Pembrolizumab in Patients With Locally Advanced or Metastatic Skin Cancer

• ClinicalTrials.gov Identifier: NCT02964559
• Recruitment Status: Active, not recruiting
• First Posted: November 16, 2016
• Last Update Posted: March 8, 2022
• Sponsor: Emory University
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Ragini Kudchadkar, MD, Emory University

Study Description

Brief Summary:

This phase II trial studies how well pembrolizumab works in treating patients with skin cancer that has spread from where it started to nearby tissue, lymph nodes, or other parts of the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Condition or disease	Intervention/treatment	Phase
Recurrent Skin Carcinoma; Skin Squamous Cell Carcinoma	Biological: Pembrolizumab	Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

-To establish the response rate of pembrolizumab in metastatic cutaneous squamous cell carcinoma.

SECONDARY OBJECTIVES:

-To determine the 6-month progression-free survival and 1 year overall survival of metastatic cutaneous squamous cell carcinoma of the skin (cSCC) treated with pembrolizumab.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 8-12 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Pembrolizumab (MK-3475) in Metastatic Cutaneous Squamous Cell Carcinoma
• Actual Study Start Date: January 27, 2017
• Estimated Primary Completion Date: February 27, 2023
• Estimated Study Completion Date: February 27, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment (pembrolizumab); Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.	Biological: Pembrolizumab; Given IV; Other Names: Keytruda; Lambrolizumab; MK-3475; SCH 900475

Outcome Measures

Primary Outcome Measures :

1. Response rate of pembrolizumab [ Time Frame: Up to 1 year after treatment discontinuation ]
   Will be estimated as percentage and 95% confidence interval will be constructed assuming a binomial distribution.

Secondary Outcome Measures :

1. Overall survival [ Time Frame: Up to 1 year after treatment discontinuation ]
   Will be estimated with Kaplan Meier method and compared between different groups using Logrank test. Cox proportional model will be further employed to assess the treatment effect on survival with and without adjusting for other factors.
2. Progression-free survival [ Time Frame: Up to 6 months after treatment discontinuation ]
   Will be estimated with Kaplan Meier method and compared between different groups using Logrank test. Cox proportional model will be further employed to assess the treatment effect on survival with and without adjusting for other factors.

Other Outcome Measures:

1. Programmed death-ligand 1 (PD-L1) expression in tumor specimens [ Time Frame: Up to 1 year after treatment discontinuation ]
   Will determine PD-L1 staining on tumor specimens by flow cytometry.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• All subjects must have cutaneous squamous cell carcinoma that is not curable by surgery or radiation; both locally advanced and metastatic squamous cell carcinoma will be included.
• Be willing and able to provide written informed consent/assent for the trial.
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (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.
• Be willing to undergo normal skin biopsy prior to initiation of treatment and after treatment.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
• Absolute neutrophil count (ANC) ≥ 1,500/microliter (mcL)
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) ≥ 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
• Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Albumin ≥ 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants.
• Activated partial thromboplastin rime (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.
• Female subject of childbearing potential should 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 should 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; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
• Male subjects should 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:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• 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, patients with human immunodeficiency virus (HIV) adequately controlled on antiretrovirals (undetectable viral load) and patients with chronic lymphocytic leukemia (CLL) not requiring systemic treatment will be included; in addition, steroids for physiologic replacement will be allowed (must be equal to or less than 10mg of prednisone/day).
• 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 are an exception to this criterion and may qualify for the study.
  • Note: if subject received major surgery, 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 that has undergone potentially curative therapy or in situ cervical cancer. Asymptomatic CLL, not requiring intervention will be included as long as patients meet routine laboratory parameters of the study as outlined above. In addition, patients who have undergone curative bone marrow transplant and currently not requiring immunosuppression, will be allowed on study.
• 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 a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy; exception HIV on antiretrovirals with negative viral load.
• 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-programmed cell death (PD)-1, anti- programmed cell death 1 ligand (PD-L)1, or anti-PD-L2 agent.
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected).
• Has received a live vaccine within 30 days of planned start of study therapy. 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.
• cSCC that is curable via radiation or surgery; palliative radiation is allowed as long as measurable disease outside radiation field is present for study.

Contacts and Locations

Locations

United States, Georgia

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Ragini Kudchadkar; Emory University

More Information

• Responsible Party: Ragini Kudchadkar, MD, Principal Investigator, Emory University
• ClinicalTrials.gov Identifier: NCT02964559
• Other Study ID Numbers: IRB00087412; NCI-2016-00831 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); Winship3185-16 ( Other Identifier: Emory University/Winship Cancer Institute )
• First Posted: November 16, 2016
• Last Update Posted: March 8, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents