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

NCT04357873 | Completed Phase 2 DMC

• 2 other identifiers: UC-GMP-19082019-003839-33
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 14

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)

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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).

  From inclusion to first and subsequent tumor assesment or progression, up to 24 months

Secondary Outcomes (6)

• Objective Response Rate (ORR), central assessment

  From inclusion to first and subsequent tumor assesment or progression, up to 36 months

• immune Objective Response Rate (iORR), central assessment

  From inclusion to first and subsequent tumor assesment or progression, up to 36 months

• Duration Of Response (DOR)

  From the first assessment of a CR or PR until the date of the first occurrence of PD or death from any cause

• Progression Free Survival (PFS)

  From inclusion to disease progression or death, up to 36 months

• immune Progression Free Survival (iPFS)

  From inclusion to disease progression or death, up to 36 months

Study Arms (1)

pembrolizumab + vorinostat

EXPERIMENTAL

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

Drug: pembrolizumab; vorinostat

Interventions

pembrolizumab; vorinostat DRUG

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

Also known as: KEYTRUDA; ZOLINZA

pembrolizumab + vorinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• UNICANCER: lead
• Merck Sharp & Dohme LLC: collaborator
• Fondation ARC: collaborator
• ERA-NET: collaborator

Study Sites (14)

Institut de Cancérologie de l'Ouest - Site Paul Papin

Angers, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Centre George François Leclerc

Dijon, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut de Cancérologie de Lorraine

Nancy, France

Location

Institut de Cancérologie de l'Ouest (site René Gauducheau)

Nantes, France

Location

Institut Curie

Paris, France

Location

Centre Hospitalier Lyon Sud - Hospices Civils de Lyon

Pierre-Bénite, France

Location

Institut Godinot

Reims, France

Location

Centre Paul Strauss

Strasbourg, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Related Publications (2)

• Filippini DM, Cabarrou B, Dupain C, Halladjian M, Coquan E, Sablin MP, Mazzarella L, Francisco M, Servant N, Tonini MM, Hundt AF, Castel-Ajgal Z, You B, Bigot F, Ghiringhelli F, Vansteene D, Gomez-Roca C, Cousin S, Lambert A, Saada-Bouzid E, Durando X, Abdeddaim C, Borel C, Chaltiel R, Borcoman E, Legrand F, Bernhart S, Jimenez M, Bieche I, Filleron T, Le Tourneau C, Kamal M, Jeannot E. HPV circulating tumor DNA to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous-cell carcinomas. ESMO Open. 2026 Jan;11(1):106024. doi: 10.1016/j.esmoop.2025.106024. Epub 2025 Dec 29.

  PMID: 41468684 DERIVED

• Borcoman E, Cabarrou B, Francisco M, Bigot F, Ghiringhelli F, Vansteene D, Legrand F, Halladjian M, Dupain C, Le Saux O, Coutzac C, Borel C, Chaltiel R, You B, Gomez-Roca C, Cousin S, Coquan E, Lambert A, Saada-Bouzid E, Durando X, Saint-Ghislain M, Frige G, Guerini-Rocco E, Tonini MM, Bieche I, Castel-Ajgal Z, Marret G, Sablin MP, Jeannot E, Andre F, Filleron T, Jimenez M, Mazzarella L, Servant N, Kamal M, Le Tourneau C. Efficacy of pembrolizumab and vorinostat combination in patients with recurrent and/or metastatic squamous cell carcinomas: a phase 2 basket trial. Nat Cancer. 2025 Aug;6(8):1370-1383. doi: 10.1038/s43018-025-01004-2. Epub 2025 Jun 30.

  PMID: 40588522 DERIVED

MeSH Terms

Conditions

Vulvar Neoplasms; Penile Neoplasms; Uterine Cervical Neoplasms; Squamous Cell Carcinoma of Head and Neck; Anus Neoplasms; Carcinoma, Squamous Cell; Neoplasms, Squamous Cell

Interventions

pembrolizumab; Vorinostat

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Vulvar Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Penile Diseases; Male Urogenital Diseases; Uterine Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Christophe Le Tourneau, MD

  Institut Curie

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: 6 independent cohorts (head and neck, cervix, lung, anus, vulva, and penis) evaluating the association of pembrolizumab and vorinostat

Study Record Dates

• First Submitted: April 20, 2020
• First Posted: April 22, 2020
• Study Start: October 28, 2020
• Primary Completion: December 15, 2022
• Study Completion: November 26, 2024
• Last Updated: February 19, 2025

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (14)