NCT06086288

Brief Summary

This is an open label, multicenter, phase II study evaluating the activity and safety of pembrolizumab combined with cisplatin/carboplatin and etoposide as first line treatment in patients with advanced MCC.

Trial Health

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Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P25-P50 for phase_2

Timeline
18mo left

Started Nov 2023

Typical duration for phase_2

Geographic Reach
1 country

3 active sites

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress64%
Nov 2023Dec 2027

First Submitted

Initial submission to the registry

September 26, 2023

Completed
21 days until next milestone

First Posted

Study publicly available on registry

October 17, 2023

Completed
15 days until next milestone

Study Start

First participant enrolled

November 1, 2023

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2027

Last Updated

October 17, 2023

Status Verified

September 1, 2023

Enrollment Period

4.1 years

First QC Date

September 26, 2023

Last Update Submit

October 10, 2023

Conditions

Outcome Measures

Primary Outcomes (1)

  • To assess the safety and antitumor activity of pembrolizumab combined with cisplatin/carboplatin and etoposide as first line treatment in MCC.

    ORR, that will be defined as the percentage of patients achieving complete response (CR) or partial response (PR) according to RECIST 1.1 criteria

    48 months

Secondary Outcomes (6)

  • To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC

    48 months

  • To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC

    48 months

  • To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC

    48 months

  • To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC

    48 months

  • To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC

    48 months

  • +1 more secondary outcomes

Study Arms (1)

Single Arm

EXPERIMENTAL
Drug: Pembrolizumab, Etoposide, Cisplatin or Carboplatin

Interventions

Induction Phase (4 cycles, 1Cycle=3W): Pembrolizumab 200 mg + Etoposide + Cisplatin or Carboplatin; Maintenance Phase (16 Cycles, 1Cycle=6W): Pembrolizumab 400 mg

Single Arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male/female subjects with histologically confirmed diagnosis of MCC, who have not received prior systemic treatment for their advanced or metastatic MCC, are at least 18 years of age on the day of signing informed consent, will be enrolled in this study.
  • Male participants:
  • 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 120 days, corresponding to time needed to eliminate any study treatments (e.g. 5 terminal half-lives for pembrolizumab and/or any active comparator/combination) plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period.
  • Female participants:
  • A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
  • a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatments (pembrolizumab and/or any active comparator/combination) plus 30 days (a menstruation cycle) after the last dose of study treatment.
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
  • Unresectable and locally advanced, relapsed or metastatic MCC stage IIIB-IV according to American Joint Committee on Cancer (AJCC) TNM Staging Classification for Merkel Cell Carcinoma (8th ed. 2017)
  • No prior systemic treatment for metastic MCC. Subjects who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the onset of metastatic disease.
  • Have a life expectancy of at least 3 months.
  • Have measurable disease based on RECIST 1.1. 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 first dose of study intervention.
  • Have adequate organ function (protocol table 4)

You may not qualify if:

  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • 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.
  • Has received prior radiotherapy within 2 weeks of start of study intervention. 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 or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
  • 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 intervention.
  • 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 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
  • 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 and is allowed.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Has a known history of Human Immunodeficiency Virus (HIV) infection.
  • Has a known history of active Hepatitis B (defined as HBV DNA is detected) or known active Hepatitis C virus (defined as HCV RNA quantitative is detected) infection.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

AOUS Policlinico Le Scotte

Siena, Italy

Location

Azienda Ospedaliera Universitaria Integrata (AOUI)

Verona, Italy

Location

Related Publications (1)

  • Oldani S, Prinzi N, Morano F, Cingarlini S, Di Giacomo AM, Niger M, Prisciandaro M, Raimondi A, Randon G, Pircher CC, Borghesani M, Valente M, Rostanzo E, Milione M, Sabella G, Cascella T, Ghelardi F, Sciortino C, Gusmaroli E, Nasca V, de Braud F, Pietrantonio F, Pusceddu S. Design and rationale of the phase II PANDORA trial: first line chemo-immunotherapy in advanced Merkel cell carcinoma. Future Oncol. 2025 Jul;21(17):2127-2133. doi: 10.1080/14796694.2025.2514402. Epub 2025 Jun 12.

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

pembrolizumabEtoposideCisplatinCarboplatin

Condition Hierarchy (Ancestors)

Polyomavirus InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsCarcinoma, NeuroendocrineNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

PodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsGlucosidesGlycosidesCarbohydratesChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsCoordination Complexes

Study Officials

  • Sara Pusceddu, MD

    Fondazione IRCCS Istituto Nazionale Tumori Milano

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 26, 2023

First Posted

October 17, 2023

Study Start

November 1, 2023

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Last Updated

October 17, 2023

Record last verified: 2023-09

Data Sharing

IPD Sharing
Will not share

Locations