This is a single-arm phase 2 clinical trial involving women with unresectable, incompletely
resected, recurrent, or metastatic vulva squamous cell carcinoma. This study combines
cisplatin, pembrolizumab, and radiation therapy to see if this combination further increases
participants' immune system's efficiency in killing their tumor, and if the combination
decreases the chances of participants' cancer coming back.
The research study procedures include screening for eligibility and study treatment including
evaluations and follow up visits.
This research study involves the following:
- Cisplatin (standard of care drug)
- Pembrolizumab (investigational drug)
- Radiation Therapy (standard of care intervention)
Participants will receive study treatment for up to 36 weeks and will be followed for up to 3
It is expected that about 24 people will take part in this research study.
Phase II clinical trials test the safety and effectiveness of an investigational drug to
learn whether the drug works in treating a specific disease. "Investigational" means that the
drug is being studied. The U.S. Food and Drug Administration (FDA) has approved cisplatin as
a treatment option for vulva squamous cell carcinoma. The FDA has not approved pembrolizumab
for vulva squamous cell carcinoma, but it has been approved for other uses. Cisplatin is a
chemotherapy drug and will be given to participants per standard of care.
Radiation therapy will be given to you per standard of care. Pembrolizumab is a drug that may
target participants immune systems to increase its efficiency in targeting and killing
illnesses and diseases, such as unresectable vulvar squamous cell carcinoma.
- Participants must have histologically or cytologically confirmed unresectable,
incompletely resected, recurrent, or metastatic squamous cell carcinoma of the
vulva.Patients with unresectable disease are defined as T2 or T3 primary tumors (N0-3,
M0) not amenable to surgical resection by standard radical vulvectomy.
- Participants must 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.
- Prior therapy: Participants with no prior therapy are eligible and patients with
recurrent disease must not have had more than two lines of cytotoxic therapy. Topical
or hormonal therapy are not counted towards prior lines. Prior treatment with
immunotherapy is allowed, provided treatment was not stopped for grade 2 or greater
- Time from prior therapy:
- Systemic anti-neoplastic therapy: 5 half-lives or 4 weeks, whichever is shorter.
- Hormonal therapy is not considered anti-neoplastic therapy.
- Radiotherapy: Any prior irradiation is acceptable provided the site being
considered for study has not been previously irradiated.
- Age ≥18 years. Because insufficient dosing or adverse event data are currently
available on the use of pembrolizumab in combination with cisplatin-sensitized
radiation therapy participants <18 years of age, children are excluded. Vulva cancer
is rare in the pediatric population
- ECOG performance status of 0 or 1.
- Participants must have adequate organ and marrow function as defined below (Table 1):
- Table 1: Adequate Organ Function Laboratory Values
- Absolute neutrophil count (ANC) ≥1500/μL
- Platelets ≥100 000/μL
- Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
- Creatinine OR Measured or calculated b creatinine clearance (GFR can
also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥50 mL/min
for participant with creatinine
- Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants
with total bilirubin levels >1.5 × ULN
- AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with
- International normalized ratio (INR) OR prothrombin time (PT) Activated
partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is
receiving anticoagulant therapy as long as PT or aPTT is within
therapeutic range of intended use of anticoagulants
- ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic
transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic
oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper
limit of normal.
- Criteria must be met without erythropoietin dependency and without
packed red blood cell (pRBC) transfusion within last 2 weeks.
- Creatinine clearance (CrCl) should be calculated per institutional
- Note: This table includes eligibility-defining laboratory value
requirements for treatment; laboratory value requirements should be
adapted according to local regulations and guidelines for the
administration of specific chemotherapies.
- Participant must be female, and is eligible to participate if she is not pregnant (see
Appendix B), not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix B OR
- A WOCBP must agree to use adequate contraception (hormonal or barrier method of
birth control; abstinence) prior to study entry, during study treatment, and for
at least twelve weeks after the last dose of study treatment. Should a woman
become pregnant or suspect she is pregnant while she is pregnant while she is
participating in this study, she should inform her treating physician
- Ability to understand and the willingness to sign a written informed consent document.
- Patients who in the opinion of the investigator cannot safely receive a minimum of 30
Gy in 10 fractions are not eligible for the trial.
- Participants who have received prior systemic anti-cancer therapy including
investigational agents within 4 weeks prior to first dose of study treatment. Note: If
participant received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting study treatment
- Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or
- 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. Re-irradiation to a
previously treated site will not be permitted.
- Participants who have 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
- Participants with vulvar melanomas, sarcomas, extramammary Paget's disease, or basal
- Participants with a history of gastrointestinal or colovesicular fistulae
- 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.
- 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 treatment.
- Has a history of (non-infectious) pneumonitis that required steroids or has current
- Has an active infection requiring systemic therapy.
- Patients with a history of other invasive malignancies, with the exception of
nonmelanoma skin cancer, are excluded if there is any evidence of other malignancy
being present within the last five years. Patients are also excluded if their previous
cancer treatment contraindicates this protocol therapy.
- Participants with uncontrolled intercurrent illness.
- Participants with psychiatric illness/social situations that would limit compliance
with study requirements.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required.
- Has a known history of active TB (Bacillus Tuberculosis).
- Pregnant or nursing women are excluded from this study because effects of agents used
in this study on infants or the developing human fetus are unknown.
- Presence of other malignancies unless they are considered cured by patient's
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
- Has a known history of Human Immunodeficiency Virus (HIV).