Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Carcinomatosis
Conditions
Keywords
Olvi-Vec, oncolytic virus, virotherapy, Viral therapy, immunotherapy, immune therapy, vaccinia, vaccinia virus, Genelux, ovarian cancer, platinum resistant, platinum refractory, peritoneal carcinomatosis, fallopian cancer, cancer, abdominal cancer, imaging, carcinoma, DNA virus, neoplasms, neoplasms by histological type, neoplasms, Glandular and Epithelial, Poxviridae infections, Virus diseases, recurrent ovarian cancer, intermediate platinum-sensitive
Brief summary
The purpose of this study is to determine if Olvi-Vec oncolytic immunotherapy is well tolerated with anti-tumor activity in patients diagnosed with recurrent or refractory ovarian cancer and peritoneal carcinomatosis.
Detailed description
Ovarian cancer (OC) remains the most lethal gynecologic malignancy owing to late detection, intrinsic and acquired chemo-resistance and remarkable heterogeneity. There is an unmet medical need to develop new therapy modalities. In preclinical studies, Olvi-Vec, has shown the ability to preferentially locate, colonize and destroy tumor cells in more than 30 different human tumors, including ovarian cancer. Olvi-Vec has been investigated in early stage clinical trials in the United States and Europe via systemic delivery as monotherapy and in combination with other therapies, and via regional delivery as monotherapy. Olvi-Vec treatment was well tolerated across different malignancies, routes of administration, and monotherapy as well as combination therapy protocols. The ability of Olvi-Vec to infect tumor tissue and kill tumor cells was demonstrated. In addition, virus-induced immune activation and favorable anti-tumor immune response have been observed. Evidences of anti-tumor efficacy and clinical benefits have also been documented.
Interventions
BIOLOGICALOlvi-Vec
Olvi-Vec is a genetically-engineered oncolytic vaccinia virus, which is administered via intraperitoneal infusion as multiple doses.
DRUGPlatinum-doublet with or without bevacizumab
Carboplatin + choice of non-platinum chemotherapy drug: taxane, paclitaxel, nab-paclitaxel, gemcitabine or doxorubicin pegylated liposomal with or without bevacizumab.
Sponsors
Genelux Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are enrolled in the open cohort at the time of study entry.
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed, written informed consent. * High-grade serous (including Malignant Mixed Mullerian Tumor (MMMT) with metastasis that contains high grade epithelial carcinoma), endometrioid, or clear-cell ovarian cancer which includes: (1) platinum-resistant (recurrence or progression in \< 6 months) or (2) platinum-refractory (progression while on platinum-based therapy); patient must have failed either at least 2 consecutive therapies or are not eligible for additional cytotoxic therapies (exception is Phase 2 receiving chemotherapy with/without bevacizumab). * Intermediate platinum-sensitive patients (recurrence of disease 6 to 12 months from last platinum compound treatment): Recurrent ovarian carcinoma with at least four prior individual treatment regimens including at least two separate platinum-based therapies with recurrence from the last platinum-based regimen less than 12 months, who are unwilling or unable to undergo additional platinum-based cytotoxic therapy (this sub-population is not applicable for Phase 2 receiving chemotherapy with/without bevacizumab). * Performance status ECOG is at 0 or 1, and life expectancy of 6 months * Has either measurable disease in the peritoneal cavity as defined by RECIST 1.1 (Phase 1b \& 2) or has non-measurable disease in the peritoneal cavity (Phase 1b) and can be confirmed by laparoscopy and/or elevated CA-125. Patients who have non-measurable disease that is not identifiable by PET/PET-CT scan, but who have elevated CA-125, and/or ascites, with visible disease confirmed by laparoscopy are also eligible. * Able to undergo IP injection. * Adequate renal, hepatic, bone marrow and immune functions. * Baseline tumor biopsy is required. * Documented progressive disease status at baseline (Phase 2).
Exclusion criteria
* Tumors of mucinous subtypes, or non-epithelial ovarian cancers (e.g., Brenner tumors, Sex-cord tumors). * Unresolved bowel obstruction. * Known central nervous system (CNS) metastasis. * Known seropositivity for HIV or active hepatitis infection. * History of thromboembolic event within the last 3 months. * Pregnant or breast-feeding women. * Smallpox vaccination within 1 year of study treatment. * Clinically significant cardiac disease. * Received prior gene therapy or therapy with cytolytic virus of any type. * Receiving concurrent antiviral agent active against vaccinia virus. * Have known allergy to ovalbumin or other egg products. * Have clinically significant dermatological disorders (e.g., eczema, psoriasis, or unhealed skin wounds or ulcers) as assessed by the Investigator. * Symptomatic malignant ascites and non-manageable pleural effusion. * Known hypersensitivity to bevacizumab, uncontrolled hypertension, history of stroke, or clinical findings suggestive of excessive risk for GL perforation (uncontrolled peptic ulcer disease, partial small bowel obstruction, etc.) that would make risks of bevacizumab unacceptable in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Related Treatment-emergent Adverse Event [Safety and Tolerability] (Phase 1b) | Change from baseline during Treatment and for 30 days following last dose over average of 2 years. | Determine safety and tolerability of administering 2 consecutive doses of Olvi-Vec via intraperitoneal catheter by the evaluation of the number of participants with related treatment-emergent adverse events (type, frequency, and severity) as assessed by CTCAE 4.03. |
| Progression-free Survival Following Treatment in Participants Enrolled in the Phase 2 Portion of Study With Platinum-resistant or Platinum-refractory Ovarian Cancer. | For participants enrolled in the Phase 2 portion, outcome is from the date of starting chemotherapy until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to 24 months. | Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Overall Response Rate (ORR) by Tumor Marker Cancer Antigen-125 (CA-125) for Participants Enrolled in the Phase 2 Portion of Study With Platinum-resistant or Platinum-refractory Ovarian Cancer | Assessed pre-treatment, during treatment at 2- to 3-week intervals and post-treatment assessed up to 24 months. | To assess anti-tumor response by Overall Response Rate by Tumor Marker Cancer Antigen-125 (CA-125) for participants who were enrolled in the Phase 2 portion of this study with platinum-resistant or platinum-refractory ovarian cancer. |
| Overall Response Rate (ORR) by RECIST 1.1 for Participants Enrolled in the Phase 2 Portion of the Study With Platinum-resistant or Platinum-refractory Ovarian Cancer | For evaluable participants enrolled in the Phase 2 portion of this study with platinum-resistant or platinum-refractory ovarian cancer who were assessed at pre-treatment, during treatment at 6- to 12-week intervals and post-treatment up to 24 months. | To assess anti-tumor response by Overall Response Rate (ORR) defined as disease control rate (DCR = CR + PR + SD≥15 weeks) by RECIST 1.1 criteria: Complete Response (CR) is a disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to quality for progressive disease; Progressive Disease (PD) is at least a 20% increase in sum of longest diameter of target lesions, with an absolute increase of at least 5 mm, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Tumor Response to Treatment for Participants Enrolled in the Phase 1b Portion of This Study | Assessed post-treatment at 6 to 12 week intervals or until disease progression or death from any cause, whichever comes first, assessed up to 24 months. | Participants enrolled in the Phase 1b study were assessed for best overall response to treatment with therapeutic intent by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. criteria: Complete Response (CR) is a disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to quality for progressive disease; Progressive Disease (PD) is at least a 20% increase in sum of longest diameter of target lesions, with an absolute increase of at least 5 mm, or the appearance of new lesions. |
| CA-125 Response in Participants Enrolled in the Phase 1b Portion of This Study | Assessed pre-treatment, during treatment and post-treatment at 6 to 12 week intervals, assessed up to 24 months. | CA-125 according to the Gynecologic Cancer Intergroup (GCIG) is measured by at least a 50% reduction in CA-125 levels from pre-treatment sample which is confirmed and maintained for at least 28 days. Pre-treatment CA-125 sample must be at least twice the upper limit of normal and obtained within 2 weeks prior to starting treatment. |
| Determine Progression-free Survival Following Treatment (Phase 1b) | From the date of starting chemotherapy until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to 24 months. | To assess the number of months of progression-free survival (PFS) by RECIST 1.1. |
| Overall Survival | By medical chart review until death or 3 years from the date of last treatment whichever comes first. | To determine overall survival (OS) in the participant population. |
| Clinical Benefit Rate | Approximately 24 months | Defined as the percentage of patients who have achieved CR + PR + SD by RECIST 1.1. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 2 clinical sites in the United States. Enrollment into cohorts based on order of consented and eligible participants into an open cohort.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Platinum Disease Intermediate platinum-sensitive ovarian cancer | 0 Participants |
| Platinum Disease Platinum-refractory ovarian cancer | 17 Participants |
| Platinum Disease Platinum-resistant ovarian cancer | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 43 Participants |
| Region of Enrollment United States | 46 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 6 | 5 / 5 | 1 / 1 | 22 / 22 | 11 / 12 |
| other Total, other adverse events | 5 / 6 | 5 / 5 | 1 / 1 | 22 / 22 | 11 / 11 |
| serious Total, serious adverse events | 2 / 6 | 1 / 5 | 0 / 1 | 5 / 22 | 2 / 11 |
Outcome results
None listed