Clinical Trials /

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

NCT03774901

Description:

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.

Related Conditions:
  • Squamous Cell Carcinoma of the Penis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: P/2017/337
  • SECONDARY ID: 2018-001427-38
  • NCT ID: NCT03774901

Conditions

  • Penile Cancer
  • Penile Neoplasms
  • Penile Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
Avelumabavelumab maintenance

Purpose

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.

Trial Arms

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

Eligibility Criteria

        Key Eligibility Criteria

        Inclusion:

          -  Histologically confirmed unresectable locally advanced or metastatic squamous cell
             penile carcinoma

          -  Patients who have received a minimum of 3 and a maximum of 6 cycles of
             polychemotherapy including a platinum (cisplatin or carboplatin) administered as 1st
             line systemic treatment.

        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

          -  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.

          -  ECOG (Eastern Cooperative Group) performance status of 0 to 2

          -  Adequate organ function:

        Absolute neutrophil (N) count ≥ 1500/mm3 ou ≥ 1,5.10^9/L Platelets ≥ 100 000 / mm3
        Haemoglobin ≥ 9 g/dL Creatinine clearance ≥ 30 mL/min (by the MDRD formula) Total bilirubin
        ≤ 1.5 x ULN (upper limit of the normal range) AST ≤ 2.5 x ULN and ALT ≤ 2.5 x ULN OR AST
        and ALT ≤ 5 x ULN if liver abnormalities due to liver metastases AST = aspartate
        aminotransferase ALT = alanine aminotransferase

        Exclusion:

          -  Patients who have never received chemotherapy with a platinum (cisplatin or
             carboplatin)

          -  Patients who have received more than one previous line of systemic treatment for
             penile cancer unless in case of more than 12 months delay between the end of prior
             treatment and the start of platinum containing polychemotherapy required.

          -  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

          -  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

          -  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

          -  Patients with a past history of known central nervous system metastases, meningeal
             carcinomatosis or spinal compression

          -  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)

          -  Active autoimmune 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

          -  Patients with uncontrolled adrenal failure

          -  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.

          -  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)

          -  Active infection requiring systemic treatment

          -  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).

          -  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

          -  Previous organ transplant including stem cell allotransplantation

          -  Any screening test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating
             active infection

          -  Vaccination within 4 weeks prior to first administration of avelumab and throughout
             the period of the study, except with inactivated vaccines (such as, inactivated
             influenza vaccines).

          -  Men of childbearing 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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:PFS (progression-free survival)
Time Frame:24 months
Safety Issue:
Description:To estimate progression-free survival in patients included in this study

Secondary Outcome Measures

Measure:OS (overall survival)
Time Frame:32 months
Safety Issue:
Description:To estimate overall survival in patients included in this study
Measure:MDT (median duration of treatment)
Time Frame:24 months
Safety Issue:
Description:To estimate the median duration of avelumab treatment calculated from avelumab initiation in patients included in this study
Measure:QOL (quality of life) assessed by EORTC QLQ-C30
Time Frame:24 months
Safety Issue:
Description:To assess health-related quality of life since avelumab is started in patients included in this study
Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time Frame:24 months
Safety Issue:
Description:To assess safety profile after avelumab initiation

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Centre Hospitalier Universitaire de Besancon

Trial Keywords

  • Immunotherapy
  • Penile Cancer
  • Penile Squamous Cell Carcinoma
  • Avelumab
  • maintenance

Last Updated

November 15, 2019