Cisplatin+Pembrolizumab+RT in Vulvar Cancer

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Brief Title

Cisplatin+Pembrolizumab+RT in Vulvar Cancer

Official Title

A Phase 2 Study of Combined Chemo-immunotherapy With Cisplatin-pembrolizumab and Radiation for Unresectable Vulvar Squamous Cell Carcinoma

Brief Summary

      This research is being done to see how well the combination of a standard of care drug,
      investigational drug, and radiation therapy work against unresectable vulvar squamous cell
      carcinoma.

      This research study involves the following:

        -  Cisplatin (standard of care drug)

        -  Pembrolizumab (investigational drug)

        -  Radiation Therapy (standard of care intervention)
    

Detailed Description

      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
      years.

      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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall response rate (ORR)

Secondary Outcome

 Recurrence Free Survival (RFS)-6 months

Condition

Vulvar Cancer

Intervention

Cisplatin

Study Arms / Comparison Groups

 Pembrolizumab, Cisplatin and Radiation Therapy
Description:  Treatment period is 36 weeks with 21 day study cycles.
Participants will receive cisplatin at a predetermined dose 1x weekly, pembrolizumab at a predetermined dose every 3 weeks, concurrently with daily radiation therapy from week 1 up to week 8.
First 3 participants on the study, may skip 1 or 2 pembrolizumab dosages while receiving radiation therapy.
Following completion of daily radiation therapy with 1x weekly cisplatin and 1x every 3 weeks pembrolizumab, participants will continue at a pre-determined maintenance dose of pembrolizumab 1x every 3 weeks for a total of 12 cycles or 36 weeks.

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

24

Start Date

July 29, 2020

Completion Date

January 30, 2025

Primary Completion Date

December 30, 2022

Eligibility Criteria

        Inclusion Criteria:

          -  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
             adverse events.

          -  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

                    -  Hematological

                         -  Absolute neutrophil count (ANC) ≥1500/μL

                         -  Platelets ≥100 000/μL

                         -  Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La

                    -  Renal

                         -  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

                    -  Hepatic

                         -  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
                            liver metastases)

                    -  Coagulation

                         -  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
                            standard.

                         -  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
                  immediately.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  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
             baseline.

          -  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
             allowed.

          -  Participants with vulvar melanomas, sarcomas, extramammary Paget's disease, or basal
             cell carcinoma

          -  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
             pneumonitis.

          -  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
             oncologist.

          -  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).
      

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Oladapo Yeku, MD, PHD, 617-643-9354, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04430699

Organization ID

20-109


Responsible Party

Principal Investigator

Study Sponsor

Massachusetts General Hospital

Collaborators

 Merck Sharp & Dohme Corp.

Study Sponsor

Oladapo Yeku, MD, PHD, Principal Investigator, Massachusetts General Hospital


Verification Date

January 2021