Clinical trial NCT04313868: GEN2 Directed Cancer Immunotherapy Trial
Official title: A Phase 1 Dose Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of GEN2 in Refractory Patients With Primary Hepatocellular Carcinoma or Tumors Metastatic to the Liver
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Metastatic Cancer
Keywords: Liver Metastasis
Liver Cancer
Lead sponsor: GenVivo, Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-18
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Dose Escalation Trial
Primary purpose: OTHER

Brief summary: Phase 1, non-randomized, open label dose escalation clinical trial evaluating the safety of GEN2 in participants with primary \& metastatic liver tumors.

Detailed description: This clinical trial will be divided into two phases: Phase IA in which the dose, route, and schedule of the GEN2 administration is determined and Phase IB which is designed to explore the activity of GEN2 in patients of a defined or several defined tumor types and stages based on the Phase IA data of GEN2.

Phase IA is divided into three routes of administration: (a) Phase 1A.1 which explores peripheral IV infusion; (b) Phase IA.2 which investigates hepatic arterial infusion and (c) Phase IA.3 which examines intratumoral delivery.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of histologically documented, advanced stage, primary or metastatic adult solid tumor(2) in the liver that are refractory to standard therapy or for which no curative standard therapy exists.
* Evidence of radiographically measurable or evaluation disease on a baseline PET-CT scan.
* All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedures must have resolved to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) (Version 4.03) Grade \< 1.
* Patient must be legally considered an adult in the country in which they are participating in the study.
* Last dose of antineoplastic therapy, except for hormonal therapy, must be \> 21 days. External beam radiotherapy must have been \<25% bone marrow-containing skeleton.
* Patients may be Hepatitis B and C positive.
* Patients may have intracranial metastases of any number if they have been brain irradiated and stable for 6 weeks. Patients may be taking anti-seizure medicines but must not be on steroids. Last dose of steroids must be \>7 days.
* Karnofsky performance status must be \> or = 70
* Childs-Pugh Classification Score of 7 or less
* Life Expectancy of at least 3 months
* Patients must be able to travel to alternate medical center for PET/CT scans, if necessary.
* Meet the required baseline laboratory data
* Signed informed consent indicating that they are aware of the neoplastic nature of their disease and have been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks and discomforts.
* Willing and able to comply with scheduled visits, treatment plan, and laboratory tests.

Exclusion Criteria:

* Concurrent therapy with anticancer agent including any other investigational agent.
* Existing intracranial edema or CVA within 6 months of screening
* Pregnant or breast-feeding women. Female patients must agree to use effective contraception, must be surgically sterile or must be post-menopausal. Male patients must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the Investigator or a designated associate. All at-risk female patients must have a negative pregnancy test within 7 days prior to start of the study treatment.
* Clinically significant cardiac disease (New York Heart Associate, Class III or IV)
* Dementia or altered mental status that would prohibit informed consent.
* Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study.
* Known side effects to antivirals in the ganciclovir class
* Patients who are known to be HIV positive.
* Patients must not be taking steroids at the time of screening. Last dose of steroids must be \>7 days.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: First 3 weeks of GEN2 Administration
measure: Dose Limiting Toxicity (DLT)
timeFrame: First 3 weeks of GEN2 Administration
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: First 3 weeks of GEN2 Administration
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Treatment Initiation until 30 days after last dose of GEN2
Secondary outcomes:
measure: Plasma pharmacokinetics of GEN2
timeFrame: During Week 1 of Cycle 1, Cycle 2 & Cycle 6 (each cycle is 28 days)
measure: HSV-TK-m2 protein expression from GEN2 via serial [18F]FHBG PET and/or SPECT imaging
timeFrame: Day 3-8 of GEN2 Treatment
measure: Preliminary Evidence of anti-tumor activity of GEN2
timeFrame: Week 9 and every 6 weeks thereafter through study completion, an average of 8 months.
measure: Clinical research testing for antibodies to retrovector gp70 env, replication-competent retrovirus in peripheral blood lymphocytes (PBLs); vector integration into genomic DNA of PBLs, and circulating hGM-CSF protein
timeFrame: Cycle 1, Cycle 2, Cycle 6, after 6th month on treatment, annually thereafter
Other outcomes:
Locations:
city: Makati City
country: Philippines
facility: Makati Medical Center
city: Pasig City
country: Philippines
facility: The Medical City
city: Quezon City
country: Philippines
facility: National Kidney and Transplant Institute
city: Quezon City
country: Philippines
facility: St. Luke's Medical Center
Study officials:
affiliation: St. Luke's Medical Center - Quezon City
name: Priscilla B Caguioa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Makati Medical Center
name: Maria Belen E Tamayo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Medical City
name: John P Querol, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Kidney and Transplant Institute
name: Necy S Juat, MD
role: PRINCIPAL_INVESTIGATOR
References: