Pembrolizumab in Refractory Metastatic Anal Cancer

Learn more about:
Related Clinical Trial
Re-optimization Based Online Adaptive Radiotherapy of Anal Cancer Bone-sparing Chemoradiotherapy for Anal Cancer – DACG-II Chemoradiotherapy Combined With or Without PD-1 Blockade in Anal Canal Squamous Carcinoma Patients Circulating Biomarkers in Patients With Anal Cancer Treated With Induction Chemotherapy CRTE7A2-01 TCR-T Cell for HPV-16 Positive Advanced Cervical, Anal, or Head and Neck Cancers Assessment of Patients’ Quality of Sexual Life After Anal Cancer Treatment Neoadjuvant PD-1 Blockade Combined With Chemotherapy Followed by Concurrent Immunoradiotherapy for Locally Advanced Anal Canal Squamous Carcinoma Patients Pencil Beam Proton Therapy for Recurrences in Anal Cancer Patients Previously Treated With Radiotherapy (DACG 5) Hyperthermia Enhanced Re-irradiation of Loco-regional Recurrent Tumors Detecting HPV DNA in Anal and Cervical Cancers ANCA II – Quality of Life and Functional Outcome in Patients With Anal Cancer RTX-321 Monotherapy in Patients With HPV 16+ Tumors Anal Injury Screening for High Risk HPV M7824 in Subjects With HPV Associated Malignancies Multimodal Monitoring of Radiotherapy Response in Squamous Cell Cancer Avastin/[18-F]-5-fluorouracil PET/CT Imaging Feasibility Project Assessment of Health Related Quality of Life in Patients Treated for Rectal Cancer Octreotide in Preventing or Reducing Diarrhea in Patients Receiving Chemoradiotherapy for Anal or Rectal Cancer Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies Function Following Laser for Anal Intraepithelial Neoplasia (FLAN) A Message Framing Intervention for Increasing Parental Acceptance of Human Papillomavirus Vaccination Anal Sphincter Prosthesis in Treating Patients Who Are Undergoing Surgery for Anal or Rectal Cancer Phase 2 Study of ADXS11-001 in Subjects With Carcinoma of the Anorectal Canal Pilot Study to Determine the Safety and Efficacy of Gardasil Against the Human Papilloma Virus (HPV) in HIV-infected Men Assessment of Symptom-Related Cytokines in Lung and Gastrointestinal (GI) Cancer Patients Identification of Predictive Factors for Physiological Hypermetabolism of the Anal Canal in 18F-FDG PET / CT Early Rectal Cancer: Endoscopic Submucosal Dissection or Transanal Endoscopic Microsurgery? Drainage Seton With Flap Versus EAS Preserving Seton in Treatment of Transsphincteric Anal Fistula HPV-SAVE: 9-Valent HPV Vaccine for High-Grade Anal Dysplasia Radiation Dosimetry Study Comparing 2 Different Patient Setups in Anal/Rectal Cancer Patients Comparing Two Types of Swabs in Collecting Cell Samples for Anal Pap Tests and Human Papillomavirus Tests in Men Who Have Sex With Men The HPV-SAVE Study Team: HPV Screening and Vaccine Evaluation in Men Who Have Sex With Men High-Resolution Anoscopy Perceived Discomfort Study Infrared Coagulator Ablation or Observation in Preventing Anal Cancer in HIV-Positive Patients With Anal Neoplasia Image Fusion PET, CT and 3D-ultrasound Examinations Hybrid Capture 2 Human Papiloma Virus (HPV) High-Risk Anal DNA Test ART: Anal Squamous Cell Carcinoma: Investigation of Functional Imaging During chemoRadioTherapy Anal HPV Tests in Screening for Cell Changes in the Anus in Patients With HIV Molecular Genetic and Pathological Studies of Anal Tumors Intensity-Modulated Radiation Therapy, Fluorouracil, and Mitomycin C in Treating Patients With Invasive Anal Cancer Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer QOL & Functional Outcomes After Combined Modality Tx for Anal CA: Comparison of Conventional vs IMRT A Study of mDCF in Combination or Not With Atezolizumab in Advanced Squamous Cell Anal Carcinoma Chemotherapy Plus Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer Infrared Coagulation in Preventing Anal Cancer in Patients With HIV Who Have Anal Neoplasia Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer Topical MTS-01 for Dermatitis During Radiation and Chemotherapy for Anal Cancer Radiochemotherapy +/- Durvalumab for Locally-advanced Anal Carcinoma. A Multicenter, Randomized, Phase II Trial of the German Anal Cancer Study Group Intrafractional Vaginal Dilation in Anal Cancer Patients Undergoing Pelvic Radiotherapy Screening for HIV-Associated Anal Cancer Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer Study of IMRT Radiotherapy Concurrent Chemothrerapy for Anal Cancer A Prospective, Open-Label, Multi-center Comparison of Lymphoseek Identified Lymph Nodes and Clinically Identified Lymph Nodes of Subjects With Known Cancer of the Anus Prospective Observational Trial to Evaluate Quality of Life After Definitive Chemoradiation in Patients With Anal Cancer (LANACARE) Radiation Therapy Plus Fluorouracil With or Without Additional Chemotherapy in Treating Patients With Primary Anal Cancer Prospective Cohort on Quality of Sexual Life Among Men Who Have Sex With Men Treated for Anal Cancer With Concurrent Chemotherapy and Intensity-modulated Radiotherapy Trial To Test Safety And Efficacy Of Vaccination For Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer SGN-00101 in Preventing Anal Cancer in Patients With HIV Who Have Anal Neoplasia Anal Cancer Radiotherapy Study Radiation Therapy, Mitomycin, and Either Fluorouracil or Cisplatin in Treating Patients With Locally Advanced Anal Cancer Radiation Therapy, Cisplatin, Fluorouracil, and Cetuximab in Treating Patients With Locally Advanced Anal Cancer Individual Following in Anal Cancer With PET/CT Anal Cancer Screening Study The Prevent Anal Cancer Self-Swab Study Shared Decision Making With Anal Cancer Patients on Radiation Dose Predictive Value of FMISO-PET, FDG-PET-CT, DWI-MRI and DCE-MRI Scans for Patients With Anal Cancer Receiving Radiotherapy +/- Chemotherapy Quality of Life in Patients With Anal Cancer Functional Outcomes Following Anal Cancer Treatment Pembrolizumab in Refractory Metastatic Anal Cancer A Phase I/II Evaluation of ADXS11-001, Mitomycin, 5-fluorouracil (5-FU) and IMRT for Anal Cancer

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

      The following intervention will be involved in this study:


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


Primary Outcome

Overall Response Rate

Secondary Outcome

 PD-L1 Positive Response Rate


Anal Cancer



Study Arms / Comparison Groups

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


* 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


Estimated Enrollment


Start Date

October 11, 2016

Completion Date

March 2023

Primary Completion Date

December 2021

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

               -  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

          -  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

          -  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

          -  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




18 Years - N/A

Accepts Healthy Volunteers



James Cleary, MD, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

Dana-Farber Cancer Institute


 Merck Sharp & Dohme LLC

Study Sponsor

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

Verification Date

April 2022