PULSE : Activity and tolerability of maintenance avelumab immunotherapy after first line polychemotherapy including a platinum salt in patients suffering from locally advanced or metastatic squamous cell penile carcinoma (SPC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Universitaire

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

18 Dec 2025 → ongoing

Decision date (initial)

2024-12-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514997-27-00

EudraCT number

2018-001427-38

ClinicalTrials.gov

NCT03774901

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the benefit of maintenance treatment with avelumab measured by disease-free survival (DFS) in patients suffering from unresectable locally advanced or metastatic SPC whose disease has not progressed after completion of first line chemotherapy including cisplatin.

Secondary objectives 10

1. To assess the benefit of maintenance treatment with avelumab, measured from DFS according to iRECIST in patients suffering from unresectable, locally advanced or metastatic SPC whose disease has not progressed after first line poly-chemotherapy containing a platinum salt
2. To assess the benefit of maintenance treatment with avelumab, measured from overall survival (OS) in patients suffering from unresectable, locally advanced or metastatic squamous cell penile carcinoma (SPC) whose disease has not progressed after first line polychemotherapy including a platinum salt
3. To assess the percentage of patients still alive at 12 months
4. To assess the duration of treatment with avelumab
5. To assess DFS and OS of avelumab in patients with a tumour which is positive for PD-L1 and in all patients
6. To assess the overall safety profile of avelumab.
7. To assess the effect of avelumab on patients’ health-related quality of life.
8. To assess the time until subsequent first and second systemic therapy (TJPTSU; TJDTSU)
9. To assess the duration of administration of the first subsequent systemic therapy
10. To estimate the time to deterioration of quality of life

Conditions and MedDRA coding

cell penile carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Men, 18 years old and older
2. Histologically confirmed unresectable locally advanced or metastatic squamous cell penile carcinoma
3. Patients who have received a minimum of 3 and a maximum of 6 cycles of polychemotherapy including a platinum salt (cisplatin or carboplatin) administered as 1st line systemic treatment. In case of weekly or bi-monthly chemotherapy injection, the duration of one cycle can be of 3 weeks or 4 weeks depending on the drugs and doses prescribed. In the event of pretreatment with cisplatin: a cumulative minimum dose of 210 mg/m2 is required in order to be eligible. In the event of pretreatment with carboplatin: a minimum cumulative dose equivalent to 3 cycles of carboplatin AUC5 is required to be eligible.
4. Patients without disease-progression according to the RECIST v1.1 criteria (i.e. in complete or partial response or stable disease at inclusion) after 3 to 6 cycles of 1st line chemotherapy. Eligibility based on this criterion will be established locally by the investigator by examining pre and post-chemotherapy radiological assessments (CT/MRI)
5. Estimated life expectancy of at least 3 months
6. ECOG (Eastern Cooperative Group) performance status of 0 to 1
7. Adequate bone marrow function: a – absolute neutrophil (NP) count ≥ 1500/mm3 or ≥ 1.5x109/L b – platelets ≥ 100 000/mm3 or ≥ 100.109/L c – haemoglobin ≥ 9 g/dL (the patient may have been transfused)
8. Adequate renal function defined by a creatinine clearance of ≥ 30 m/min (according to the MDRD equation)
9. Adequate liver function: a – total serum bilirubin ≤ 1.5 times ULN (upper limit of normal), except in cases of Gilbert’s disease when the authorised limit is ≤ 2 ULN b - AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 2.5 times ULN; the accepted limit in patients with liver metastases is ≤ 5 times ULN

