Hepatocellular Carcinoma, ChildhoodPhase 2NCT04134559
Checkpoint Inhibition In Pediatric Hepatocellular Carcinoma
A Phase 2 study testing Pembrolizumab in people with Hepatocellular Carcinoma, Childhood and Fibrolamellar Carcinoma, run by Allison O'Neill, MD at 5 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 0 to 30 years
- Conditions the study is for
- Hepatocellular Carcinoma, Childhood, Fibrolamellar Carcinoma, Liver Cancer
- What is being tested?
- Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 5 sitesUnited States
- Study dates
- 1 Nov 2020to 1 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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
- If liver function studies are more elevated than the thresholds above, and if this elevation is felt secondary to tumor, patients may still be eligible for enrollment after discussion with the study PI.
- -- 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 specifications).
Who cannot join
- 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.
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- 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 eligible.
- Patients with prior solid organ transplantation are not eligible.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
Children's Hospital Boston
Boston, Massachusetts, 02115
Allison O'Neill, MD
Allison O'Neill, MD
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Allison O'Neill, MD, 617-632-4202
Allison O'Neill, MD
- Recruiting
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45229
James Geller, MD, 513-636-6312, james.geller@cchmc.org
- Recruiting
Baylor College of Medicine
Houston, Texas, 77030
Jennifer Foster, MD, MPH, 832-824-4646, jhfoster@bcm.edu
- Recruiting
University of California San Francisco
San Francisco, California, 94143
Arun Rangaswami, MD, 415-476-3831, arun.rangaswami@ucsf.edu
About this study
Official title: The Role of Checkpoint Inhibition in Relapsed/Refractory Pediatric Hepatocellular Carcinoma: Clinical Efficacy and Biologic Correlates - A Phase II Study
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).
Read the 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.
- Conditions
- Hepatocellular Carcinoma, Childhood, Fibrolamellar Carcinoma, Liver Cancer, Liver Cancer, Pediatric
- Being tested
- Pembrolizumab
- Keywords
- Hepatocellular Carcinoma Childhood, Fibrolamellar Carcinoma, Liver Cancer, Liver Cancer Pediatric
- Medical subject headings
- Carcinoma, Hepatocellular, Fibrolamellar hepatocellular carcinoma, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab will be administered every 3 weeks, at predetermined dose with 21 consecutive days defined as a treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune-related best overall response (irBOR)
irRECIST criteria
Measured: 63 Days
Secondary outcomes (5)
Progression-free survival (PFS)
irRECIST criteria
Measured: 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
Expression levels of infiltrating immune cells and markers of checkpoint inhibition, as assessed by immunohistochemistry on pre-treatment specimens, quantified using a semi-quantitative scoring system based on percent of cells showing positive staining.
Measured: 2 Years
Percent change immune cell phenotype, cytokines, and circulating tumor DNA
summarized using descriptive statistics.
Measured: 2 Years
Number of Participants with DLT
organ affected or laboratory determination, severity (by NCI CTCAE v5.0), and attribution.
Measured: 2 Years
DNA sequencing of specimens
Descriptive analysis of gene mutation patterns correlating with disease response to checkpoint inhibition
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2019
- Study start1 Nov 2020
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular Carcinoma, ChildhoodStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Allison O'Neill, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Allison O'Neill, MD, Dana-Farber Cancer Institute
- Investigators
- Allison O'Neill, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04134559
- Sponsor's protocol ID
- 19-338
- Status last verified
- Feb 2026
- First submitted
- 2 Oct 2019
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Publications
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.
PubMed 35561331O'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.
PubMed 34272087
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Checkpoint Inhibition in Relapsed/Refractory Pediatric Hepatocellular Carcinoma: Clinical Efficacy and Biologic Correlates - A Phase II Study
- ClinicalTrials.gov ID
- NCT04134559
- Acronym / sponsor ID
- 19-338
- Conditions
- Hepatocellular Carcinoma, Childhood, Fibrolamellar Carcinoma, Liver Cancer, Liver Cancer, Pediatric
- Keywords
- Hepatocellular Carcinoma Childhood, Fibrolamellar Carcinoma, Liver Cancer, Liver Cancer Pediatric
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Allison O'Neill, MDUniversity, hospital or other
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 22 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: PembrolizumabPembrolizumab will be administered every 3 weeks at a dose of 2mg/kg/dose (max: 200mg) with 21 consecutive days defined as a treatment cycle. |
Who may qualify
- Ages
- 0 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (37 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaPembrolizumab will be administered every 3 weeks, at predetermined dose with 21 consecutive days defined as a treatment cycle. | Drug | Pembrolizumab |
Primary outcome
Immune-related best overall response (irBOR)
Time frame: 63 Days
irRECIST criteria
5 secondary outcomes
Progression-free survival (PFS)
Time frame: 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
Time frame: 2 Years
Percent change immune cell phenotype, cytokines, and circulating tumor DNA
Time frame: 2 Years
Number of Participants with DLT
Time frame: 2 Years
DNA sequencing of specimens
Time frame: 2 Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2026.
- Derived from this study: PubMed 35561331Short 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.
- Derived from this study: PubMed 34272087O'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.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Allison O'Neill, MD principal investigator
Dana-Farber Cancer Institute
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Hepatocellular Carcinoma, Childhood and Fibrolamellar Carcinoma, run by Allison O'Neill, MD at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 37 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact DFCI Clinical Trials Hotline (877-DF-TRIAL, allison_oneill@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immune-related best overall response (irBOR) (time frame: 63 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04134559, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2026.