A Phase 2 clinical study to assess efficacy of induction carboplatin/paclitaxel + pembrolizumab for locoregionally advanced penile cancer: PRIAM

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

13 Aug 2024 → ongoing

Decision date (initial)

2025-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Pathological complete response (pCR)

Secondary objectives 2

1. Establish safety of pre-operative CP+P treatment in penile cancer patients
2. Establish durability of clinical benefit after pre-operative CP+P

Conditions and MedDRA coding

locoregionally advanced penile cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male patients of more than 18 years of age
2. Histologically confirmed diagnosis of squamous cell carcinoma of the penis
3. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
4. Patients have one of the following disease stages: - cTxN2-3 or - cTxN1 in case of central nodal necrosis and/or an irregular nodal border, or node >3cm, or - Inguinal or pelvic lymph node recurrence that is potentially resectable. Any of the disease stages above, in combination with oligometastatic disease with a maximum of 2 distant metastases is allowed, as long as these metastases can be treated by resection or radiotherapy. This should be established in the multidisciplinary tumor board before enrolment.
5. Archival tumor tissue sample or newly obtained [core, incisional or excisional] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
6. A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 14 days prior to the first dose of study intervention.
8. Have adequate organ function as defined in the protocol. Specimens must be collected within 14 days prior to the start of study intervention.

Exclusion criteria 19

1. 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
2. Has received prior systemic anti-cancer therapy including investigational agents, or an investigational device, within 4 weeks prior to registration
3. Has received prior radiotherapy within 4 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids
4. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Note: please refer to Section 5.5.2 for information on COVID-19 vaccines
5. 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.
6. Known additional malignancy that is progressing or has required active treatment within the past 3 years. Exceptions: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Patients with low-risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
7. Has known active or treated CNS metastases and/or carcinomatous meningitis.
8. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
9. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid). Patients with vitiligo, psoriasis or other mild skin disease can still be included.
10. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
11. Has an active infection requiring systemic therapy.
12. Has a known history of Human Immunodeficiency Virus (HIV) infection.
13. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and/or Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Hepatitis B and C screening tests are not required unless a patient has a known history of HBV or HCV infection. Participants must have completed curative anti-viral therapy at least 6 months prior to randomization.
14. Has not adequately recovered from major surgery or has ongoing surgical complications.
15. Major pelvic surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for the disease under study.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
18. 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.
19. Has had an allogenic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy, defined as pathological complete response (pCR) in all patients who are evaluable for response

Secondary endpoints 4

1. All-grade toxicity and treatment-related grade 3/4 toxicity by NCI-CTC-V5 will be reported in all patients who received at least one cycle of treatment
2. Progression-free survival, measured from day 1 of study therapy in all patients who were registered for the study and started treatment.  Overall survival, measured from day 1 of study therapy, in all patients who were registered for the study and started treatment.
3. Overall survival, measured from day 1 of study therapy, in all patients who were registered for the study and started treatment.
4. PFS and OS will be assessed at the primary analysis and at any later time point. Survival data will be reported as Kaplan-Meier curves. Additionally, median PFS or OS and PFS or OS at fixed time points (eg 1,2 or 3 years) may be reported.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Michiel van der Heijden

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Michiel van der Heijden

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications