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Efficacy of Immunotherapy Plus a Drug in Patients With Progressive Advanced Mucosal Cancer of Different Locations (PEVOsq)

Primary Purpose

Squamous Cell Lung Cancer, Vulvar Cancer, Penile Cancer

Status
Active
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
pembrolizumab; vorinostat
Sponsored by
UNICANCER
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Squamous Cell Lung Cancer focused on measuring squamous cell carcinoma, squamous cell cancer

Eligibility Criteria

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

Inclusion Criteria:

  1. Aged ≥18 years old.
  2. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
  3. Patients must have histologically confirmed recurrent and/or metastatic squamous cell carcinoma of the head and neck, cervix, lung, anus, vulva, or penis.
  4. Patients must have radiologically confirmed progressive recurrent and/or metastatic disease.
  5. Patients naive or previously treated for recurrent and/or metastatic disease for which a treatment with an anti-PD1/PD-L1 agents and vorinostat is an acceptable option according to investigator.
  6. Disease amenable to biopsy for study purpose.
  7. Measurable disease according to RECIST v1.1.
  8. Adequate renal function: serum creatinine ≤1.5 x upper limit of normal (ULN) (OR creatinine clearance [Cockcroft and Gault] ≥30 mL/min for participant with creatinine levels >1.5 × ULN) within 14 days prior inclusion.
  9. Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤3 × ULN (≤5 ULN when documented liver metastases) and total bilirubin level ≤1.5 × ULN, within 14 days prior inclusion.
  10. Adequate bone marrow function: absolute neutrophil count (ANC) ≥1,000/mm³, platelet count ≥100,000/mm³, and hemoglobin ≥9 g/dL, within 14 days prior inclusion.
  11. Adequate coagulation: prothrombin time (PT)/international normalized ratio (INR) ≤1.5 × ULN within 14 days prior inclusion If participant is receiving anticoagulant therapy then the PT or activated partial thromboplastin time (aPTT) should be within the therapeutic range of intended use of anticoagulant.
  12. Female of child-bearing potential must have a negative serum pregnancy test within 72 h before starting study treatment.
  13. Female of childbearing potential, must use "highly effective" methods of contraception for the study duration and for 4 months following the last dose of pembrolizumab and 6 months following the last dose of vorinostat.
  14. Male participants must agree to use an effective contraceptive for the duration of the trial and for at least 4 months after the last the last dose of pembrolizumab and 6 months following the last dose of vorinostat (to allow for effective elimination of the study drugs). Also, they should refrain from donating sperm during this period.
  15. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, and laboratory tests.
  16. Patients must be willing and able to comply with other study procedures, including a baseline tumor biopsy and a series of blood samples throughout the study.
  17. Patients able to swallow oral medications.
  18. Patients must be affiliated to a Social Security System (or equivalent).
  19. Patients must have signed a written informed consent prior to any trial-specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.

Exclusion Criteria:

  1. Prior treatment with anti-PD-1/PD-L1 agents or histone deacetylases (HDAC) inhibitors.
  2. Patients with central nervous system involvement that has not been controlled for >3 months.
  3. Patients with no other site for biopsy than bone lesions.
  4. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes, cardiac disease, uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infection within one year, chronic liver or renal disease, active gastrointestinal tract ulceration, severely impaired lung function.
  5. Known history of human immunodeficiency virus (HIV), Hepatitis B virus (HBV; defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (HCV; defined as HCV RNA detected) virus infection.
  6. History of autoimmune disease with the exception of:

    • (1) Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone,
    • (2) Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen,
    • (3) Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) provided that they meet the following conditions: (i) Rash must cover less than 10% of body surface area; (ii) Disease is well controlled at baseline and only requiring low potency topical steroids; (iii) No acute exacerbations of underlying condition within the previous 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoid, biologic agents, oral calcineurin inhibitors, high-potency or oral steroids).
  7. History of allogeneic organ or bone marrow transplantation.
  8. History of non-infectious pneumonitis that required steroids or has current pneumonitis.
  9. Has an active infection requiring systemic therapy.
  10. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
  11. Known prior severe hypersensitivity to investigational products or its excipients,
  12. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to first dose of study treatments.

    Note: Participants must have recovered from all adverse events due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.

