| Eligibility |
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
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