search
Back to results

Study of PembrolizumAb combiNeD With Cisplatin or carbOplatin and Etoposide in Treatment naïve Advanced meRkel Cell cArcinoma (MCC) (PANDORA)

Primary Purpose

Merkel Cell Carcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Pembrolizumab, Etoposide, Cisplatin or Carboplatin
Sponsored by
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Merkel Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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) Exclusion Criteria: 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. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Has had an allogenic tissue/solid organ transplant.

Sites / Locations

  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • AOUS Policlinico Le Scotte
  • Azienda Ospedaliera Universitaria Integrata (AOUI)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Incidence of Serius Adverse Events (SAE)
To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Incidence and severity of Adverse Events (AEs) according to NCI Common Terminology criteria Adverse Event (CTCAE), version 5.0
To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Incidence and severity of Immune-mediated Adverse Events (imAE)
To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Overall Survival (OS) that will be measured from the date of starting therapy to the date of death by any cause
To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Progression Free Survival (PFS) that will be measured from the date of starting therapy to the date of disease progression or death.
To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Duration of Response (DOR) that will be measured from the date of the first response to disease progression or death in those patients who achieved a CR o PR during study treatment.

Full Information

First Posted
September 26, 2023
Last Updated
October 10, 2023
Sponsor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
search

1. Study Identification

Unique Protocol Identification Number
NCT06086288
Brief Title
Study of PembrolizumAb combiNeD With Cisplatin or carbOplatin and Etoposide in Treatment naïve Advanced meRkel Cell cArcinoma (MCC)
Acronym
PANDORA
Official Title
Phase II, Open Label, Single Arm Study of PembrolizumAb combiNeD With Cisplatin or carbOplatin and Etoposide in Treatment naïve Advanced meRkel Cell cArcinoma (MCC) (PANDORA Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
December 2027 (Anticipated)
Study Completion Date
December 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Merkel Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single Arm
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab, Etoposide, Cisplatin or Carboplatin
Intervention Description
Induction Phase (4 cycles, 1Cycle=3W): Pembrolizumab 200 mg + Etoposide + Cisplatin or Carboplatin; Maintenance Phase (16 Cycles, 1Cycle=6W): Pembrolizumab 400 mg
Primary Outcome Measure Information:
Title
To assess the safety and antitumor activity of pembrolizumab combined with cisplatin/carboplatin and etoposide as first line treatment in MCC.
Description
ORR, that will be defined as the percentage of patients achieving complete response (CR) or partial response (PR) according to RECIST 1.1 criteria
Time Frame
48 months
Secondary Outcome Measure Information:
Title
To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Description
Incidence of Serius Adverse Events (SAE)
Time Frame
48 months
Title
To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Description
Incidence and severity of Adverse Events (AEs) according to NCI Common Terminology criteria Adverse Event (CTCAE), version 5.0
Time Frame
48 months
Title
To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Description
Incidence and severity of Immune-mediated Adverse Events (imAE)
Time Frame
48 months
Title
To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Description
Overall Survival (OS) that will be measured from the date of starting therapy to the date of death by any cause
Time Frame
48 months
Title
To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Description
Progression Free Survival (PFS) that will be measured from the date of starting therapy to the date of disease progression or death.
Time Frame
48 months
Title
To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
Description
Duration of Response (DOR) that will be measured from the date of the first response to disease progression or death in those patients who achieved a CR o PR during study treatment.
Time Frame
48 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) Exclusion Criteria: 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. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Has had an allogenic tissue/solid organ transplant.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sara Pusceddu
Phone
+390223903251
Email
sara.pusceddu@istitutotumori.mi.it
First Name & Middle Initial & Last Name or Official Title & Degree
Elvira Rostanzo
Phone
+390223902415
Email
elvira.rostanzo@istitutotumori.mi.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sara Pusceddu, MD
Organizational Affiliation
Fondazione IRCCS Istituto Nazionale Tumori Milano
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sara Pusceddu, MD
Phone
+390223903066
Email
sara.pusceddu@istitutotumori.mi.it
First Name & Middle Initial & Last Name & Degree
Maria Libera La Porta
Phone
+390223903892
Email
maria.laporta@istitutotumori.mi.it
First Name & Middle Initial & Last Name & Degree
Sara Pusceddu, MD
Facility Name
AOUS Policlinico Le Scotte
City
Siena
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Maria Di Giacomo
Email
annamaria.digiacomo@unisi.it
First Name & Middle Initial & Last Name & Degree
Anna Maria Di Giacomo, MD
Facility Name
Azienda Ospedaliera Universitaria Integrata (AOUI)
City
Verona
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sara Cingarlini
Email
sara.cingarlini@aovr.veneto.it
First Name & Middle Initial & Last Name & Degree
Sara Cingarlini, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of PembrolizumAb combiNeD With Cisplatin or carbOplatin and Etoposide in Treatment naïve Advanced meRkel Cell cArcinoma (MCC)

We'll reach out to this number within 24 hrs