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Trial registered on ANZCTR


Registration number
ACTRN12611000033943
Ethics application status
Approved
Date submitted
4/01/2011
Date registered
10/01/2011
Date last updated
3/02/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase II study of oxaliplatin/5-FU/Avastin and concurrent radiation in patients with simultaneous primary and metastatic rectal cancer
Scientific title
A phase II study of oxaliplatin/5-FU/Avastin and concurrent radiation to determine tolerability in patients with simultaneous primary and metastatic rectal cancer
Secondary ID [1] 253100 0
10/79 PMCC Protocol Number
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary rectal cancer 258659 0
Metastatic rectal cancer 258660 0
Condition category
Condition code
Cancer 258801 258801 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single arm study - Integrated preoperative radiotherapy and chemotherapy over 11 weeks.

Treatment: drugs

Oxaliplatin (given intravenously): day 1 of each of weeks 1, 6 and 11 100mg/m2 given; day 1 of each of weeks weeks 3 and 8, 85 mg/m2 given.

Flurouracil: day 1 of each of weeks 1, 6 and 11 400mg/m2 bolus, given intravenously followed on day 1 by continuous infusion 2.4 g/m2, over 46 hours; on days of radiotherapy during both weeks 3-5 and weeks 8-10 - continuous infusion 200mg/m2/day over 96 hours

Leucovorin (given intravenously): day 1 of each of weeks 1, 6 and 11 200mg/m2 given.

Bevacizumab (given intravenously): day 1 of each of weeks 1, 3, 5, 7, 9 and 11 - 5mg/kg

Treatment: Other

Radiation Therapy: in both weeks 3-5 and weeks 8-10 25.2Gy in 14 fractions over 2 weeks and 4 days. A total of 50.4 Gy in 1.8 Gy per fraction is given. The first 45 Gy is given to the pelvic volume and the final 5.4 Gy is given to a boost volume.
Intervention code [1] 257621 0
Treatment: Drugs
Intervention code [2] 257622 0
Treatment: Other
Comparator / control treatment
N/A
Control group
Uncontrolled

Outcomes
Primary outcome [1] 259694 0
Tolerability rate: the percentage of patients who are able to complete the planned treatment program and do not require a treatment break for toxicity.
Timepoint [1] 259694 0
End of the treatment program (11 weeks)
Secondary outcome [1] 266395 0
Dose intensity
Timepoint [1] 266395 0
End of the treatment program.
Secondary outcome [2] 266396 0
Toxicity rates: will be calculated from worst grades of toxicities, tabulated as frequencies by grade for each type
Timepoint [2] 266396 0
4 weeks after the end of the treatment program.
Secondary outcome [3] 266397 0
Tumour response: radiological and functional imaging response - measured separately by RECIST criteria (CT/MRI) and by PET criteria.
Timepoint [3] 266397 0
Early response (functional): prior to commencement of week 3 of treatment program; also 4 weeks after the end of the treatment program (radiological and functional).
Secondary outcome [4] 266398 0
Vascular response. Measured by DCE-MRI
Timepoint [4] 266398 0
Prior to commencement of week 3 of treatment program
Secondary outcome [5] 266399 0
Progression-free duration. Measured by PET or MRI/CT
Timepoint [5] 266399 0
Prior to commencement of week 3 of treatment program; 4 weeks after the end of the treatment program; 3 monthly for 2 years or as indicated by symptoms.
Secondary outcome [6] 266400 0
Overall survival
Timepoint [6] 266400 0
Followup 3 monthly for 2 years

