Colorectal Carcinoma, CRC
Conditions
Keywords
Vaccinia, Vaccinia Virus, JX-594, Jennerex, Colorectal Carcinoma, Colorectal cancer, Colon Cancer, Rectal Cancer, oncolytic virus, viral therapy, RAS mutant, Erbitux failure, Oxaliplatin failure, FOLFOX failure, FOLFIRI failure, Irinotecan failure, Pexa-Vec
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of JX-594 (Pexa-Vec) administered intravenously either alone or in combination with Irinotecan in colorectal carcinoma patients who are refractory to or intolerant to standard therapy.
Detailed description
This was a Phase 1/2a, open-label, dose-escalation study in patients with advanced colorectal cancer (CRC)
Interventions
BIOLOGICALJX-594
Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
DRUGIrinotecan
180 mg/m2 IV every 2 weeks.
Sponsors
Jennerex Biotherapeutics
Transgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically-confirmed, advanced metastatic colorectal cancer failed treatment with fluoropyrimidine (fluoruracil or capecitabine) and oxaliplatin based therapies or had contradictions to treatment with these drugs as determined by the investigator * Failed treatment with irinotecan * Kras mutant tumor or Kras wild-type having failed cetuximab (Erbitux) or panitumumab (Vectibix) or had contradictions to treatment * Regorafenib-naïve (have not received regorafenib) * Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2 * Measurable tumor (≥1 cm longest diameter) * Acceptable health status as determined by the investigator and blood work (Chemistry, Complete Blood Count, Coagulation)
Exclusion criteria
* Intolerant to Irinotecan (if assigned to the combination arm: Cohort 3, Cohort 4 or Combination Expansion Arm) * Treatment with ketoconazole, enzyme-inducing anticonvulsants and St. John's Wort (if assigned to combination arm) * Significant immunodeficiency due to underlying illness and/or medication * History of severe exfoliative skin condition requiring systemic therapy within the past 2 years * Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural effusions * Active cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months * Viable Centrual Nervous System (CNS) malignancy associated with clinical symptoms * Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks for mitomycin c or nitrosoureas) * Prior participation in any other research protocol involving an investigational medicinal product within 4 weeks prior to first treatment * Use of prohibited anti-viral medication, interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be discontinued within 14 days prior to any JX 594 dose * Inability to suspend treatment with anti-hypertensive medication for 48 hours prior to and 48 hours after all JX-594 treatments. * Pregnant or nursing an infant * Diagnosis of chronic inflammatory bowel disease and/or bowel obstruction.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine Radiographic Response Rate of Patients Enrolled in the Phase 2a Portion of the Study | Scans every 8 weeks until progression, assessed up to 25 months | Percentage of participants with overall response (CR+PR) during the study per mRECIST 1.1. CR: disappearance of enhancing area; PR: \>=30% decrease in sum of enhancing area diameters. Per mRECIST 1.1, an objective response at week 8 must be confirmed by a subsequent scan to be classified as an overall response during the study. If a participant achieved a response at week 8, but the response was not confirmed at the subsequent visit, then the participant may be included in the 'ORR at Week 8 (CR+PR)' Row, but may not be included in the 'ORR During the study (CR+PR)' Row. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | CT scans every 8 weeks until progression, assessed up to 25 months | PFS (based on mRECIST) as determined by Independent Central Review is summarized for the ITT Population. |
| Overall Survival | Monthly until Death or Lost-to-Followup, assessed up to 25 months | Compare overall survival time of patients treated with JX-594 alone or in combination with irinotecan |
Countries
Canada, France, United States
Contacts
STUDY_DIRECTORJames Burke, MD
Jennerex Biotherapeutics
PRINCIPAL_INVESTIGATORDerek Jonker, MD
Ottawa Hospital and Research Institute
Participant flow
Recruitment details
Of the 66 patients screened, 52 patients were enrolled into the study. For the ITT Population, 3 patients were enrolled in Cohort 1, 24 patients were enrolled in Cohort 2, 5 patients were enrolled in Cohort 3, and 20 patients were enrolled in Cohort 4 (Pexa-Vec 1 x 109 pfu + irinotecan). Two patients (1 patient each in Cohorts 2 and 4) had pre-dosing AEs that led to discontinuation from the study prior to receiving treatment and were therefore excluded from the safety population and the PPP.
