Checkpoint Inhibition In Pediatric Hepatocellular Carcinoma

Brief Title

Checkpoint Inhibition In Pediatric Hepatocellular Carcinoma

Official Title

The Role of Checkpoint Inhibition in Relapsed/Refractory Pediatric Hepatocellular Carcinoma: Clinical Efficacy and Biologic Correlates - A Phase II Study

Brief Summary

      This research study is studying an immunotherapy drug (pembrolizumab or KEYTRUDA) as a
      possible treatment for pediatric hepatocellular carcinoma.

Detailed Description

      Patients who fulfill eligibility criteria will be entered into the trial to receive
      pembrolizumab or KEYTRUDA

      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. In the case of this
      trial, the investigators are studying whether pembrolizumab can treat pediatric
      hepatocellular carcinoma.

      The FDA (the U.S. Food and Drug Administration) has not approved pembrolizumab for your
      specific disease but it has been approved for other uses in adults. Checkpoint inhibitors are
      in early-phase study in pediatric patients across diagnoses.

      In this research study, the investigators plan to investigate whether pediatric patients with
      hepatocellular carcinoma experience stable disease or response to pembrolizumab. In addition,
      the investigators would like to explore different biological factors of the tumor and immune
      system that might help us predict whether pediatric patients with HCC may benefit from
      treatment with pembrolizumab.

Study Phase

Phase 2

Study Type


Primary Outcome

Immune-related best overall response (irBOR)

Secondary Outcome

 Progression-free survival (PFS)


Hepatocellular Carcinoma, Childhood



Study Arms / Comparison Groups

Description:  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.


* 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

November 1, 2020

Completion Date

January 1, 2023

Primary Completion Date

January 1, 2023

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  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

          -  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

                    -  If liver function studies are more elevated than the thresholds above, and
                       if if this elevation is felt secondary to tumor, patients may still be
                       eligible for enrollment after discussion with the study PI.

               -  Adequate Renal and Metabolic Function defined as:

                    -  A serum creatinine based on age/gender as follows:

                    -  Age Maximum Serum Creatinine (mg/dL) Male Female

                    -  1 to <2 years 0.6 0.6

                    -  2 to <6 years 0.8 0.8

                    -  6 to <10 years 1.0 1.0

                    -  10 to <13 years 1.2 1.2

                    -  13 to <16 years 1.5 1.4

                    -  >16 years 1.7 1.4

               -  OR

                    -  Creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine
                       levels above institutional normal.

                    -  Amylase ≤ 1.5 x ULN

                    -  Lipase ≤ 1.5 x ULN

               -  Adequate Thyroid Function defined as:

                    -  TSH ≤1.5 ULN. Patients can be receiving thyroid supplementation.

          -  Confirmation of Insurance Pre-authorization approval for Pembrolizumab.

          -  Patients, their parent, and/or legally authorized representative must be able to
             understand and be willing to sign a written informed consent document. Assent for
             participants < 18 years will follow institutional guidelines. The protocol will
             require approval by each institution's Institutional Review Board.

          -  The effects of pembrolizumab on the developing human fetus are unknown. For this
             reason, patients of child-bearing and child-fathering potential must agree to use
             adequate contraception (hormonal or barrier method of birth control; abstinence) prior
             to study entry, for the duration of study participation, and for 4 months after
             completion of pembrolizumab administration. Should a female become pregnant or suspect
             she is pregnant while she or her partner is participating in this study, she should
             inform her treating physician immediately. Males treated or enrolled on this protocol
             must also agree to use adequate contraception prior to the study, for the duration of
             study participation, and 4 months after completion of pembrolizumab administration.

          -  Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy
             test within 24 hours of each treatment.

          -  A tumor sample must be available for submission to the central laboratory (Dana-Farber
             Cancer Institute, see Section 9). If surgery was performed at the time of recurrence,
             this sample, in addition to a diagnostic sample should be submitted. If no
             re-operation was performed, archived tissue from diagnosis or the most recent
             procedure should be submitted (see section 9 for further details regarding tissue

        Exclusion Criteria:

          -  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.

          -  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 a history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to pembrolizumab are not eligible. History of severe
             allergy to monoclonal antibody therapies (i.e. anaphylaxis) are likewise an exclusion.

          -  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

          -  Patients with prior solid organ transplantation are not eligible.




N/A - 30 Years

Accepts Healthy Volunteers



Allison O'Neill, MD, 877-DF-TRIAL, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Allison O'Neill

Study Sponsor

Allison O'Neill, MD, Principal Investigator, Dana-Farber Cancer Institute

Verification Date

February 2021