Feasibility Study of Intraperitoneal Paclitaxel
This is a single arm phase 2 trial evaluating the efficacy and tolerability of intraperitoneal paclitaxel with oxaliplatin and capecitabine in advanced gastric cancer patients with peritoneal metastasis and/or cancer cells on peritoneal cytology. Twenty patients will be recruited into the study for an estimated period of two years. Paclitaxel will be administered intraperitoneally at 40mg/m2 on Day 1 and 8 in patients receiving standard intravenous oxaliplatin 130mg/m2 on Day 1 and capecitabine 1000mg/m2 on day 1-14. The study hypothesizes that the addition of intraperitoneal paclitaxel with chemotherapy will improve treatment efficacy.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Feasibility Study of Intraperitoneal Paclitaxel With Oxaliplatin and Capecitabine in Patients With Advanced Gastric Cancer|
- Overall survival (OS) rate [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]The primary end point is 1-year survival because most patients may not have measurable disease, hence response rate and progression free survival are less easy to assess.
- Number of participants with adverse events [ Time Frame: 3-weekly ] [ Designated as safety issue: Yes ]Toxicity will be monitored 3-weekly and graded according to the National Cancer Institute —Common Terminology Criteria for Adverse Events version 4.0.
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||November 2015|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Experimental: IP Paclitaxel
Paclitaxel will be administered intraperitoneally at 40mg/m2 on Days 1 and 8 in a 21-day cycle in patients receiving intravenous oxaliplatin 100mg/m2 on Day 1 and capecitabine 1000mg/m2 twice daily on Days 1-14.
Drug: IP Paclitaxel
Each treatment cycle will consist of 21 days, with 14 days on treatment and 7 days off-treatment. Oxaliplatin will be administered intravenously (on Day 1 of each cycle). Paclitaxel will be administered intra-abdominally on Day 1 and Day 8 of each cycle. In particular, a needle will be inserted into the intraperitoneal injection port for normal saline to be injected intra-abdominally over one hour, followed by paclitaxel chemotherapy over a further one hour. Capecitabine will be taken by mouth from Day 1 to 14 of each cycle.
The median survival of patients with unresectable gastric cancer treated with systemic chemotherapy is about 12 months. In patients with histologically proven unresectable or recurrent gastric cancer limited to the peritoneum and/or cancer cells in peritoneal cytology, the combination of i.p. paclitaxel with systemic chemotherapy reported a median survival time of 23.6 months. The peritoneal cytology turned negative for 86% of patients. In an updated report, gastrectomy was performed on 52 patients after disappearance or obvious shrinkage of peritoneal metastasis. In this cohort, the median survival time (MST) was 34.9 months. A phase III trial (PHOENIX-GC trial (Phase III study of S-1 plus intravenous and intraperitoneal paclitaxel versus S-1 plus cisplatin for gastric cancer with peritoneal metastasis )) comparing intraperitoneal(IP) regimen with systemic chemotherapy versus systemic therapy alone is currently opened for recruitment in Japan.
The multidisciplinary treatment combining IP-containing chemotherapy and surgery was found to be safe and effective for gastric cancer patients with peritoneal metastasis. A phase I study combining i.p. paclitaxel with oxaliplatin and S-1, found no dose limiting toxicity in all dose levels. Grade 3 neutropenia was observed in one patient at recommended phase 2 dose (RP2D) of i.p. paclitaxel of 40 mg/m2. In addition, grade 2 non-hematological toxicities observed were anorexia (n=6/12), fatigue (n=4/12) and nausea (n=2/12).
Both S-1 and capecitabine are orally available fluoropyrimidine. When combined with oxaliplatin, both S-1 and capecitabine were found to be equally active and well tolerated in advanced gastric cancer patients. As S-1 is not yet widely available worldwide, the combination of capecitabine and a platinum chemotherapy is still one of the most commonly adopted chemotherapy regimen for patients with advanced gastric cancer. In this study, we intend to assess the efficacy and feasibility of combining weekly i.p. paclitaxel with oxaliplatin and capecitabine.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01739894
|Contact: Wei Peng Yong, MBBS||(65) 6779 5555||Wei_Peng_Yong@nuhs.edu.sg|
|Contact: Robert Lim, MBBS||(65) 6779 5555||Robert_Lim@nuhs.edu.sg|
|National University Hospital||Recruiting|
|Singapore, Singapore, 119074|
|Contact: Wei Peng Yong, MBBS (65) 6779 5555 Wei_Peng_Yong@nuhs.edu.sg|
|Contact: Maricel Cordero (65) 6772 2612 email@example.com|
|Principal Investigator: Wei Peng Yong, MBBS|
|Principal Investigator:||Wei Peng Yong, MBBS||National University Hospital, Singapore|