  13. Has received prior radiotherapy within 2 weeks of start of study treatment. 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-central nervous system disease.
  14. Major surgery within 28 days prior to the first dose of study treatments. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  15. Current or prior use of immunosuppressive medication within 7 days before the first dose of pembrolizumab. The following are exceptions to this criterion:

    • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection),
    • Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or its equivalent,
    • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  16. Patients using drugs that could have pharmacokinetics interaction with investigational drugs. This includes, but is not limited to, valproic acid, coumarin-derivative anticoagulants, drugs that disrupt electrolyte levels, drugs that may prolong QT.
  17. Pregnant women or women who are breast-feeding.
  18. Patients enrolled in another therapeutic study within 30 days prior to inclusion and during the treatment period. Patients can participate in an independent approved non-interventional studies.
  19. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
  20. Persons deprived of their liberty or under protective custody or guardianship

Sites / Locations

  • Institut de Cancérologie de l'Ouest - Site Paul Papin
  • Institut Bergonié
  • Centre François Baclesse
  • Centre Jean Perrin
  • Centre George François Leclerc
  • Centre Oscar Lambret
  • Centre Léon Bérard
  • Institut de Cancérologie de Lorraine
  • Institut de Cancérologie de l'Ouest (site René Gauducheau)
  • Institut Curie
  • Centre Hospitalier Lyon Sud - Hospices Civils de Lyon
  • Institut Godinot
  • Centre Paul Strauss
  • Institut Claudius Regaud

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

pembrolizumab + vorinostat

Arm Description

Pembrolizumab: 200 mg every 3 weeks, up to 35 administrations Vorinostat: 400 mg once daily, until progression

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR), investigator assessment
Investigators will assess the ORR. The ORR is defined in each cohort as the percentage of evaluable patients for ORR, designate as the proportion of patients with best response of complete response (CR) or a partial response (PR) during treatment according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1).

Secondary Outcome Measures

Objective Response Rate (ORR), central assessment
ORR defined as the proportion of patients with best response of CR or PR during treatment, as assessed by a central radiological panel according to RECIST v1.1.
immune Objective Response Rate (iORR), central assessment
ORR defined as the proportion of patients with best response of CR or PR during treatment, as assessed by a central radiological panel according to immune-specific response criteria.
Duration Of Response (DOR)
DOR will be evaluated in patients with either CR or PR. DOR is defined as the time from the first assessment of a CR or PR until the date of the first occurrence of progressive disease (PD) or death from any cause (if death occurred within predefined period), whichever occurs first.
Progression Free Survival (PFS)
PFS is defined per RECIST v1.1 as the time from inclusion until disease progression (per RECIST v1.1) or death from any cause, whichever occurs first. At the time of analysis, a patient alive and without disease progression will be censored at the date of the last tumor assessment. Patients alive without disease progression who started a new anticancer therapy will be censored at the date of the last tumor assessment prior to the start of the new anticancer therapy.
immune Progression Free Survival (iPFS)
iPFS is defined per immune-specific response evaluation criteria in solid tumors (iRECIST) as the time from inclusion until confirmed disease progression (per iRECIST), or death from any cause, whichever occurs first. At the time of analysis, a patient alive and without progression will be censored at the date of the last tumor assessment. Patients alive without disease progression who started a new anti-cancer therapy will be censored at the date of the last tumor assessment prior to the start of the new anticancer therapy.
Overall Survival (OS)
OS is defined as the time from inclusion until death from any cause. Patients who are alive at last follow-up news will be censored at this date.

Full Information

First Posted
April 20, 2020
Last Updated
January 4, 2023
Sponsor
UNICANCER
Collaborators
Merck Sharp & Dohme LLC, Fondation ARC, ERA-NET
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1. Study Identification

Unique Protocol Identification Number
NCT04357873
Brief Title
Efficacy of Immunotherapy Plus a Drug in Patients With Progressive Advanced Mucosal Cancer of Different Locations
Acronym
PEVOsq
Official Title
Phase II Basket Trial Evaluating the Efficacy of a Combination of Pembrolizumab and Vorinostat in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 28, 2020 (Actual)
Primary Completion Date
December 15, 2022 (Actual)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNICANCER
Collaborators
Merck Sharp & Dohme LLC, Fondation ARC, ERA-NET

