A Pilot Study of a DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma

Who is this study for? Patients with Fibrolamellar Hepatocellular Carcinoma
Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

The primary objective of the trial is the safety and tolerability of administering a vaccine targeting the DNAJB1-PRKACA fusion kinase, in combination with nivolumab and ipilimumab in patients with unresectable or metastatic FLC and with non-FLC solid tumors and to assess the T-cell response.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 12
Healthy Volunteers: f
View:

• Cohort A and B: Must have histologically confirmed FLC (fibrolamellar hepatocellular cancer) that is metastatic or unresectable.

• Cohort C: Patients with histologically proven metastatic or unresectable DNAJB1-PRKACA fusion transcript positive solid tumor malignancies, non-FLC solid tumors.

• Cohort A and B: Age \> 12 years. Note: Subjects age \> 12 years but \<18 are eligible to enroll only after 6 adult patients have enrolled on the study.

• Cohort A and B: Patients \< 18 years old must have a body weight ≥40 kg.

• Cohort C: Patients must be Age ≥ 18 years.

⁃ All Cohorts:

• Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-sequencing, DNA-sequencing, or in situ hybridization in the archival tissue.

• ECOG performance status of ≤2 (Karnofsky ≥60%)

• Patients must have adequate liver, kidney and marrow function defined by study-specified laboratory tests prior to initial study drug.

• Patients must have measurable disease per RECIST 1.1.

• Must be willing to provide tissue and blood samples for mandatory translational research.

• Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.

• Men must use acceptable form of birth control while on study.

• Ability to understand and willingness to sign a written informed consent document.

• Patients previously treated with the vaccine targeting the DNAJB1-PRKACA fusion kinase in combination with nivolumab and ipilimumab, who, in the opinion of the principal investigator, had clinical or radiological benefits.

• Patients \< 18 years old must have a body weight ≥40 kg.

• ECOG performance status of ≤2 (Karnofsky ≥60%, see Appendix A).

• Patients must have adequate liver, kidney and marrow function defined by study-specified laboratory tests prior to initial study drug.

• Patients must have measurable disease per RECIST 1.1.

• Willingness to provide tissue and blood samples for mandatory translational research.

• Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.

• Men must use acceptable form of birth control while on study.

• Ability to understand and willingness to sign a written informed consent document.

Locations
United States
Maryland
Sidney Kimmel Comprehensive Cancer Center
RECRUITING
Baltimore
Contact Information
Primary
Colleen Apostol, RN
GIClinicalTrials@jhmi.edu
410-614-3644
Backup
Marina Baretti, MD
mbarett1@jhu.edu
410-614-1058
Time Frame
Start Date: 2020-04-20
Estimated Completion Date: 2034-03-01
Participants
Target number of participants: 56
Treatments
Experimental: DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab
Cohort A: Patients with FLC cancer with no prior checkpoint inhibitor treatment. Cohort B: Patients with FLC cancer with prior checkpoint inhibitor treatment. Cohort C: Patients with non-FLC cancer (solid tumors) with prior checkpoint inhibitor treatment eligible.
Experimental: R- Enrollment: DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab
Re-enrolling patients: Patients previously treated with the vaccine targeting the DNAJB1-PRKACA fusion kinase in combination with nivolumab and ipilimumab, who, in the opinion of the principal investigator, had clinical or radiological benefits. Re-enrolling patients who come off treatment ≤ 12 months from last dose may resume therapy at the study timepoint that they stopped study therapy. Patients who came off study therapy \> 12 months of last dose (i.e. to pursue alternative therapies (for example, surgical debulking), or after completion of the 2 years of study therapy), may restart study therapy at C1D1. In both cases, if the investigator assesses a drug-related toxicity to be related to anti-CTLA4 (ie. not anti-PD(L)1) therapy, patients can be enrolled in the study with nivolumab plus FLC peptide vaccine only.
Related Therapeutic Areas
Sponsors
Collaborators: Fibrolamellar Cancer Foundation
Leads: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

This content was sourced from clinicaltrials.gov

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