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

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Brief Title

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

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

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).
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Objective Response Rate (ORR), investigator assessment

Secondary Outcome

 Objective Response Rate (ORR), central assessment

Condition

Squamous Cell Lung Cancer

Intervention

pembrolizumab; vorinostat

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

111

Start Date

October 28, 2020

Completion Date

October 2024

Primary Completion Date

October 28, 2022

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Christophe Le Tourneau, MD, 017379732, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT04357873

Organization ID

UC-GMP-1908

Secondary IDs

2019-003839-33

Responsible Party

Sponsor

Study Sponsor

UNICANCER

Collaborators

 Merck Sharp & Dohme Corp.

Study Sponsor

Christophe Le Tourneau, MD, Principal Investigator, Institut Curie


Verification Date

June 2021