Phase I open label trial of intraperitoneal paclitaxel in combination with intravenous cisplatin and oral capecitabine in patients with advanced gastric cancer and peritoneal metastases
- Conditions
- Advanced Gastric CancerPeritoneal metastasesCancer - Stomach
- Registration Number
- ACTRN12614001063606
- Lead Sponsor
- A/Prof Chris Karapetis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 15
1.Age greater than or equal to 18 years
2.A diagnosis of Gastric cancer proven by histopathology and either:
Biopsy proven peritoneal metastases OR
Cytology consistent with malignant ascites: in which case patient must have greater than or equal to 1 area of metastasis apart from the ascites.
3. Subject must not have received previous chemotherapy for metastatic gastric cancer
Previous adjuvant chemotherapy for gastric cancer is allowed
4.Adequate bone marrow function (platelets > 100 x 109/L, ANC > 1.5 x 109/L, P)
5.Adequate liver function (Serum bilirubin less than or equal to 1.5 ULN and ALT and ALP less than or equal to 3 ULN,)
6.Adequate renal function (Serum creatinine less than or equal to 1.5 UNL or creatinine clearance (CRCL) greater than or equal to 50ml/min (using Cockcroft-Gault Equation) )
7.negative pregnancy test if of potential child bearing age
8.Eastern Cooperative Oncology Group Performance Score (ECOG PS) 0, 1 or 2
9.Staging CT scan of chest/abdomen/pelvis within 30 days of registration
10.Study treatment both planned and able to start within 30 days of registration
11.Willing and able to comply with all study requirements, including treatment (able to swallow tablets), and required assessments
12.Signed, written informed consent
1.Contraindications to investigational chemotherapy regimen including allergies to any of the chemotherapy medications
2.Specific comorbidities or conditions
3.Other, for example those compromising the ability to assess key outcomes
4.Life expectancy of less than 3 months.
5.History of another malignancy within 5 years prior to registration. Patients with a past history of adequately treated cervical carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 5 years after definitive primary treatment.
6. Significant intercurrent illness that will interfere with the chemotherapy during the trial such as:
a. Known Human Immunodeficiency Virus (HIV) infection
b. Active infection
c. Myocardial infarction within the previous 6 months or significant cardiac disease resulting in an inability to tolerate the intravenous fluid load as required for administration of cisplatin
d. Severe lung disease which in the investigators opinion would limit the patient’s ability to tolerate large volumes of intra-abdominal fluids.
7. Peripheral neuropathy of any grade (based on NCI CTC version 4.0)
8. Clinically significant sensori-neural hearing impairment or tinnitus which may be exacerbated by cisplatin (Audiometric abnormalities without corresponding clinical deafness will not be grounds for exclusion).
9. Previous abdominal or pelvic radiation treatment.
10. Significant intra-abdominal adhesions as determined by the surgeon at time of staging laparoscopy.
11. Active intra-abdominal sepsis
12.Medical or psychiatric condition that compromises the ability of patients to give informed consent.
13.Pregnancy, lactation, or inadequate contraception. Women must be postmenopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a barrier method of contraception during treatment and for the subsequent three months after treatment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Maximum tolerated dose of intraperitoneal paclitaxel, this will be assessed based on the number of patients who have experienced dose limiting toxicity<br>If no dose limiting toxicity is seen after 3 patients have completed treatment in Cohort 1, patients will commence enrolment into Cohort 2. <br><br>If no dose limiting toxicity is seen after 3 patients have completed treatment in Cohort 2, patients will commence enrolment into Cohort 3. <br><br>If no dose limiting toxicity is seen after 3 patients have completed treatment in Cohort 3, this cohort will be expanded to 6 patients if maximum tolerated does (MTD) has not been reached. There will be no further dose escalation after Cohort 3.<br>[maximum 6 cycles, each cycle is 3 weeks, equals a total of 18 weeks, plus any potential dose delays.]
- Secondary Outcome Measures
Name Time Method The safety and tolerability of IP paclitaxel in combination with cisplatin and capecitabine (Rates of toxicities based on CTCAE 4.0 and also Rates of catheter complications)[6 cycles (approx. 18 weeks)];Overall response rate (based on RECIST 1.1 criteria)[6 cycles (approx. 18 weeks)];Ascites response (based on imaging)[measured from end of treatment and up to 2 years post registration on trial.];Overall survival[2 years post registration on trial.];Effects of treatment on quality of life. (based on average scores for aspects of HRQL during treatment as assessed by the FACT-Ga (Version 4) and EORTC STO22)[2 years post registration on trial.];Progression free survival[2 years post registration on trial.]