Eligibility
Key inclusion criteria
1. Patients with previously untreated and pathologically proven adenocarcinoma of the rectum with distant metastasis who would benefit from combined local therapy and systemic chemotherapy.
2. Lower border of tumour must be within 15cm of anal verge.
3. Age >= 18 years.
4. Absolute neutrophil count >= 1.5 x 10^9/L, haemoglobin >= 90 g/L, platelet count >=100 x 10^9/L
5. ECOG performance status of <= 2
6. Adequate renal function: GFR >= 55 ml/min (using radioisotope renal scan or derived from serum creatinine using the Cockcroft-Gault formula).
7. Adequate hepatic function with serum total bilirubin < 1.5 x upper limit of normal range, ALT/AST < 2.5 x UNL in the absence of liver metastases, or < 5 x UNL in the presence of liver metastases, ALP < 2.5 x UNL in the absence of liver metastases, or < 5 x UNL in the presence of liver metastases
8. No symptomatic peripheral neuropathy >= grade 2.
9. Males or non-pregnant, non-lactating females. Female patients of childbearing potential, not surgically sterilized, must take adequate contraceptive measures.
10. Has provided written informed consent for participation in this trial
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior pelvic radiotherapy
2. Febrile intercurrent illness or infection.
3. Previous history of unstable angina
4. Cardiac arrhythmia which in the opinion of the investigator would compromise the safe delivery of protocol treatment
5. Acute coronary syndrome even if controlled with medication
6. Myocardial infarction within the last 12 months
7. Concurrent treatment with other anti-cancer therapy.
8. No medical co-morbidities that have the potential to be exacerbated by or contra-indicate therapy
a. Uncontrolled hypertension
b. Active bleeding disorders within the last 3 months
c. Patients with NYHA Grade III/IV cardiac problems (e.g. congestive heart failure, or myocardial infarction or active myocardial ischemia within 12 months of study)
d. Patients with active liver disease (e.g., chronic active hepatitis, cirrhosis).
e. Patients with a known diagnosis of human immunodeficiency virus (HIV) infection.
f. Patients who have had major surgery within 28 days prior to commencing study drugs
g. Patients with a serious non-healing wound, ulcer or bone fracture

9. Significant medical condition which in the opinion of the investigator would compromise the planned delivery of the chemotherapy and radiotherapy or which may be potentially exacerbated by these modalities.
10. Locally recurrent rectal cancer
11. Female patients who are pregnant or breast-feeding
12. Medical or psychiatric conditions that compromises the patient's ability to give informed consent or to complete the protocol, or a history of non-compliance

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)
A participating site contacts the Trial Coordinating Centre to enrol a patient. After establishing that the site investigator has confirmed all eligibility criteria have been met, a unique registration number is allocated. Written confirmation of registration containing the registration number, patient initials and date of registration is sent to the site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
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)
Recruitment postcode(s) [1] 3469 0
3002
Recruitment postcode(s) [2] 3470 0
3128

Funding & Sponsors
Funding source category [1] 258116 0
Commercial sector/Industry
Name [1] 258116 0
Roche Products Pty Limited
Address [1] 258116 0
4-10 Inman Rd,
DEE WHY NSW 2099
Country [1] 258116 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
St Andrew's Place
East Melbourne,
Victoria, 3002
Country
Australia
Secondary sponsor category [1] 257295 0
None
Name [1] 257295 0
Address [1] 257295 0
Country [1] 257295 0
Other collaborator category [1] 251672 0
Hospital
Name [1] 251672 0
Box Hill Hospital
Address [1] 251672 0
Nelson Road
Box Hill,
Victoria, 3128
Country [1] 251672 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260208 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 260208 0
St Andrews Place
East Melbourne
Victoria, 3002
Ethics committee country [1] 260208 0
Australia
Date submitted for ethics approval [1] 260208 0
Approval date [1] 260208 0
16/12/2010
Ethics approval number [1] 260208 0
HREC/10/PMCC/11

Summary
Brief summary
This study looks at the tolerability and effectiveness of an 11 week program of integrated radiotherapy and chemotherapy with oxaliplatin, 5-flurouracil (5-FU), folinic acid and the agent bevacizumab in patients with simultaneous primary and metastatic adenocarcinoma of the rectum (back passage)
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31904 0
A/Prof Michael Michael
Address 31904 0
Peter MacCallum Cancer Centre St Andrew's Place East Melbourne Victoria, 3002
Country 31904 0
Australia
Phone 31904 0
+61 3 96561701
Fax 31904 0
+61 3 96561408
Email 31904 0
Michael.Michael@petermac.org
Contact person for public queries
Name 15151 0
Ms Marijana Vanevski
Address 15151 0
Centre for Biostatistics and Clinical Trials
Peter MacCallum Cancer Centre
St Andrew's Place
East Melbourne
Victoria, 3002
Country 15151 0
Australia
Phone 15151 0
+61 3 9656 1266
Fax 15151 0
Email 15151 0
Marijana.Vanevski@petermac.org
Contact person for scientific queries
Name 6079 0
A/Prof Assoc Prof Sam Ngan
Address 6079 0
Peter MacCallum Cancer Centre
St Andrew's Place
East Melbourne
Victoria, 3002
Country 6079 0
Australia
Phone 6079 0
+61 3 9656 1111
Fax 6079 0
Email 6079 0
Sam.Ngan@petermac.org

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary