Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Penile Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Penile Diseases

Male Urogenital Diseases

Penile Cancer

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Pembrolizumab

Fluorouracil

Cisplatin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

-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

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)

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

Standard of care therapy

Fernando Cotait Maluf

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.

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.

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

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

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

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

Time from enrollment to death due to any cause.

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

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

Merck Sharp & Dohme LLC

Latin American Cooperative Oncology Group

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Avelumab

Immunomodulating Agents

Avelumab will be administered at a dose of 10 mg/kg every 2 weeks with appropriate supportive care

Elise Robert

Diane Berthod

Antoine THIERY-VUILLEMIN, MD

Patients with unresectable locally advanced or metastatic squamous cell penile carcinoma (SPC) who are in response or with stable disease after first line platinum containing polychemotherapy who meet the inclusion/exclusion criteria will be offered to take part in the study.

The patients may be pre-screened at the time of the 1st line chemotherapy.

In order for patients to be enrolled, the investigator must have carried out a radiological assessment of the disease during first line systemic treatment (a maximum of between 3 and 6 cycles): the cancer must be controlled. Patients with disease progression cannot be included in the PULSE study as this is a maintenance study.

After inclusion, Avelumab will be administered at a dose of 10 mg/kg, at a frequency of once every 2 weeks with appropriate supportive care.

Maintenance Avelumab Immunotherapy in Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma

Activity and Tolerability of Maintenance Avelumab Immunotherapy After First Line Polychemotherapy Including Platinum in Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma

To estimate progression-free survival in patients included in this study

To estimate overall survival in patients included in this study

To estimate the median duration of avelumab treatment calculated from avelumab initiation in patients included in this study

To assess health-related quality of life since avelumab is started in patients included in this study

To assess safety profile after avelumab initiation

Pfizer

Centre Hospitalier Universitaire de Besancon

Skin and Connective Tissue Diseases

Digestive System Diseases

Breast Neoplasms

Uterine Cervical Neoplasms

Melanoma

Vulvar Neoplasms

Squamous Cell Carcinoma of Head and Neck

Sarcoma

Anus Neoplasms

Skin Diseases

Breast Diseases

Head and Neck Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Vulvar Diseases

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Anus Diseases

Rectal Diseases

Soft Tissue Sarcoma

Anal Cancer

Vulvar Cancer

Anti-Infective Agents

Ganciclovir

Ganciclovir triphosphate

Antiviral Agents

Enzyme Inhibitors

Stimotimagene copolymerplasmid will be administered intratumoral once in a dose of 20 mkg of DNA per 1 cm3 of tumor (for cohort 1) and 40 mkg of DNA per 1 cm3 of tumor (for cohort 2).

Ganciclovir (Cimeven®) will be administrated intravenous twice a day at 12-hour intervals for 15 days.

Stimotimagene copolymerplasmid will be administered intratumorally twice with 5-day interval in the optimal dose selected at previous stage of the trial.

Ganciclovir (Cimeven®) will be administrated intravenous twice a day at 12-hour intervals for 15 days.

Stimotimagene copolymerplasmid will be administered intratumorally three times with 5-day interval in the optimal dose selected at first stage of the trial.

Ganciclovir (Cimeven®) will be administrated intravenous twice a day at 12-hour intervals for 15 days.

Intratumoral administration of gene therapy drug Stimotimagene copolymerplasmid

Intratumoral administration of Stimotimagene copolymerplasmid

Intravenous administration of prodrug Ganciclovir (Cymeven®)

Intravenous administration of Ganciclovir (Cymeven®)

Max Koksharov

Ludmila Zhukova

Igor Samoylenko

Lev Ashrafian

Aleksander Fedenko

The purpose of this study is to evaluate the safety and tolerability of different doses and administration regimens of Stimotimagene copolymerplasmid in patients with histologically confirmed diagnosis of solid tumor and/or its metastases.

