mariani L, Salvioni R.

2017-10-0468 citations

10.1111/bju.14013

Abstract CT139: First-line therapy with dacomitinib, an orally available pan-her tyrosine kinase inhibitor, for locally-advanced or metastatic penile squamous cell carcinoma: Results of an open label, single-arm, single-center, phase 2 study

Andrea Necchi, Salvatore Lo Vullo, Daniele Raggi, Patrizia Giannatempo, Nicola Nicolai et al. (12 authors)

Cancer Research2017-07-01

10.1158/1538-7445.am2017-ct139

Dacomitinib (Daco) induction therapy for locally advanced (LA) or metastatic penile squamous cell carcinoma (PSCC): An open label, single-arm, phase II study.

Andrea Necchi, Salvatore Lo Vullo, Daniele Raggi, Patrizia Giannatempo, Nicola Nicolai et al. (19 authors)

Journal of Clinical Oncology2017-02-202 citations

10.1200/jco.2017.35.6_suppl.399

Pan-HER tyrosine-kinase inhibitors (TKI) dacomitinib and afatinib in penile squamous cell carcinoma (PSCC): Results from an ongoing open-label, single-group, phase 2 trial of dacomitinib in chemonaive patients (pts).

Daniele Raggi, Andrea Necchi, Patrizia Giannatempo, Nicola Nicolai, Maurizio Colecchia et al. (13 authors)

Journal of Clinical Oncology2016-01-10

10.1200/jco.2016.34.2_suppl.483

Dacomitinib (PF-0299804) in untreated patients (pts) with advanced or metastatic penile squamous cell carcinoma (PSCC): Early findings of an open-label, single-group, phase II trial (HER-Uro01).

Andrea Necchi, Patrizia Giannatempo, Daniele Raggi, Nicola Nicolai, Tullio Torelli et al. (15 authors)

Journal of Clinical Oncology2015-03-011 citations

10.1200/jco.2015.33.7_suppl.384

Interventions

DRUGDacomitinib

PF-299804 will be administered orally at a dose of 45 mg/day continuously until surgery, evidence of disease progression or onset of unacceptable toxicity.

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 75 Years

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
The primary outcome measure will be the assessment of response-rate (RR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	2-months	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.

Secondary

Measure	Time frame
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.	2-months
Pathologic complete response (pCR) rate for patients undergoing surgery in the treatment time course.	2-months or longer.
Progression-free survival.	2-months.
Overall Survival	6-months
Variations of the Quality of Life score as assessed with the Edmonton Symptom Assessment Scale (ESAS), validated in Italian language.	2-months.

Countries

Italy

Outcome results

None listed