Exclusion criteria 24

1. Patients who have never received chemotherapy with a platinum salt (cisplatin or carboplatin)
2. Patients who have received more than one previous line of systemic treatment for penile cancer with the exception in case of a delay of more than 12 months between the end of a prior treatment and the start of the platinum based polychemotherapy
3. Patients whose disease has progressed according to RECIST v1.1 criteria after 1st line chemotherapy for penile cancer. The cancer must not be in the progression phase at inclusion.
4. Past history of immunotherapy treatment with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or an anti- CTLA-4 antibody (including ipilimumab) or any other antibody or medicinal products specifically targeting anti-cancer immunotherapy.
5. Major surgery within 4 weeks or major radiotherapy within 2 weeks prior to starting avelumab. Previous palliative radiotherapy (≤ 10 fractions) for metastatic lesions is permitted provided that this has been completed at least 48 hours prior to starting avelumab.
6. Patients with a past history of known central nervous system metastases, meningeal carcinomatosis or spinal compression
7. Persistent toxicity (excluding alopecia) due to previous treatment, NCI CTCAE v4.0 Grade> 1. Grade ≤2 sensory neuropathy, however is acceptable. If other residual grade ≤2 toxicities persist but do not carry a risk of decompensation on avelumab according to the investigator potential inclusion may be discussed with the sponsor.
8. Existence of a past history of cancer within 3 years prior to inclusion into the study (excluding cured localised cancer such as non-melanomatous skin cancers, superficial bladder cancers and localised prostate cancer with undetectable PSA).
9. Participation in another interventional study with a systemic anti-cancer treatment within 4 weeks prior to inclusion. Inclusion in observational or interventional studies not involving a health product is permitted. Patients with telephone follow up of toxicities and simple laboratory monitoring or other questionnaires alone may be included
10. Active auto-immune disease which may deteriorate following administration of an immunostimulatory agent. Patients suffering from type I diabetes, vitiligo, psoriasis or hypo or hyperthyroidism not requiring immunosuppressant treatment are eligible.
11. Patients with uncontrolled adrenal failure.
12. Any of the following events in the 3 months prior to inclusion: myocardial infarction, severe/unstable angina, coronary/periphery artery bypass, symptomatic congestive heart failure, cerebrovascular accident, transient ischaemic attack.
13. Pulmonary embolism or deep vein thrombosis within 3 months prior to inclusion (unless if stable, asymptomatic and treated with a low molecular heparin for at least 10 days prior to starting the avelumab).
14. Active infection requiring systemic treatment
15. Known serious hypersensitivity reaction to monoclonal antibodies (grade ≤ 3), past history of anaphylaxis or uncontrolled asthma (i.e. three or more asthma symptom control factors according to the Global Initiative for Asthma, 2015).
16. Known prior severe hypersensitivity to investigational product (avelumab) or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
17. Current treatment with an immunosuppressant medicinal product or treatment within 7 days prior to inclusion, EXCEPT: a – Intra-nasal, inhaled or local steroids or local steroid injections (such as intra-articular injections) b - Systemic corticosteroids at physiological doses of ≤ 10 mg/day of prednisone or equivalent c - Steroids as premedication for hypersensitivity reactions (such as CT scan premedication).
18. Diagnosis of human immunodeficiency virus (HIV) infection or disease related to the acquired immunodeficiency syndrome (AIDS). In patients who are seropositive for HIV but have a disease deemed to be controlled on anti-viral therapy from the opinion of the patient’s HIV contact doctor: inclusion is still possible if the CD4 count is ≥ 300/mm3
19. Previous organ transplant including stem cell allotransplantation.
20. Any screening test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating active infection.
21. Vaccination within 4 weeks prior to the first administration of avelumab and throughout the period of the study, except with inactivated vaccines (such as, inactivated influenza vaccines).
22. Men of child-bearing age who do not wish or cannot use 2 methods of highly effective contraception (oral contraceptives, contraceptive injections, intra-uterine devices, dual barrier method or contraceptive patches) as described in the protocol throughout the study and for at least 60 days after the last dose of avelumab
23. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
24. People who are vulnerable under the law (minors, adults under legal protection, people deprived of their freedom)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-free progression (DFS): time period between the date of starting avelumab and the date of first progression (local, remote [measurement of disease according to RECIST v1.1 criteria], second cancer) or death regardless of cause. The patients lost to follow up and patients who are alive without disease progression will be censured at the date of last news.

Secondary endpoints 9

1. Overall survival (OS) defined as the time period between the date of starting treatment and the date of death, regardless of cause. Patients lost to follow up and those who are alive will be censured at the date of last news.
2. Proportion of patients who are alive at 12 months: number of patients alive at 12 months divided by the number of patients included initially; patients lost to follow up at 12 months will not be included in this analysis and those lost to follow up will be censured at the date of last news.
3. Duration of treatment with avelumab defined as the time between starting avelumab and permanently stopping avelumab regardless of cause. Patients still on treatment with avelumab at the date the data are frozen will be censured
4. Assessment of DFS and OS of avelumab in patients with a PD-L1 positive tumour. The definition of DFS and OS is the same and the analyses will be performed with the various positivity thresholds for PD-L1. DAKO/AGILENT clone IHC 22C3 will be the clone chosen
5. The overall safety profile of avelumab will be described from the assessment of toxicity following the CTCAE (Common Terminology Criteria for Adverse Events) criteria, version 4.03.
6. The times to the 1st and 2nd subsequent systemic therapy (TJPTSU; TJDTSU) are defined as the time period between the avelumab start date and the date of starting the 1st or 2nd anticancer treatment administered for SPC after failure of avelumab therapy. Patients who did not receive any subsequent treatment or who have died prior to receiving subsequent treatment will be censured.
7. Duration of administration of the first/subsequent systemic treatment defined as the time interval between starting the first/subsequent systemic therapy and permanently stopping this therapy regardless of cause. Patients still on treatment with first/subsequent systemic therapy at the date the data are frozen will be censured.
8. QoL will be assessed from the EORTC QLQ-C30 and EUROQOL EQ-5D questionnaires at baseline, D1 of each cycle (approximately 4 weeks), on leaving the study and on disease progression (if the study leaving date and date of progression differ by more than 4 weeks).
9. Survival without deterioration in quality of life (QFS) assessed from the QLQ-C30 questionnaire defined as the time interval between the date of inclusion and first minimum clinically significant difference (MCSD) in the score at inclusion without significant clinical improvement subsequently or death, regardless of cause.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire

Sponsor organisation

Centre Hospitalier Regional Universitaire

Address

2 Place Saint Jacques, Cs 51804 Cs 51804

City

Besancon Cedex

Postcode

25030

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Universitaire

Contact name

Guillaume MOUILLET

Public contact point

Organisation

Centre Hospitalier Regional Universitaire

Contact name

Elise ROBERT

Locations

1 EU/EEA country · 4 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 6 files

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

Application history

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