Participants by arm
| Arm | Count |
|---|---|
| Single Agent_ Cohort 1 JX-594 administered intravenously weekly for 5 weeks followed by up to 3 additional intravenous infusion boosts.
JX-594 3 x 10\^8 pfu, Days 1, 8,15, 22, and 29 | 4 |
| Single Agent_Cohort 2 JX-594 administered intravenously weekly for 5 weeks followed by up to 3 additional intravenous infusion boosts.
JX-594 1 x 10\^9 pfu, Days 1, 8,15, 22, and 29 | 25 |
| Combination_Cohort 3 JX-594 administered intravenously weekly for 5 weeks followed by up to three additional intravenous infusion boosts in combination with Irinotecan administered every 14 days beginning at Day 9.
JX-594 3 x 10\^8 pfu Day 1,8, 15, 22, 29 + irinotecan 180 mg/m2 biweekly starts on Day 9. | 4 |
| Combination_Cohort 4 JX-594 administered intravenously weekly for 5 weeks followed by up to three additional intravenous infusion boosts in combination with Irinotecan administered every 14 days beginning at Day 9.
JX-594 1 x 10\^9 pfu Day1, 8, 15, 22, 29 + irinotecan 180 mg/m2 biweekly starts on Day 9. | 17 |
| Total | 50 |
Baseline characteristics
| Characteristic | Total | Combination_Cohort 4 | Combination_Cohort 3 | Single Agent_ Cohort 1 | Single Agent_Cohort 2 |
|---|---|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 11.05 | 58.6 years STANDARD_DEVIATION 10.42 | 58.8 years STANDARD_DEVIATION 13.74 | 64.3 years STANDARD_DEVIATION 8.06 | 58.3 years STANDARD_DEVIATION 11.84 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 15 Participants | 4 Participants | 4 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 44 Participants | 11 Participants | 4 Participants | 4 Participants | 25 Participants |
| Sex: Female, Male Female | 20 Participants | 6 Participants | 1 Participants | 0 Participants | 13 Participants |
| Sex: Female, Male Male | 30 Participants | 11 Participants | 3 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 24 / 24 | 5 / 5 | 19 / 20 |
| other Total, other adverse events | 4 / 4 | 25 / 25 | 4 / 4 | 17 / 17 |
| serious Total, serious adverse events | 2 / 4 | 10 / 25 | 1 / 4 | 8 / 17 |
Outcome results
Primary
Determine Radiographic Response Rate of Patients Enrolled in the Phase 2a Portion of the Study
Percentage of participants who showed overall response during their participation in the study. Per Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) and assessed by tri-phasic contrast enhanced CT: Complete Response (CR), Disappearance of intratumoral enhancing area; Partial Response (PR), \>=30% decrease in the sum of the diameters of enhancing area; Overall Response (OR) = CR + PR.
Time frame: Scans Every 8 weeks until radiographic progression was confirmed by the site.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Agent_ Cohort 1 | Determine Radiographic Response Rate of Patients Enrolled in the Phase 2a Portion of the Study | 0 Participants |
| Single Agent_Cohort 2 | Determine Radiographic Response Rate of Patients Enrolled in the Phase 2a Portion of the Study | 0 Participants |
| Combination_Cohort 3 | Determine Radiographic Response Rate of Patients Enrolled in the Phase 2a Portion of the Study | 0 Participants |
| Combination_Cohort 4 | Determine Radiographic Response Rate of Patients Enrolled in the Phase 2a Portion of the Study | 1 Participants |