Stimotimagene copolymerplasmid is an anti-tumor gene therapy drug, contains super-coiled plasmid DNA encapsulated in polycationic envelope (PPT: polyethyleneimine (PEI) - polyethylene glycol (PEG) - TAT peptide). The plasmid encodes two therapeutic genes: herpes simplex virus thymidine kinase (HSVtk) and human granulocyte-macrophage colony-stimulating factor (hGM-CSF). HSVtk converts the prodrug ganciclovir to a toxin in cells that have been transfected by Stimotimagene copolymerplasmid, GM-CSF stimulates proliferation and differentiation of antigen-presenting cells.

Stimotimagene copolymerplasmid therapy is two-staged: (1) intratumoral injection of Stimotimagene copolymerplasmid, (2) intravenous administration of ganciclovir (Cimeven®) This is the first-in-human study of Stimotimagene copolymerplasmid which will be conducted in three arms. In this study dose escalation (Arm1) and number of drug administrations (Arms 2 and 3) will be explored. All study parts will investigate the safety, tolerability and pharmacokinetic profile of Stimotimagene copolymerplasmid.

Safety, Tolerability and Pharmacokinetics Investigation of Stimotimagene Copolymerplasmid

An Open Multicenter Study of the Safety, Tolerability, and Pharmacokinetics of Different Doses of Stimotimagene Copolymerplasmid at Patients With Advanced-stage Solid Tumors With Cymeven® (Ganciclovir) Infusions

Assessment of presence/absence of dose-limiting toxicities (DLTs)

Assessment of frequency and severity of adverse events (CTCAE classification)

Assessment of number of cases of early termination of participation in the study due to the development of Serious Adverse Events and Other Adverse Events associated with the study therapy)

Assessment of quantitative content of plasmid DNA (pTKhGM) in patients' peripheral blood at:

Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Days 5, 7, 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 1st step of the study; Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Day 6 (before drug administration and 8 h after drug administration), Days 7, 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 2nd step of the study; Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Day 6 (before drug administration and 8 h after drug administration), Day 7, Day 11 (before drug administration and 8 h after drug administration), Days 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 3rd step of the

Assessment of quantitative content of plasmid DNA (pTKhGM) in patients' urine at:

Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Days 5, 7, 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 1st step of the study; Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Day 6 (before drug administration and 8 h after drug administration), Days 7, 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 2nd step of the study; Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Day 6 (before drug administration and 8 h after drug administration), Day 7, Day 11 (before drug administration and 8 h after drug administration), Days 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 3rd step of the study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab Combined With Cisplatin-based Chemotherapy as First-line Systemic Therapy in Advanced Penile Cancer	NCT04224740	Penile Carcinom...	Pembrolizumab Standard of car...	18 Years -	Latin American Cooperative Oncology Group
Maintenance Avelumab Immunotherapy in Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma	NCT03774901	Penile Cancer Penile Neoplasm... Penile Squamous...	Avelumab	18 Years -	Centre Hospitalier Universitaire de Besancon
Maintenance Avelumab Immunotherapy in Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma	NCT03774901	Penile Cancer Penile Neoplasm... Penile Squamous...	Avelumab	18 Years -	Centre Hospitalier Universitaire de Besancon
Maintenance Avelumab Immunotherapy in Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma	NCT03774901	Penile Cancer Penile Neoplasm... Penile Squamous...	Avelumab	18 Years -	Centre Hospitalier Universitaire de Besancon
Safety, Tolerability and Pharmacokinetics Investigation of Stimotimagene Copolymerplasmid	NCT05578820	Sarcoma Melanoma Squamous Cell C... Breast Neoplasm... Uterine Cervica... Vulvar Neoplasm... Penile Neoplasm... Anus Neoplasms	Intratumoral ad... Intravenous adm...	18 Years - 75 Years	Gene Surgery LLC
Pembrolizumab Combined With Cisplatin-based Chemotherapy as First-line Systemic Therapy in Advanced Penile Cancer	NCT04224740	Penile Carcinom...	Pembrolizumab Standard of car...	18 Years -	Latin American Cooperative Oncology Group

Spots Global Cancer Trial Database for penile neoplasms