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Interventional study evaluating the efficacy of an immunotherapy (pembrolizumab) in combination with a targeted therapy (vorinostat) in patient with recurrent and/or metastatic squamous cell carcinoma (localisations : head and neck, lung, cervix, anus, vulva, and penis)
Detailed Description
Open-label, non-randomized, multi-center, basket phase II trial, evaluating the efficacy of pembrolizumab in combination with vorinostat in adult patients with recurrent and/or metastatic squamous cell carcinoma of different locations. Antitumor activity of the combination will be evaluated using the objective response rate (ORR) during treatment (investigator assessment).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Lung Cancer, Vulvar Cancer, Penile Cancer, Cervix Cancer, Head and Neck Squamous Cell Carcinoma, Anal Cancer
Keywords
squamous cell carcinoma, squamous cell cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
6 independent cohorts (head and neck, cervix, lung, anus, vulva, and penis) evaluating the association of pembrolizumab and vorinostat
Masking
None (Open Label)
Allocation
N/A
Enrollment
112 (Actual)

8. Arms, Groups, and Interventions

Arm Title
pembrolizumab + vorinostat
Arm Type
Experimental
Arm Description
Pembrolizumab: 200 mg every 3 weeks, up to 35 administrations Vorinostat: 400 mg once daily, until progression
Intervention Type
Drug
Intervention Name(s)
pembrolizumab; vorinostat
Other Intervention Name(s)
KEYTRUDA; ZOLINZA
Intervention Description
Pembrolizumab: 200 mg every 3 weeks, up to 35 administrations Vorinostat: 400 mg once daily, until progression
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR), investigator assessment
Description
Investigators will assess the ORR. The ORR is defined in each cohort as the percentage of evaluable patients for ORR, designate as the proportion of patients with best response of complete response (CR) or a partial response (PR) during treatment according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1).
Time Frame
From inclusion to first and subsequent tumor assesment or progression, up to 24 months
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR), central assessment
Description
ORR defined as the proportion of patients with best response of CR or PR during treatment, as assessed by a central radiological panel according to RECIST v1.1.
Time Frame
From inclusion to first and subsequent tumor assesment or progression, up to 36 months
Title
immune Objective Response Rate (iORR), central assessment
Description
ORR defined as the proportion of patients with best response of CR or PR during treatment, as assessed by a central radiological panel according to immune-specific response criteria.
Time Frame
From inclusion to first and subsequent tumor assesment or progression, up to 36 months
Title
Duration Of Response (DOR)
Description
DOR will be evaluated in patients with either CR or PR. DOR is defined as the time from the first assessment of a CR or PR until the date of the first occurrence of progressive disease (PD) or death from any cause (if death occurred within predefined period), whichever occurs first.
Time Frame
From the first assessment of a CR or PR until the date of the first occurrence of PD or death from any cause
Title
Progression Free Survival (PFS)
Description
PFS is defined per RECIST v1.1 as the time from inclusion until disease progression (per RECIST v1.1) or death from any cause, whichever occurs first. At the time of analysis, a patient alive and without disease progression will be censored at the date of the last tumor assessment. Patients alive without disease progression who started a new anticancer therapy will be censored at the date of the last tumor assessment prior to the start of the new anticancer therapy.
Time Frame
From inclusion to disease progression or death, up to 36 months
Title
immune Progression Free Survival (iPFS)
Description
iPFS is defined per immune-specific response evaluation criteria in solid tumors (iRECIST) as the time from inclusion until confirmed disease progression (per iRECIST), or death from any cause, whichever occurs first. At the time of analysis, a patient alive and without progression will be censored at the date of the last tumor assessment. Patients alive without disease progression who started a new anti-cancer therapy will be censored at the date of the last tumor assessment prior to the start of the new anticancer therapy.
Time Frame
From inclusion to disease progression or death, up to 36 months
Title
Overall Survival (OS)
Description
OS is defined as the time from inclusion until death from any cause. Patients who are alive at last follow-up news will be censored at this date.
Time Frame
From inclusion to death from any cause, up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged ≥18 years old. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Patients must have histologically confirmed recurrent and/or metastatic squamous cell carcinoma of the head and neck, cervix, lung, anus, vulva, or penis. Patients must have radiologically confirmed progressive recurrent and/or metastatic disease. Patients naive or previously treated for recurrent and/or metastatic disease for which a treatment with an anti-PD1/PD-L1 agents and vorinostat is an acceptable option according to investigator. Disease amenable to biopsy for study purpose. Measurable disease according to RECIST v1.1. Adequate renal function: serum creatinine ≤1.5 x upper limit of normal (ULN) (OR creatinine clearance [Cockcroft and Gault] ≥30 mL/min for participant with creatinine levels >1.5 × ULN) within 14 days prior inclusion. Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤3 × ULN (≤5 ULN when documented liver metastases) and total bilirubin level ≤1.5 × ULN, within 14 days prior inclusion. Adequate bone marrow function: absolute neutrophil count (ANC) ≥1,000/mm³, platelet count ≥100,000/mm³, and hemoglobin ≥9 g/dL, within 14 days prior inclusion. Adequate coagulation: prothrombin time (PT)/international normalized ratio (INR) ≤1.5 × ULN within 14 days prior inclusion If participant is receiving anticoagulant therapy then the PT or activated partial thromboplastin time (aPTT) should be within the therapeutic range of intended use of anticoagulant. Female of child-bearing potential must have a negative serum pregnancy test within 72 h before starting study treatment. Female of childbearing potential, must use "highly effective" methods of contraception for the study duration and for 4 months following the last dose of pembrolizumab and 6 months following the last dose of vorinostat. Male participants must agree to use an effective contraceptive for the duration of the trial and for at least 4 months after the last the last dose of pembrolizumab and 6 months following the last dose of vorinostat (to allow for effective elimination of the study drugs). Also, they should refrain from donating sperm during this period. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, and laboratory tests. Patients must be willing and able to comply with other study procedures, including a baseline tumor biopsy and a series of blood samples throughout the study. Patients able to swallow oral medications. Patients must be affiliated to a Social Security System (or equivalent). Patients must have signed a written informed consent prior to any trial-specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent. Exclusion Criteria: Prior treatment with anti-PD-1/PD-L1 agents or histone deacetylases (HDAC) inhibitors. Patients with central nervous system involvement that has not been controlled for >3 months. Patients with no other site for biopsy than bone lesions. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes, cardiac disease, uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infection within one year, chronic liver or renal disease, active gastrointestinal tract ulceration, severely impaired lung function. Known history of human immunodeficiency virus (HIV), Hepatitis B virus (HBV; defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (HCV; defined as HCV RNA detected) virus infection. History of autoimmune disease with the exception of: (1) Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone, (2) Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen, (3) Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) provided that they meet the following conditions: (i) Rash must cover less than 10% of body surface area; (ii) Disease is well controlled at baseline and only requiring low potency topical steroids; (iii) No acute exacerbations of underlying condition within the previous 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoid, biologic agents, oral calcineurin inhibitors, high-potency or oral steroids). History of allogeneic organ or bone marrow transplantation. History of non-infectious pneumonitis that required steroids or has current pneumonitis. Has an active infection requiring systemic therapy. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Known prior severe hypersensitivity to investigational products or its excipients, Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to first dose of study treatments. Note: Participants must have recovered from all adverse events due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Has received prior radiotherapy within 2 weeks of start of study treatment. 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-central nervous system disease. Major surgery within 28 days prior to the first dose of study treatments. Note: Local surgery of isolated lesions for palliative intent is acceptable. Current or prior use of immunosuppressive medication within 7 days before the first dose of pembrolizumab. The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or its equivalent, Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). Patients using drugs that could have pharmacokinetics interaction with investigational drugs. This includes, but is not limited to, valproic acid, coumarin-derivative anticoagulants, drugs that disrupt electrolyte levels, drugs that may prolong QT. Pregnant women or women who are breast-feeding. Patients enrolled in another therapeutic study within 30 days prior to inclusion and during the treatment period. Patients can participate in an independent approved non-interventional studies. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons. Persons deprived of their liberty or under protective custody or guardianship
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christophe Le Tourneau, MD
Organizational Affiliation
Institut Curie
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut de Cancérologie de l'Ouest - Site Paul Papin
City
Angers
Country
France
Facility Name
Institut Bergonié
City
Bordeaux
Country
France
Facility Name
Centre François Baclesse
City
Caen
Country
France
Facility Name
Centre Jean Perrin
City
Clermont-Ferrand
Country
France
Facility Name
Centre George François Leclerc
City
Dijon
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
Country
France
Facility Name
Centre Léon Bérard
City
Lyon
Country
France
Facility Name
Institut de Cancérologie de Lorraine
City
Nancy
Country
France
Facility Name
Institut de Cancérologie de l'Ouest (site René Gauducheau)
City
Nantes
Country
France
Facility Name
Institut Curie
City
Paris
Country
France
Facility Name
Centre Hospitalier Lyon Sud - Hospices Civils de Lyon
City
Pierre-Bénite
Country
France
Facility Name
Institut Godinot
City
Reims
Country
France
Facility Name
Centre Paul Strauss
City
Strasbourg
Country
France
Facility Name
Institut Claudius Regaud
City
Toulouse
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

Learn more about this trial

Efficacy of Immunotherapy Plus a Drug in Patients With Progressive Advanced Mucosal Cancer of Different Locations

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