Pembrolizumab Combined With Cisplatin-based Chemotherapy as First-line Systemic Therapy in Advanced Penile Cancer

NCT04224740 | Completed Phase 2

• 1 other identifier: LACOG 0218
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 11

Brief Summary

This is a phase II clinical trial evaluating activity, safety and patients reported outcomes of first-line pembrolizumab plus cisplatin (or carboplatin) plus 5-FU for patients with advanced penile squamous cell carcinoma. The primary endpoint is overall responsa rate according to RECIST v1.1 at week 24.

Conditions

Penile Carcinoma

Keywords

Penile Neoplasms

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Proportion of patients with partial or complete response by investigator-assessed RECIST v1.1

  24 weeks

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  24 months

• Overall survival (OS)

  36 months

• Clinical Benefit Rate (CBR)

  24 weeks

• Health Related Quality of Life (QoL)

  24 weeks

Study Arms (1)

Pembrolizumab plus standard of care chemotherapy

EXPERIMENTAL

-Pembrolizumab combined with standard of care therapy * Standard of care therapy: ciplastin 70mg/m² IV D1(or carboplatin AUC 5) plus 5-Fluouracil 1000mg/m²/day IV( continuous infusion on Days 1-4) Q3W for 6 cycles

Drug: Pembrolizumab; Drug: Standard of care therapy

Interventions

Pembrolizumab DRUG

Patients will receive pembrolizumab at the dose of 200mg IV Q3W with maximum duration of 2 years (34 cycles-counting the part combined with chemotherapy)

Pembrolizumab plus standard of care chemotherapy

Standard of care therapy DRUG

Ciplastin 70mg/m² IV D1(or carboplatin AUC 5) plus 5-Fluouracil 1000mg/m²/day IV( continuous infusion on Days 1-4) Q3W for 6 cycles

Also known as: Cisplatin(or Carboplatin), 5-fluouracil

Pembrolizumab plus standard of care chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male participants who are at least 18 years of age on the day of signing informed consent will be enrolled in this study.
• Patients with penile squamous cell carcinoma with either:
• metastatic disease (de novo or recurrent), or
• recurrent locally advanced disease not amenable to curative intent therapy (e.g. surgery, radiotherapy, chemoradiotherapy, etc), or
• anyT N3 M0 or T4 anyN M0 (stage IV - AJCC 8th) not amenable to curative-intent therapy (e.g. surgery, radiotherapy, chemoradiotherapy, etc).
• Histologically confirmed diagnosis of penile squamous cell carcinoma (PSCC).
• Patients with advanced or metastatic PSCC without prior treatment or that progressed after 12 months of (neo) adjuvant chemotherapy completion.
• Participant must agree to use a contraception.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
• Newly obtained biopsies are preferred to archived tissue.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of enrollment.
• Have adequate organ function (see Table 1). Specimens must be collected within 10 days prior to the start of study treatment.
• Have a life expectancy of at least 12 weeks.

You may not qualify if:

• Primary tumor arising from urethra.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to enrollment.
• Has received prior radiotherapy within 3 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of non-penile skin or carcinoma in situ that have undergone potentially curative therapy are not excluded.
• Has known symptomatic uncontrolled CNS metastases and/or carcinomatous meningitis.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV).
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection.

Sponsors & Collaborators

• Latin American Cooperative Oncology Group: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (11)

Oncocentro Ceará (Rede D'or)

Fortaleza, Ceará, 60.135-237, Brazil

Location

ICC - Instituto do Câncer do Ceará

Fortaleza, Ceará, 60.430-230, Brazil

Location

Hospital Universitário de Brasília (HUB-UnB)

Brasília, Federal District, 70.840-901, Brazil

Location

Hospital Erasto Gaertner

Curitiba, Paraná, 81.520-060, Brazil

Location

COB - Clínica Oncológica do Brasil

Belém, Pará, 66.053-000, Brazil

Location

CPO - Centro de Pesquisa em Oncologia do Hospital São Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, 90.619-900, Brazil

Location

Hospital de Amor de Barretos

Barretos, São Paulo, 14.784-400, Brazil

Location

INCA - Instituto Nacional de Câncer

Barretos, São Paulo, 20.230-130, Brazil

Location

Hospital Amaral Carvalho de Jaú

Jaú, São Paulo, 17.210-070, Brazil

Location

ICESP - Instituto do Câncer do Estado de São Paulo

São Paulo, 01.246-000, Brazil

Location

BP - A Beneficência Portuguesa de São Paulo

São Paulo, 01.323-030, Brazil

Location

Related Publications (1)

• Cotait Maluf F, Trindade K, Preto D, de Almeida Luz M, Medeiros Milhomem Beato P, Assed Bastos D, Holanda Soares JP, Marcondes Lopes V, Werneck de Carvalho LE, Queiroz Borges Muniz D, Racy DJ, de Jesus RG, Rebelatto TF, Werutsky G, Halabi S, Sabino Marques Monteiro F, Poisl Fay A. Pembrolizumab Plus Platinum-Based Chemotherapy for Patients With Advanced Penile Cancer: The Nonrandomized HERCULES (LACOG 0218) Clinical Trial. JAMA Oncol. 2025 Nov 1;11(11):1314-1320. doi: 10.1001/jamaoncol.2025.3266.

  PMID: 40965911 DERIVED

MeSH Terms

Conditions

Penile Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Penile Diseases; Male Urogenital Diseases

Study Officials

• Fernando Cotait Maluf

  Latin American Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2020
• First Posted: January 13, 2020
• Study Start: June 15, 2020
• Primary Completion: November 13, 2023
• Study Completion: November 13, 2023
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (11)