Ovarian Carcinoma
Conditions
Keywords
ovarian carcinoma, ovarian cancer, ovarian neoplasms, ovarian diseases
Brief summary
This study will evaluate NanoPac® administered intraperitoneally (IP) immediately post-cytoreductive surgery, followed by standard of care (SOC) intravenous (IV) chemotherapy, in women with ovarian cancer. The study will compare IP NanoPac® (plus IV chemotherapy) with SOC IV chemotherapy alone.
Detailed description
Research has shown that the administration of chemotherapy directly into the peritoneal cavity (intraperitoneal \[IP\] chemotherapy) may provide a significant survival benefit to women with ovarian cancer when combined with cytoreductive surgery and IV chemotherapy. This study will include a dose-finding phase and an efficacy phase to evaluate IP NanoPac® administered immediately post-cytoreductive surgery in women with ovarian cancer. In the dose-finding phase, subjects will be enrolled in dose-escalated cohorts of three subjects and receive IP NanoPac® at 100, 200, 300, or 400 mg/m2 plus standard of care (SOC) IV chemotherapy. Subjects will be followed for disease status for 12 months. The two best doses from the dose-finding phase will be determined. In the efficacy phase, subjects will be randomized 1:1:1 to one of the two best doses plus SOC IV chemotherapy or SOC alone.
Interventions
DRUGNanoPac® 100 mg/m2
Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment
DRUGNanoPac® 200 mg/m2
Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment
DRUGNanoPac® 300 mg/m2
Single intraperitoneal injection of 300 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment
DRUGNanoPac® 400 mg/m2
Single intraperitoneal injection of 400 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment
DRUGStandard of Care Intravenous Chemotherapy
Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment
Sponsors
US Biotest, Inc.
NanOlogy, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Epithelial ovarian cancer which is contained within the abdomen, but may include pleural effusion if that is the limit of non-peritoneal cavity disease. If subject has recurrent epithelial ovarian cancer, the disease must be platinum sensitive (recurrence \>6 months from prior chemotherapy regimen that included a platinum agent and cytoreductive surgery) * Subject appropriate for cytoreductive surgery and treatment with IV platinum and paclitaxel * Minimal or non-symptomatic ascites * ≥18 years old * Signed informed consent
Exclusion criteria
* Epithelial ovarian cancer outside of the peritoneal cavity, with the exception of pleural effusions * Anticipated use of concomitant chemotherapy (other than the protocol-specified agents), immunotherapy, or radiation therapy * Treatment with a prior investigational agent within 30 days of planned instillation of NanoPac®, with the exception of subjects participating in poly (ADP-ribose) polymerase (PARP) inhibitor trials. These subjects must discontinue the investigational agent prior to surgery * Known sensitivity to any of the study medication components or the chemotherapy regimen * History of prior malignancy other than ovarian that has not been in remission for \>5 years, with the exception of basal cell or squamous cell carcinoma or cervical carcinoma in situ on biopsy * Ileostomy or hepatic resection during current cytoreductive surgery * Women of childbearing potential not practicing adequate forms of birth control
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent Adverse Events | 12 months | Adverse events will include any clinically relevant changes in laboratory values, vital signs, and physical examination. Treatment-emergent adverse events occur when the date and time of the adverse event onset is on or after the first application of the investigational agent and any time up to when the intravenous chemotherapy commences. Treatment-emergent adverse events will be summarized for each treatment group. The summaries will include an overall summary of the number of subjects reporting and the number of events reported, summaries of adverse events leading to termination or death, and summaries by severity and relatedness (separately and combined). Of greatest interest will be post-surgery signs of toxicity (e.g., severe abdominal pain after 5-7 days, neutropenia, thrombocytopenia, bowel dehiscence, prolonged ileus). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration of Paclitaxel (Cmax) | 12 months | Plasma samples will be taken on Day 1 at 1, 2, 4, 8, and 24 hours post-intraperitoneal administration of NanoPac® and weekly thereafter until IV chemotherapy begins. Additionally, a pharmacokinetics (PK) sample will be collected from every subject prior to each cycle of IV chemotherapy for determination of paclitaxel concentrations to assess potential NanoPac® persistence. PK levels of paclitaxel in the plasma will be summarized descriptively. |
| Progression Free Survival (PFS) at 12 Months | 12 months post-treatment | Progression free survival (PFS) was assessed every 3 months until the end of the 12-month follow-up period, and every 6 months thereafter until progression or the last subject in the trial has completed 12 months of follow-up. Factors taken into account to determine time-to-progression included CA-125 levels, tumor burden as assessed by imaging and utilizing RECIST version 1.1 for assessment of response, and cancer-related symptoms such as bowel obstruction and ascites. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NanoPac® 100 mg/m2 Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.
NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment | 7 |
| NanoPac® 200 mg/m2 Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.
NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment | 3 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | NanoPac® 200 mg/m2 | NanoPac® 100 mg/m2 |
|---|---|---|---|
| Age, Continuous | 67 years | 62 years | 68 years |
| Disease Status Primary | 6 Participants | 2 Participants | 4 Participants |
| Disease Status Recurrent | 4 Participants | 1 Participants | 3 Participants |
| ECOG Status ECOG 0 | 7 Participants | 2 Participants | 5 Participants |
| ECOG Status ECOG 1 | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Female | 10 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Status of Ovarian Cancer at Screening IIIA2 | 1 Participants | 1 Participants | 0 Participants |
| Status of Ovarian Cancer at Screening IIIB | 2 Participants | 0 Participants | 2 Participants |
| Status of Ovarian Cancer at Screening IIIC | 5 Participants | 1 Participants | 4 Participants |
| Status of Ovarian Cancer at Screening IVB | 2 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 7 | 1 / 3 |
| other Total, other adverse events | 7 / 7 | 3 / 3 |
| serious Total, serious adverse events | 4 / 7 | 3 / 3 |
Outcome results
Primary
Treatment-emergent Adverse Events
Adverse events will include any clinically relevant changes in laboratory values, vital signs, and physical examination. Treatment-emergent adverse events occur when the date and time of the adverse event onset is on or after the first application of the investigational agent and any time up to when the intravenous chemotherapy commences. Treatment-emergent adverse events will be summarized for each treatment group. The summaries will include an overall summary of the number of subjects reporting and the number of events reported, summaries of adverse events leading to termination or death, and summaries by severity and relatedness (separately and combined). Of greatest interest will be post-surgery signs of toxicity (e.g., severe abdominal pain after 5-7 days, neutropenia, thrombocytopenia, bowel dehiscence, prolonged ileus).
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NanoPac® 100 mg/m2 | Treatment-emergent Adverse Events | 80 Treatment Emergent Adverse Events |
| NanoPac® 200 mg/m2 | Treatment-emergent Adverse Events | 28 Treatment Emergent Adverse Events |
Secondary
Maximum Plasma Concentration of Paclitaxel (Cmax)
Plasma samples will be taken on Day 1 at 1, 2, 4, 8, and 24 hours post-intraperitoneal administration of NanoPac® and weekly thereafter until IV chemotherapy begins. Additionally, a pharmacokinetics (PK) sample will be collected from every subject prior to each cycle of IV chemotherapy for determination of paclitaxel concentrations to assess potential NanoPac® persistence. PK levels of paclitaxel in the plasma will be summarized descriptively.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NanoPac® 100 mg/m2 | Maximum Plasma Concentration of Paclitaxel (Cmax) | 12.56 ng/mL | Standard Deviation 10.98 |
| NanoPac® 200 mg/m2 | Maximum Plasma Concentration of Paclitaxel (Cmax) | 26.50 ng/mL | Standard Deviation 13.56 |
Secondary
Progression Free Survival (PFS) at 12 Months
Progression free survival (PFS) was assessed every 3 months until the end of the 12-month follow-up period, and every 6 months thereafter until progression or the last subject in the trial has completed 12 months of follow-up. Factors taken into account to determine time-to-progression included CA-125 levels, tumor burden as assessed by imaging and utilizing RECIST version 1.1 for assessment of response, and cancer-related symptoms such as bowel obstruction and ascites.
Time frame: 12 months post-treatment
Population: Of the 10 subjects enrolled, four subjects were not evaluable for PFS at 12 months post-NanoPac instillation. For one subject, no imaging was performed over the course of the study; one subject was deceased due to leptomeningeal carcinomatosis; one subject was deceased due to a respiratory arrest; and one subject withdrew consent from the study. Both deaths were considered not related to study medication by the Investigator and the Medical Monitor.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NanoPac® 100 mg/m2 | Progression Free Survival (PFS) at 12 Months | PFS at 12 months | 4 Participants |
| NanoPac® 100 mg/m2 | Progression Free Survival (PFS) at 12 Months | Disease Progression | 0 Participants |
| NanoPac® 200 mg/m2 | Progression Free Survival (PFS) at 12 Months | PFS at 12 months | 0 Participants |
| NanoPac® 200 mg/m2 | Progression Free Survival (PFS) at 12 Months | Disease Progression | 2 Participants |