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Penile CarcinomaPhase 2HERCULESNCT04224740

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

A Phase 2 study testing Pembrolizumab in people with Penile Carcinoma, run by Latin American Cooperative Oncology Group at 11 sites in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Penile Carcinoma
What is being tested?
Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
11 sitesBrazil
Study dates
15 Jun 2020to 13 Nov 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is expecting to father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
  • Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subject who are MSD employees directly involved in the conduct of the trial.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Brazil11 sites

  • Hospital de Amor de Barretos

    Barretos, São Paulo, 14.784-400

  • INCA - Instituto Nacional de Câncer

    Barretos, São Paulo, 20.230-130

  • COB - Clínica Oncológica do Brasil

    Belém, Pará, 66.053-000

  • Hospital Universitário de Brasília (HUB-UnB)

    Brasília, Federal District, 70.840-901

  • Hospital Erasto Gaertner

    Curitiba, Paraná, 81.520-060

  • Oncocentro Ceará (Rede D'or)

    Fortaleza, Ceará, 60.135-237

  • ICC - Instituto do Câncer do Ceará

    Fortaleza, Ceará, 60.430-230

  • Hospital Amaral Carvalho de Jaú

    Jaú, São Paulo, 17.210-070

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

    Porto Alegre, Rio Grande do Sul, 90.619-900

  • ICESP - Instituto do Câncer do Estado de São Paulo

    São Paulo, 01.246-000

  • BP - A Beneficência Portuguesa de São Paulo

    São Paulo, 01.323-030

Other trials in Brazil

About this study

Official title: A Phase II Trial of Pembrolizumab Combined With Cisplatin-based Chemotherapy as First-line Systemic Therapy in Advanced Penile Cancer

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.

Read the detailed description

Advanced penile squamous cell carcinoma is associated with dismal survival rates and a major impact on the quality of life. To date, unresectable or metastatic disease is managed by systemic therapy with platinum-based chemotherapy for patients with good performance status. The median PFS and OS on first-line platinum-based chemotherapy vary between 3-4 and 7-15 months, respectively. Chemotherapy induces objective responses in only 20-30% of penile cancer patients with rare complete responses and systemic treatment has not changed for decades. Therefore, this study's rationale is to explore the efficacy and safety of pembrolizumab combined with standard-of-care cisplatin(or carboplatin) plus 5-fluorouracil as part of the first-line therapy. Patients will receive pembrolizumab 200mg IV every three weeks with a maximum duration of 2 years (34 cycles-counting the combination with chemotherapy) in case of no progressive disease or intolerance. The investigators hypothesized that the combination of immunotherapy with standard cytotoxic chemotherapy may improve the overall response rate by RECIST v1.1 in this patient population.

Being tested
Pembrolizumab, Standard of care therapy
Keywords
Penile Neoplasms
Medical subject headings
Penile Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    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)

  • Standard of care therapyDrug

    Also called Cisplatin(or Carboplatin), 5-fluouracil

    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

Study groups in NCT04224740
Study groupRoleWhat they receive
Pembrolizumab plus standard of care chemotherapyExperimental-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
Receives: Drug: Pembrolizumab; Drug: Standard of care therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR)

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

    Measured: 24 weeks

Secondary outcomes (4)

  1. Progression Free Survival (PFS)

    Time from enrollment to progression by investigator-assessed RECIST 1.1 or death

    Measured: 24 months

  2. Overall survival (OS)

    Time from enrollment to death due to any cause.

    Measured: 36 months

  3. Clinical Benefit Rate (CBR)

    Proportion of patients who have complete, partial response or stable disease by investigator-assessed RECIST v1.1

    Measured: 24 weeks

  4. Health Related Quality of Life (QoL)

    Comparison of initial and final scores of the European Organization for Research and Treatment (EORTC) C30 questionnaires.

    Measured: 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2020
  2. Study start15 Jun 2020
  3. Primary completion13 Nov 2023
  4. Study completion13 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04224740
Sponsor's protocol ID
LACOG 0218
Acronym
HERCULES
Status last verified
Mar 2024
First submitted
3 Jan 2020
Last updated
13 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40965911

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab in people with Penile Carcinoma, run by Latin American Cooperative Oncology Group at 11 sites in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04224740, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2024.

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