Back to resultsGEN2 Directed Cancer Immunotherapy Trial (GEN2)
Primary Purpose
Hepatocellular Carcinoma, Metastatic Cancer
Status
Recruiting
Phase
Phase 1
Locations
Philippines
Study Type
Interventional
Intervention
GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes)
Sponsored by
About this trial
This is an interventional other trial for Hepatocellular Carcinoma focused on measuring Liver Metastasis, Liver Cancer
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.
Sites / Locations
- Makati Medical CenterRecruiting
- The Medical CityRecruiting
- National Kidney and Transplant InstituteRecruiting
- St. Luke's Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Phase 1A.1: Peripheral IV
Phase IA.2: Hepatic Artery Infusion
Phase IA.3: Intratumoral Injection
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD)
The MTD is the defined as the highest dose level at which, at most, one patient experiences a DLT.
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).
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).
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.
Secondary Outcome Measures
Plasma pharmacokinetics of GEN2
GEN2 PK Cmax is dose proportional.
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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04313868
Brief Title
GEN2 Directed Cancer Immunotherapy Trial
Acronym
GEN2
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
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 13, 2014 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GenVivo, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Metastatic Cancer
Keywords
Liver Metastasis, Liver Cancer
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Dose Escalation Trial
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
122 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase 1A.1: Peripheral IV
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase IA.2: Hepatic Artery Infusion
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase IA.3: Intratumoral Injection
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GEN2 (HSV-Thymidine Kinase-m2 and hGM-CSF Genes)
Intervention Description
GEN2 is an investigational drug combining cytotoxic and immunotherapy.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
The MTD is the defined as the highest dose level at which, at most, one patient experiences a DLT.
Time Frame
First 3 weeks of GEN2 Administration
Title
Dose Limiting Toxicity (DLT)
Description
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).
Time Frame
First 3 weeks of GEN2 Administration
Title
Recommended Phase 2 Dose (RP2D)
Description
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).
Time Frame
First 3 weeks of GEN2 Administration
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
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.
Time Frame
Treatment Initiation until 30 days after last dose of GEN2
Secondary Outcome Measure Information:
Title
Plasma pharmacokinetics of GEN2
Description
GEN2 PK Cmax is dose proportional.
Time Frame
During Week 1 of Cycle 1, Cycle 2 & Cycle 6 (each cycle is 28 days)
Title
HSV-TK-m2 protein expression from GEN2 via serial [18F]FHBG PET and/or SPECT imaging
Description
Identify number of participants with positive [18F] FHBG scan
Time Frame
Day 3-8 of GEN2 Treatment
Title
Preliminary Evidence of anti-tumor activity of GEN2
Description
Measure of anti-tumor efficacy based on objective tumor assessments made according to the irRECIST 1.1
Time Frame
Week 9 and every 6 weeks thereafter through study completion, an average of 8 months.
Title
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
Description
No replication-competent retrovirus. No vector integration into genomic DNA of PBLS. No GM-CSF detectable in patients after GEN2 administration
Time Frame
Cycle 1, Cycle 2, Cycle 6, after 6th month on treatment, annually thereafter
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jennifer Olive Arellano
Phone
+63286571871
Email
jenny.arellano@novotech-cro.com
First Name & Middle Initial & Last Name or Official Title & Degree
Karl Bean
Phone
+1-626-768-5032
Email
kabean@genvivoinc.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Priscilla B Caguioa, MD
Organizational Affiliation
St. Luke's Medical Center - Quezon City
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Maria Belen E Tamayo, MD
Organizational Affiliation
Makati Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John P Querol, MD
Organizational Affiliation
The Medical City
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Necy S Juat, MD
Organizational Affiliation
National Kidney and Transplant Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Makati Medical Center
City
Makati City
ZIP/Postal Code
1229
Country
Philippines
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Belen Tamayo, MD
Phone
+632 8888 8999
Email
mabel_tamayo2003@yahoo.com
First Name & Middle Initial & Last Name & Degree
Regina E Dy, MD
First Name & Middle Initial & Last Name & Degree
Angelo Lozada, MD
Facility Name
The Medical City
City
Pasig City
Country
Philippines
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Querol, MD
Phone
+632 8988 1000
Email
docjohnq@yahoo.com
Facility Name
National Kidney and Transplant Institute
City
Quezon City
ZIP/Postal Code
1101
Country
Philippines
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Necy Juat, MD
Phone
+632 8981 0300
Email
necy_md@yahoo.com
First Name & Middle Initial & Last Name & Degree
Andrea Monica Espinosa, MD
Facility Name
St. Luke's Medical Center
City
Quezon City
ZIP/Postal Code
1112
Country
Philippines
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Priscilla B Caguioa, MD
Phone
+63287230101
Email
caguioapriscilla@yahoo.com
First Name & Middle Initial & Last Name & Degree
Rubi K Li, MD
First Name & Middle Initial & Last Name & Degree
JoanneMarie B Garcia, MD
12. IPD Sharing Statement
Learn more about this trial
GEN2 Directed Cancer Immunotherapy Trial
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