Checkpoint Inhibition In Pediatric Hepatocellular Carcinoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04134559|
Recruitment Status : Recruiting
First Posted : October 22, 2019
Last Update Posted : September 10, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Hepatocellular Carcinoma, Childhood Fibrolamellar Carcinoma Liver Cancer Liver Cancer, Pediatric||Drug: Pembrolizumab||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Role of Checkpoint Inhibition in Relapsed/Refractory Pediatric Hepatocellular Carcinoma: Clinical Efficacy and Biologic Correlates - A Phase II Study|
|Actual Study Start Date :||November 1, 2020|
|Estimated Primary Completion Date :||January 1, 2025|
|Estimated Study Completion Date :||January 1, 2025|
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.
Pembrolizumab will be administered every 3 weeks, at predetermined dose with 21 consecutive days defined as a treatment cycle.
Other Name: Keytruda
- Immune-related best overall response (irBOR) [ Time Frame: 63 Days ]irRECIST criteria
- 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 ]irRECIST criteria
- Expression levels of infiltrating immune cells and markers of checkpoint inhibition on pre-treatment specimens [ Time Frame: 2 Years ]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.
- Percent change immune cell phenotype, cytokines, and circulating tumor DNA [ Time Frame: 2 Years ]summarized using descriptive statistics.
- Number of Participants with DLT [ Time Frame: 2 Years ]organ affected or laboratory determination, severity (by NCI CTCAE v5.0), and attribution.
- DNA sequencing of specimens [ Time Frame: 2 Years ]Descriptive analysis of gene mutation patterns correlating with disease response to checkpoint inhibition
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||0 Years to 30 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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
- 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).
- 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 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04134559
|Contact: DFCI Clinical Trials Hotline||877-DF-TRIALemail@example.com|
|United States, California|
|University of California San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Arun Rangaswami, MD 415-476-3831 firstname.lastname@example.org|
|United States, Massachusetts|
|Children's Hospital Boston||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Allison O'Neill, MD|
|Principal Investigator: Allison O'Neill, MD|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Allison O'Neill, MD 617-632-4202|
|Principal Investigator: Allison O'Neill, MD|
|United States, Ohio|
|Cincinnati Children's Medical Center||Recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: James Geller, MD 513-636-6312 email@example.com|
|United States, Texas|
|Baylor College of Medicine||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Jennifer Foster, MD, MPH 832-824-4646 firstname.lastname@example.org|
|Principal Investigator:||Allison O'Neill, MD||Dana-Farber Cancer Institute|
|Responsible Party:||Allison O'Neill, Sponsor Investigator, Dana-Farber Cancer Institute|
|Other Study ID Numbers:||
|First Posted:||October 22, 2019 Key Record Dates|
|Last Update Posted:||September 10, 2022|
|Last Verified:||September 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||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.|
Statistical Analysis Plan (SAP)
Informed Consent Form (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 email@example.com|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Hepatocellular Carcinoma Childhood
Liver Cancer Pediatric
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Antineoplastic Agents, Immunological