Pembrolizumab in Refractory Metastatic Anal Cancer

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Brief Title

Pembrolizumab in Metastatic Anal Cancer

Official Title

A Multicenter Phase 2 Clinical Trial of Pembrolizumab in Metastatic Anal Cancer

Brief Summary

      This research study is studying a targeted therapy as a possible treatment for advanced anal
      cancer.

      The following intervention will be involved in this study:

      -Pembrolizumab
    

Detailed Description

      This research study is a Phase II clinical trial. 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 FDA (the U.S. Food and Drug Administration) has not approved pembrolizumab for Advanced
      Anal Cancer, but it has been approved for other uses.

      Pembrolizumab, also known as KEYTRUDA or MK-3475, is approved in the USA and several other
      countries to treat a type of skin cancer called Malignant Melanoma.

      In this research study the investigators are studying an investigational drug called
      Pembrolizumab, which is a monoclonal antibody. Monoclonal antibodies are manmade and mimic
      proteins in the immune system by attaching to specific proteins in the body. T cells are
      cells in the immune system that are controlled by PD-1. PD-1 is a protein on the T cells that
      prevent the body from overproducing T cells. Pembrolizumab targets PD-1, attaches to it and
      blocks its action. By preventing PD-1 from working, T cell production rises and the body's
      immune system may increase its action against Cancer cells. Clinical and laboratory studies
      using pembrolizumab suggest that pembrolizumab may be useful in shrinking certain tumors.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall Response Rate

Secondary Outcome

 PD-L1 Positive Response Rate

Condition

Anal Cancer

Intervention

Pembrolizumab

Study Arms / Comparison Groups

 Pembrolizumab
Description:  Pembrolizumab is administered every 3 week intravenously
Dosage to be determine by physician

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

32

Start Date

October 11, 2016

Completion Date

March 2023

Primary Completion Date

March 2022

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have metastatic anal cancer that has been histologically confirmed.

          -  There is no limit to the number of prior therapies.

          -  Be willing and able to provide written informed consent/assent for the trial.

          -  Be ≥18 years of age on day of signing informed consent.

          -  Have measurable disease based on RECIST 1.1.

          -  Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
             prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples
             cannot be provided (e.g. inaccessible or subject safety concern) may submit an
             archived specimen only upon agreement from the Sponsor.

          -  Have a performance status of 0 or 1 on the ECOG Performance Scale.

          -  Demonstrate adequate organ function, all screening labs must be performed within 10
             days of treatment initiation.

        Adequate Organ Function Laboratory Values

        System Laboratory Value

          -  Hematological

               -  Absolute neutrophil count (ANC) ≥1,500 /mcL

               -  Platelets ≥80,000 / mcL

               -  Hemoglobin ≥8.5 g/dL or ≥5.6 mmol/L

          -  Renal

             --Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be
             used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min
             for subject with creatinine levels > 1.5 X institutional ULN

          -  Hepatic

               -  Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with
                  total bilirubin levels > 1.5 ULN

               -  AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver
                  metastases

               -  Albumin >2.8 mg/dL

          -  Coagulation

               -  International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless
                  subject is receiving anticoagulant therapy as long as PT or PTT is within
                  therapeutic range of intended use of anticoagulants

               -  Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is
                  receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
                  of intended use of anticoagulants

          -  Creatinine clearance should be calculated per institutional standard.

          -  Female subject of childbearing potential must have a negative urine or serum pregnancy
             within 72 hours prior to receiving the first dose of study medication. If the urine
             test is positive or cannot be confirmed as negative, a serum pregnancy test will be
             required.

          -  Female subjects of childbearing potential must be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication (Reference
             Section 7.4). Subjects of childbearing potential are those who have not been
             surgically sterilized or have not been free from menses for > 1 year.

          -  Male subjects must agree to use an adequate method of contraception starting with the
             first dose of study therapy through 120 days after the last dose of study therapy.

        Exclusion Criteria:

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment. Subjects requiring systemic steroids are excluded from the trial. The use
             of physiologic doses of corticosteroids may be approved after discussion with the
             sponsor.

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  Hypersensitivity to pembrolizumab or any of its excipients.

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier.

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
             baseline) from adverse events due to a previously administered agent.

               -  Note: Subjects with ≤ Grade 2 neuropathy and alopecia are an exception to this
                  criterion and may qualify for the study.

               -  Note: If subject received major surgery, they must wait ≥ 3 weeks prior to
                  starting study treatment. They must have recovered adequately from the toxicity
                  and/or complications from the intervention prior to starting therapy.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

          -  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 an active infection requiring systemic therapy.

          -  Patients that require supplemental oxygen are excluded.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

          -  HIV+ positive patients are eligible if their CD4+ count ≥ 300/μL and they have an
             undetectable viral load. In addition, they must be currently receiving Highly Active
             Antiretroviral Therapy (HAART) and be under the care of an Infectious Diseases
             specialist.

          -  Patients with hepatitis B and hepatitis C must be under the care of viral hepatitis
             expert consultant. Patients with hepatitis B are required to be treated with anti-HBV
             treatment (e.g., entecavir). Patients with hepatitis C need to have received prior
             and/or ongoing hepatitis C treatment.

          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

James Cleary, MD, PhD, 617-632-6073, 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02919969

Organization ID

16-301


Responsible Party

Principal Investigator

Study Sponsor

Dana-Farber Cancer Institute

Collaborators

 Merck Sharp & Dohme Corp.

Study Sponsor

James Cleary, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute


Verification Date

May 2021