Checkpoint Inhibition In Pediatric Hepatocellular Carcinoma

NCT04134559 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 19-338
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 5

Brief Summary

This research study is studying an immunotherapy drug (pembrolizumab or KEYTRUDA) as a possible treatment for pediatric hepatocellular carcinoma or hepatocellular neoplasm not otherwise specified (HCN NOS).

Conditions

Hepatocellular Carcinoma, Childhood; Fibrolamellar Carcinoma; Liver Cancer; Liver Cancer, Pediatric

Keywords

Hepatocellular Carcinoma Childhood; Fibrolamellar Carcinoma; Liver Cancer; Liver Cancer Pediatric

Outcome Measures

Primary Outcomes (1)

• Immune-related best overall response (irBOR)

  irRECIST criteria

  63 Days

Secondary Outcomes (5)

• Progression-free survival (PFS)

  enrollment to progression (defined by irRECIST criteria) or death (whichever event occurs first), or to date of last contact up to 100 months

• Expression levels of infiltrating immune cells and markers of checkpoint inhibition on pre-treatment specimens

  2 Years

• Percent change immune cell phenotype, cytokines, and circulating tumor DNA

  2 Years

• Number of Participants with DLT

  2 Years

• DNA sequencing of specimens

  2 Years

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Pembrolizumab will be administered every 3 weeks at a dose of 2mg/kg/dose (max: 200mg) with 21 consecutive days defined as a treatment cycle.

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab will be administered every 3 weeks, at predetermined dose with 21 consecutive days defined as a treatment cycle.

Also known as: Keytruda

Pembrolizumab

Eligibility Criteria

• Age: 0 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: Patients must be \<30 years of age at the time of study enrollment.
• Diagnosis: Patients must have relapsed/refractory, histologically confirmed HCC to be eligible for enrollment. Patients with hepatocellular neoplasm not otherwise specified (HCN NOS) will also be eligible.
• Disease Status: Participants must have measurable disease by RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) measured at ≥20 mm with conventional technique or ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 10 for the evaluation of measurable disease.
• Performance Level: Karnofsky performance status ≥ 60% for patients ≥ 16 years of age or Lansky ≥ 60% for patients \< 16 years of age.
• Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy.
• Patients must not have received standard or targeted treatment regimens within 14 days of initiation of treatment with pembrolizumab.
• Patients must not have received prior radiotherapy within 7 days of initiation of treatment with pembrolizumab. Patients who have experienced radiation-induced adverse events must recover to a grade 1 prior to enrollment.
• Organ Function Requirements: Participants must have normal organ and marrow function as defined below:
• Adequate Bone Marrow Function defined as:
• Peripheral absolute neutrophil count (ANC) ≥ 750/μL
• Platelet count ≥ 75,000/μL (can be transfused)
• Adequate Liver Function defined as:
• Total bilirubin \< 1.5 x institutional upper limit of normal (ULN)
• AST(SGOT) ≤ 2.5 x ULN
• ALT(SGPT) ≤ 2.5 x ULN

You may not qualify if:

• Participants who are receiving any other investigational agents are not eligible.
• Participants who have received checkpoint inhibitors (PD-1, PD-L1, and CTLA-4 inhibitors) are not eligible.
• Participants who have received antibody-based therapies are not eligible if they are within 3 half-lives of receipt of the last antibody dose.
• Participants who are receiving chronic steroids are not eligible.Chronic steroids are defined as either \> or = 2mg/kg/day of body weight or \> or = 20mg/day of prednisone or equivalent for persons who weigh \> or = 10kg administered for \> or = 14 consecutive days.
• Participants who are receiving anti-inflammatory or immunosuppressive medications are not eligible.
• Participants with known autoimmune disease, with the exceptions of childhood asthma or atopic dermatitis, are not eligible.
• Patients with a history of a positive test for human immunodeficiency virus or acquired immunodeficiency syndrome are not eligible.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible.
• Patients with prior solid organ transplantation are not eligible.

Sponsors & Collaborators

• Allison O'Neill, MD: lead

Study Sites (5)

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Related Publications (2)

• Short SS, Kastenberg ZJ, Wei G, Bondoc A, Dasgupta R, Tiao GM, Watters E, Heaton TE, Lotakis D, La Quaglia MP, Murphy AJ, Davidoff AM, Mansfield SA, Langham MR, Lautz TB, Superina RA, Ott KC, Malek MM, Morgan KM, Kim ES, Zamora A, Lascano D, Roach J, Murphy JT, Rothstein DH, Vasudevan SA, Whitlock R, Lal DR, Hallis B, Butter A, Baertschiger RM, Lapidus-Krol E, Putra J, Tracy ER, Aldrink JH, Apfeld J, Le HD, Park KY, Rich BS, Glick RD, Fialkowski EA, Utria AF, Meyers RL, Riehle KJ. Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study. Cancer. 2022 Jul 15;128(14):2786-2795. doi: 10.1002/cncr.34256. Epub 2022 May 13.

  PMID: 35561331 DERIVED

• O'Neill AF, Church AJ, Perez-Atayde AR, Shaikh R, Marcus KJ, Vakili K. Fibrolamellar carcinoma: An entity all its own. Curr Probl Cancer. 2021 Aug;45(4):100770. doi: 10.1016/j.currproblcancer.2021.100770. Epub 2021 Jul 1.

  PMID: 34272087 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Fibrolamellar hepatocellular carcinoma; Liver Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Allison O'Neill, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

DFCI Clinical Trials Hotline

CONTACT

877-DF-TRIAL; allison_oneill@dfci.harvard.edu

Study Design

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

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 22, 2019
• Study Start: November 1, 2020
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (5)