Hepatocellular CarcinomaPhase 1GEN2NCT04313868
GEN2 Directed Cancer Immunotherapy Trial
A Phase 1 study testing GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes) in people with Hepatocellular Carcinoma and Metastatic Cancer, run by GenVivo, Inc. at 4 sites in Philippines.
Trial summary
Phase 1, non-randomized, open label dose escalation clinical trial evaluating the safety of GEN2 in participants with primary \& metastatic liver tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Metastatic Cancer
- What is being tested?
- GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 4 sitesPhilippines
- Study dates
- 13 Jun 2014to 12 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
Philippines4 sites
Makati Medical Center
Makati City, 1229
The Medical City
Pasig
National Kidney and Transplant Institute
Quezon City, 1101
St. Luke's Medical Center
Quezon City, 1112
About this study
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
Phase 1, non-randomized, open label dose escalation clinical trial evaluating the safety of GEN2 in participants with primary \& metastatic liver tumors.
Read the 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.
- Conditions
- Hepatocellular Carcinoma, Metastatic Cancer
- Being tested
- GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes)
- Keywords
- Liver Metastasis, Liver Cancer
- Medical subject headings
- Carcinoma, Hepatocellular, Neoplasm Metastasis, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes)Drug
GEN2 is an investigational drug combining cytotoxic and immunotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1A.1: Peripheral IV | Experimental | GEN2 is administered in repeating three week cycles. On week one, GEN2 is given intravenously on three consecutive days and the presence of the HSV-TK-m2 expression is monitored by [18F]FHBG PET scanning after 3 to 8 days. Valganciclovir dosing is initiated on day 7 to 9 for 5 days. An approximately one week drug holiday follows. Receives: Drug: GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes) |
| Phase IA.2: Hepatic Artery Infusion | Experimental | GEN2 is administered in repeating three week cycles. On week one, GEN2 is given as a single hepatic artery infusion (HAI) on two successive days and the presence of the HSV-TK-m2 expression is monitored by [18F]FHBG PET scanning after 3 to 8 days. Valganciclovir dosing is initiated on day 7 to 9 for 5 days. An approximately one week drug holiday follows. Receives: Drug: GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes) |
| Phase IA.3: Intratumoral Injection | Experimental | GEN2 is administered in repeating three week cycles. On week one, GEN2 is given via injection directly into the tumor lesions on one day and the presence of the HSV-TK-m2 expression is monitored by [18F]FHBG PET scanning after 3 to 8 days. Valganciclovir dosing is initiated on day 7 to 9 for 5 days. An approximately one week drug holiday follows. Receives: Drug: GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
The MTD is the defined as the highest dose level at which, at most, one patient experiences a DLT.
Measured: First 3 weeks of GEN2 Administration
Dose Limiting Toxicity (DLT)
- Grade 4 neutropenia
- Grade 4 thrombocytopenia;
- Grade 3 or greater nausea and/or vomiting despite the use of adequate/maximal medical intervention and/or prophylaxis;
- Any Grade 3 or greater non-hematological toxicity (except Grade 3 injection site reaction, alopecia, fatigue);
- Retreatment delay of more than 3 weeks due to delayed recovery from a toxicity related to treatment with GEN2;
- Grade 3 or greater allergic (hypersensitivity) reaction despite the appropriate use of premedications (defined within the CTC as "Prolonged" (e.g., not rapidly reponsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae (e.g., renal impairment, pulmonary infiltrates).
Measured: First 3 weeks of GEN2 Administration
Recommended Phase 2 Dose (RP2D)
The RP2D will be administered for Phase 1B. It is determined when the accelerated phase ends for Phase IA and the dose assignment for a new patient in the standard dose escalation will follow a modified Fibonacci scheme. If a modified Fibonacci has already been used, the RP2D will be explored from the remaining intervals between the dose which had no DLTs and the Maximum Administered Dose (MAD).
Measured: First 3 weeks of GEN2 Administration
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Each Adverse Event is to be classified by the Investigator as serious or non-serious. The classification of the gravity of the event determines the reporting procedures to be followed.
Measured: Treatment Initiation until 30 days after last dose of GEN2
Secondary outcomes (4)
Plasma pharmacokinetics of GEN2
GEN2 PK Cmax is dose proportional.
Measured: During Week 1 of Cycle 1, Cycle 2 & Cycle 6 (each cycle is 28 days)
HSV-TK-m2 protein expression from GEN2 via serial [18F]FHBG PET and/or SPECT imaging
Identify number of participants with positive [18F] FHBG scan
Measured: Day 3-8 of GEN2 Treatment
Preliminary Evidence of anti-tumor activity of GEN2
Measure of anti-tumor efficacy based on objective tumor assessments made according to the irRECIST 1.1
Measured: Week 9 and every 6 weeks thereafter through study completion, an average of 8 months.
