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Trial registered on ANZCTR


Registration number
ACTRN12614001063606
Ethics application status
Approved
Date submitted
16/07/2014
Date registered
3/10/2014
Date last updated
29/07/2019
Date data sharing statement initially provided
29/07/2019
Date results information initially provided
29/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
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
Scientific title
Phase I open label trial of the safety and tolerability of intraperitoneal paclitaxel in combination with intravenous cisplatin and oral capecitabine in patients with advanced gastric cancer and peritoneal metastases
Secondary ID [1] 285000 0
Nil
Universal Trial Number (UTN)
U1111-1159-3914
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Gastric Cancer 292505 0
Peritoneal metastases 292506 0
Condition category
Condition code
Cancer 292813 292813 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each Cycle will be 21 days and includes the following combination:
Capecitabine (oral) 1000 mg/m2 twice a day, day 1 to 14 every 21 days
Cisplatin at 80 mg/m2 day (IV), day 1 every 21 days
Intraperitoneal paclitaxel will be given by chemotherapy trained nursing staff on day 1 and day 8 of a 21 day cycle. The dose of paclitaxel will vary depending on the cohort


Cohort 1 10mg/m2
Cohort 2 20mg/m2
Cohort 3 30mg/m2

Patients will receive 6 cycles of chemotherapy unless unacceptable toxicity or progression of disease occurs.
Intervention code [1] 289833 0
Treatment: Drugs
Comparator / control treatment
single arm study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292671 0
Maximum tolerated dose of intraperitoneal paclitaxel, this will be assessed based on the number of patients who have experienced dose limiting toxicity
If no dose limiting toxicity is seen after 3 patients have completed treatment in Cohort 1, patients will commence enrolment into Cohort 2.

If no dose limiting toxicity is seen after 3 patients have completed treatment in Cohort 2, patients will commence enrolment into Cohort 3.

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.
Timepoint [1] 292671 0
maximum 6 cycles, each cycle is 3 weeks, equals a total of 18 weeks, plus any potential dose delays.
Secondary outcome [1] 309467 0
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)
Timepoint [1] 309467 0
6 cycles (approx. 18 weeks)
Secondary outcome [2] 309468 0
Overall response rate (based on RECIST 1.1 criteria)
Timepoint [2] 309468 0
6 cycles (approx. 18 weeks)
Secondary outcome [3] 309469 0
Ascites response (based on imaging)
Timepoint [3] 309469 0
measured from end of treatment and up to 2 years post registration on trial.
Secondary outcome [4] 309470 0
Overall survival
Timepoint [4] 309470 0
2 years post registration on trial.
Secondary outcome [5] 309471 0
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)
Timepoint [5] 309471 0
2 years post registration on trial.
Secondary outcome [6] 309472 0
Progression free survival
Timepoint [6] 309472 0
2 years post registration on trial.

Eligibility
Key inclusion criteria
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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 2724 0
Flinders Medical Centre - Bedford Park

Funding & Sponsors
Funding source category [1] 289614 0
Self funded/Unfunded
Name [1] 289614 0
Address [1] 289614 0
Country [1] 289614 0
Primary sponsor type
Individual
Name
A/Prof Chris Karapetis
Address
Flinders Medical Centre
Flinders Drive
Bedford Park
5042 SA
Country
Australia
Secondary sponsor category [1] 288300 0
None
Name [1] 288300 0
Address [1] 288300 0
Country [1] 288300 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303937 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 303937 0
Level 6
1 Flinders Drive
Bedford Park SA 5042
Ethics committee country [1] 303937 0
Australia
Date submitted for ethics approval [1] 303937 0
30/04/2014
Approval date [1] 303937 0
28/07/2014
Ethics approval number [1] 303937 0
189.14

Summary
Brief summary
This is a Phase I trial to determine safety and tolerability of paclitaxel in combination with cisplatin and capecitabine in patients with advanced gastric cancer and peritoneal metastases. Who is it for? You may be eligible to join this study if you are aged 18 years or above, have been diagnosed with gastric cancer and peritoneal metastases, and have not had previous chemotherapy for metastatic gastric cancer. Study details All participants will be given the combined treatment of paclitaxel, given through an intraperitoneal catheter (a thin tube surgically inserted through the stomach cavity), cisplatin, given intravenously (through a tube inserted into the vein), and capecitabine, given orally. Different doses will be tested to determine the maximum tolerated dose for paclitaxel. Participants will be follow-up for up to 6 cycles, or 18 weeks, during treatment and then for a further two years post treatment in order to determine safety and tolerability of paclitaxel, response rate, survival and effect of treatment on quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 50010 0
A/Prof Chris Karapetis
Address 50010 0
Flinders Medical Centre
Flinders Drive
Bedford Park
SA 5042
Country 50010 0
Australia
Phone 50010 0
+61 8 82048997
Fax 50010 0
Email 50010 0
chris.karapetis@health.sa.gov.au
Contact person for public queries
Name 50011 0
Miss Kelly Mead
Address 50011 0
Flinders Medical Centre
Flinders Drive
Bedford Park
SA 5042
Country 50011 0
Australia
Phone 50011 0
+61882046151
Fax 50011 0
Email 50011 0
kelly.mead@health.sa.gov.au
Contact person for scientific queries
Name 50012 0
Miss Kelly Mead
Address 50012 0
Flinders Medical Centre
Flinders Drive
Bedford Park
SA 5042
Country 50012 0
Australia
Phone 50012 0
+61882046151
Fax 50012 0
Email 50012 0
kelly.mead@health.sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
not in ethics approval
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary