Pembrolizumab in Metastatic Anal Cancer

• ClinicalTrials.gov Identifier: NCT02919969
• Recruitment Status: Recruiting
• First Posted: September 30, 2016
• Last Update Posted: May 14, 2021
• Sponsor: Dana-Farber Cancer Institute
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): James Cleary, MD, PhD, Dana-Farber Cancer Institute

Tracking Information

• First Submitted Date: September 2, 2016
• First Posted Date: September 30, 2016
• Last Update Posted Date: May 14, 2021
• Actual Study Start Date: October 11, 2016
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 26, 2020)

Overall Response Rate [ Time Frame: 36 months ]

Overall response rate of pembrolizumab in metastatic anal cancer patients will be evaluated by RECIST 1.1.

Original Primary Outcome Measures (submitted: September 28, 2016)

Overall Response Rate [ Time Frame: 36 months ]

Overall response rate of pembrolizumab in refractory, metastatic anal cancer patients will be evaluated by RECIST 1.1.

Current Secondary Outcome Measures (submitted: September 28, 2016)

• PD-L1 Positive Response Rate [ Time Frame: 36 months ]
  Response rate in PD-L1 positive metastatic anal cancer patients will be evaluated by RECIST 1.1.
• Overall Survival [ Time Frame: 36 months ]
  Evaluate the durability of pembrolizumab responses in PD-L1 positive metastatic anal cancer patients by measuring median overall survival.
• Progression Free Survival [ Time Frame: 36 months ]
  Evaluate the durability of pembrolizumab responses in PD-L1 positive metastatic anal cancer patients by measuring median progression free survival.
• Incidence of Adverse Events to Evaluate the Safety and Tolerability of Pembrolizumab [ Time Frame: Every 3 Weeks, from the time the informed consent is signed through 90 days following cessation of treatment ]
  Assess how well pembrolizumab is tolerated in patients with metastatic anal cancer by evaluating adverse events by CTCAE v4.0.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Anal Cancer

Intervention

Drug: Pembrolizumab

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.

Other Names:

• Keytruda
• MK-3475

Study Arms

Experimental: Pembrolizumab

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

Intervention: Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 28, 2016): 32
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2023
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: James Cleary, MD, PhD; 617-632-6073

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02919969
• Other Study ID Numbers: 16-301
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: James Cleary, MD, PhD, Dana-Farber Cancer Institute
• Study Sponsor: Dana-Farber Cancer Institute
• Collaborators: Merck Sharp & Dohme Corp.

Investigators

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

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: May 2021