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
No replication-competent retrovirus. No vector integration into genomic DNA of PBLS. No GM-CSF detectable in patients after GEN2 administration
Measured: Cycle 1, Cycle 2, Cycle 6, after 6th month on treatment, annually thereafter
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2020
- Study start13 Jun 2014
- Primary completion12 Dec 2023
- Study completion12 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies 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 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Dose Escalation Trial
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- GenVivo, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Priscilla B Caguioa, MD, Principal investigator, St. Luke's Medical Center - Quezon CityMaria Belen E Tamayo, MD, Principal investigator, Makati Medical CenterJohn P Querol, MD, Principal investigator, The Medical CityNecy S Juat, MD, Principal investigator, National Kidney and Transplant Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04313868
- Sponsor's protocol ID
- EPB-002
- Acronym
- GEN2
- Status last verified
- Nov 2024
- First submitted
- 15 Jan 2020
- Last updated
- 6 Nov 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04313868
- Acronym / sponsor ID
- GEN2 / EPB-002
- Conditions
- Hepatocellular Carcinoma, Metastatic Cancer
- Keywords
- Liver Metastasis, Liver Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- GenVivo, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Jun 2014 (actual)
- Primary completion
- 12 Dec 2023 (actual)
- Study completion
- 12 Dec 2023 (actual)
- First posted
- 18 Mar 2020 (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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Dose Escalation Trial
| Arm | Type | Receives |
|---|---|---|
| Phase 1A.1: Peripheral IV | Experimental | Drug: GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes)GEN2 is administered in repeating three week cycles. On week one, GEN2 is given intravenously on three consecutive days and the presence of the HSV-TK-m2 expression is monitored by [18F]FHBG PET scanning after 3 to 8 days. Valganciclovir dosing is initiated on day 7 to 9 for 5 days. An approximately one week drug holiday follows. |
| Phase IA.2: Hepatic Artery Infusion | Experimental | Drug: GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes)GEN2 is administered in repeating three week cycles. On week one, GEN2 is given as a single hepatic artery infusion (HAI) on two successive days and the presence of the HSV-TK-m2 expression is monitored by [18F]FHBG PET scanning after 3 to 8 days. Valganciclovir dosing is initiated on day 7 to 9 for 5 days. An approximately one week drug holiday follows. |
| Phase IA.3: Intratumoral Injection | Experimental | Drug: GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes)GEN2 is administered in repeating three week cycles. On week one, GEN2 is given via injection directly into the tumor lesions on one day and the presence of the HSV-TK-m2 expression is monitored by [18F]FHBG PET scanning after 3 to 8 days. Valganciclovir dosing is initiated on day 7 to 9 for 5 days. An approximately one week drug holiday follows. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
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 |
|---|---|---|
| GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes)GEN2 is an investigational drug combining cytotoxic and immunotherapy. | Drug | Phase 1A.1: Peripheral IV, Phase IA.2: Hepatic Artery Infusion, Phase IA.3: Intratumoral Injection |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: First 3 weeks of GEN2 Administration
The MTD is the defined as the highest dose level at which, at most, one patient experiences a DLT.
Dose Limiting Toxicity (DLT)
Time frame: First 3 weeks of GEN2 Administration
* Grade 4 neutropenia * Grade 4 thrombocytopenia; * Grade 3 or greater nausea and/or vomiting despite the use of adequate/maximal medical intervention and/or prophylaxis; * Any Grade 3 or greater non-hematological toxicity (except Grade 3 injection site reaction, alopecia, fatigue); * Retreatment delay of more than 3 weeks due to delayed recovery from a toxicity related to treatment with GEN2; * Grade 3 or greater allergic (hypersensitivity) reaction despite the appropriate use of premedications (defined within the CTC as "Prolonged" (e.g., not rapidly reponsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae (e.g., renal impairment, pulmonary infiltrates).
Recommended Phase 2 Dose (RP2D)
Time frame: First 3 weeks of GEN2 Administration
The RP2D will be administered for Phase 1B. It is determined when the accelerated phase ends for Phase IA and the dose assignment for a new patient in the standard dose escalation will follow a modified Fibonacci scheme. If a modified Fibonacci has already been used, the RP2D will be explored from the remaining intervals between the dose which had no DLTs and the Maximum Administered Dose (MAD).
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: Treatment Initiation until 30 days after last dose of GEN2
Each Adverse Event is to be classified by the Investigator as serious or non-serious. The classification of the gravity of the event determines the reporting procedures to be followed.
4 secondary outcomes
Plasma pharmacokinetics of GEN2
Time frame: During Week 1 of Cycle 1, Cycle 2 & Cycle 6 (each cycle is 28 days)
HSV-TK-m2 protein expression from GEN2 via serial [18F]FHBG PET and/or SPECT imaging
Time frame: Day 3-8 of GEN2 Treatment
Preliminary Evidence of anti-tumor activity of GEN2
Time frame: Week 9 and every 6 weeks thereafter through study completion, an average of 8 months.
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
Time frame: Cycle 1, Cycle 2, Cycle 6, after 6th month on treatment, annually thereafter
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2024.
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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. This study is not recruiting at the moment.
Priscilla B Caguioa, MD principal investigator
St. Luke's Medical Center - Quezon City
Maria Belen E Tamayo, MD principal investigator
Makati Medical Center
John P Querol, MD principal investigator
The Medical City
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes) in people with Hepatocellular Carcinoma and Metastatic Cancer, run by GenVivo, Inc. at 4 sites in Philippines.
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 14 inclusion and 9 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: finished, as of the sponsor's last update on 6 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Philippines. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: First 3 weeks of GEN2 Administration). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Nov 2024.