Neoadjuvant PD-1 Blockade in Patients with Stage IIB/C Melanoma

NCT03757689 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: UPCC 09618832023CRU
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 3

Brief Summary

The main purpose of this study is to determine the rate of positive sentinel lymph nodes (i.e. the closest draining lymph node(s) to the primary melanoma site) and to test whether treatment with pembrolizumab before surgery to remove melanoma reduces the rate of positive sentinel lymph nodes in patients with Stage IIB/C melanoma. Subjects with stage II melanoma will receive one dose of pembrolizumab 200 mg, then undergo standard definitive surgery with wide excision and sentinel lymph node (SLN) biopsy approximately 3 weeks after the initial dose of pembrolizumab. Post-operatively, subjects will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks.

Conditions

Melanoma

Keywords

Stage IIB/C

Outcome Measures

Primary Outcomes (2)

• SLN Positivity Rate

  To determine the SLN positivity rate and test whether the SLN positivity rate is reduced in high risk stage II patients undergoing neoadjuvant PD-1 blockade.

  3 Weeks

• Safety and Tolerability as measured by observed adverse events.

  All observed adverse events which occur anytime from the initiation of study therapy to 30 days after the final dose of pembrolizumab will be graded and tabled.

  Approximately 5 Years

Secondary Outcomes (2)

• Disease-Free Survival (DFS)

  Approximately 5 Years

• Overall Survival

  Approximately 5 Years

Study Arms (1)

Neoadjuvant Pembrolizumab

EXPERIMENTAL

Subjects will receive one dose of pembrolizumab 200 mg. Approximately 3 weeks after the initial dose of pembrolizumab, subjects will undergo wide excision and sentinel lymph node (SLN) biopsy. Post-operatively, subjects will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks.

Drug: Pembrolizumab; Procedure: Wide Excision and Sentinel Lymph Node (SLN) Biopsy

Interventions

Pembrolizumab DRUG

Pre-Surgery: Pembrolizumab, one 200mg dose; Post-Surgery: Pembrolizumab, 200 mg every 3 weeks.

Neoadjuvant Pembrolizumab

Wide Excision and Sentinel Lymph Node (SLN) Biopsy PROCEDURE

Wide excision and SLN biopsy and pathologic assessment of tissue will be performed per standard of care.

Neoadjuvant Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject must have clinical stage IIB or IIC resectable MEL. Subjects may not have a diagnosis of uveal or mucosal melanoma.
• Either the subject or the subject's legal representative must be willing and able to provide written informed consent for the trial.
• The subject must be ≥18 years of age on day of signing informed consent.
• The subject must have a performance status of 0 or 1 on the ECOG Performance Scale.
• The subject must demonstrate adequate organ function as defined in Table 1; all screening labs must be performed within 21 days of treatment initiation.
• System Laboratory Value
• Hematologic
• ANC ≥1500/mcL
• Platelets ≥100,000/mcL
• Hemoglobin ≥9 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
• ≥50 mL/min for subject with creatinine levels \>1.5 X institutional ULN
• Hepatic
• Serum total bilirubin ≤1.5 X ULN OR

You may not qualify if:

• Subject has unresectable disease; i.e. in the opinion of the surgical oncologist, all of the subject's melanoma cannot be completely removed with a clear margin.
• A woman of child bearing potential who has a positive urine pregnancy test within 72 hours prior to first dose of study drug (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), interferon, high dose IL-2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy are an exception to this criterion.
• If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Subject has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to study Day 1.
• Has 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 (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or requires active treatment. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 3 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has evidence of active interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (3)

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; sarcolipin; Biopsy

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Giorgos Karakousis, MD

  Abramson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2018
• First Posted: November 29, 2018
• Study Start: May 6, 2019
• Primary Completion: December 1, 2024
• Study Completion (Estimated): February 1, 2027
• Last Updated: February 11, 2025

Record last verified: 2025-02

Locations

US (3)