Phase II Study of Intraperitoneal NanoPac® in Patients With Ovarian Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Study of Four Dose Levels of Intraperitoneal NanoPac® Plus IV Carboplatin and Paclitaxel in Patients With Epithelial Ovarian Cancer Undergoing Cytoreductive Surgery

Conditions
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Ovarian Carcinoma

Intervention / Treatment
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* Drug: NanoPac® 100 mg/m2
* Drug: NanoPac® 200 mg/m2
* Drug: NanoPac® 300 mg/m2
* Drug: NanoPac® 400 mg/m2
* Drug: Standard of Care Intravenous Chemotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NanoPac® 100 mg/m2<br>Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. | Drug: NanoPac® 100 mg/m2<br>* Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment<br>Drug: Standard of Care Intravenous Chemotherapy<br>* Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment<br>|
| Experimental: NanoPac® 200 mg/m2<br>Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. | Drug: NanoPac® 200 mg/m2<br>* Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment<br>Drug: Standard of Care Intravenous Chemotherapy<br>* Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment<br>|
| Experimental: NanoPac® 300 mg/m2<br>Intraperitoneal NanoPac® 300 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. | Drug: NanoPac® 300 mg/m2<br>* Single intraperitoneal injection of 300 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment<br>Drug: Standard of Care Intravenous Chemotherapy<br>* Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment<br>|
| Experimental: NanoPac® 400 mg/m2<br>Intraperitoneal NanoPac® 400 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy. | Drug: NanoPac® 400 mg/m2<br>* Single intraperitoneal injection of 400 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment<br>Drug: Standard of Care Intravenous Chemotherapy<br>* Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment<br>|
| Active Comparator: Standard of Care Intravenous Chemotherapy<br>Standard of care intravenous chemotherapy (with platinum and taxane agents) administered per institutional standards. | Drug: Standard of Care Intravenous Chemotherapy<br>* Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 months | 
| 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. | 12 months post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian cancer, ovarian neoplasms, ovarian diseases, ovarian carcinoma