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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01289821




Registration number
NCT01289821
Ethics application status
Date submitted
3/02/2011
Date registered
4/02/2011
Date last updated
15/03/2017

Titles & IDs
Public title
First Line Treatment of Metastatic Colorectal Cancer With mFOLFOX6 in Combination With Regorafenib
Scientific title
An Uncontrolled, Open-label, Phase II Study in Subjects With Metastatic Adenocarcinoma of the Colon or Rectum Who Are Receiving First Line Chemotherapy With mFOLFOX6 (Oxaliplatin/ Folinic Acid/5-fluorouracil [5-FU]) in Combination With Regorafenib
Secondary ID [1] 0 0
2010-020121-41
Secondary ID [2] 0 0
11728
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Regorafenib (Stivarga, BAY73-4506)
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - Folinic acid
Treatment: Drugs - 5-FU (mFOLFOX6)

Experimental: Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6) - On Day 1, participants received 85 mg/m^2 oxaliplatin as a 2-hour intravenous (IV) infusion and folinic acid (either 400 mg/m^2 D/L-folinic acid or 200 mg/m^2 L-folinic acid) as a 2-hour IV infusion. Once the initial infusion was completed, participants received 5-FU 400 mg/m^2 IV bolus injection immediately followed by a 5-FU 2400 mg/m^2 IV infusion for 46 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17. Participants received Regorafenib (Stivarga, BAY73-4506) 160 mg orally (po) once daily (qd) on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days.


Treatment: Drugs: Regorafenib (Stivarga, BAY73-4506)
Subjects will receive regorafenib 160 mg od on days 4 to 10 and days 18 to 24 as four 40 mg coprecipitate tablets. In case of administration as a single agent during the study, regorafenib will be administered 160 mg od for 3 weeks on/1 week off. Each cycle consists of 28 days.

Treatment: Drugs: Oxaliplatin
On day 1 and day 15 of each cycle, participants will receive 85 mg/m^2 oxaliplatin as a 2 hour i.v. infusion.

Treatment: Drugs: Folinic acid
On day 1 and day 15 of each cycle, participants will receive folinic acid (either 400 mg/m^2 D/L-folinic acid or 200 mg/m^2 L-folinic acid) as a 2 hour i.v. infusion.

Treatment: Drugs: 5-FU (mFOLFOX6)
Participants will receive a 400 mg/m^2 5 FU i.v. bolus injection immediately followed by a 2400 mg/m^2 5 FU 46 hour i.v. infusion.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response (OR) - OR was defined as the best tumor response (confirmed complete response [CR] or partial response [PR]) observed by MRI or CT scan assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1. CR and PR were confirmed not earlier than 4 weeks following the initial detection of response. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). Any pathological lymph nodes (whether target or non target) must have a reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing nontarget lesions and no appearance of new lesions.
Timepoint [1] 0 0
From start of treatment until 30 days after termination of study medication, an average of 47 weeks. Assessed every 8 weeks.
Secondary outcome [1] 0 0
Overall Survival (OS) - OS was calculated as the time from first date of receiving study treatment to date of death due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up.
Timepoint [1] 0 0
From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Secondary outcome [2] 0 0
Progression-free Survival (PFS) - PFS was defined as time from the date of start of study treatment to the date of first observed disease progression (radiological according to central assessment or clinical), or death due to any cause, if death occurred before progression was documented. PFS for participants without disease progression or death at the date of database cutoff were right-censored at the last date of tumor assessment. Participants who had no tumor evaluation after baseline and no clinical progression post baseline and who did not die were censored at Day 1 in the analysis. PD = At least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non target lesions or the appearance of one or more new lesions will also constitute PD.
Timepoint [2] 0 0
From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Secondary outcome [3] 0 0
Disease Control (DC) - DC was defined as the proportion of participants who had a best response rating of CR, PR, or stable disease (SD) according to RECIST criteria that was achieved during treatment or within 30 days after termination of study treatment. CR and PR were confirmed not earlier than 4 weeks following the initial detection of response. A minimum of 8 weeks (allowing a minus 7-day time window) between start of study treatment and the first follow-up tumor assessment with SD as response was required to assign SD as best overall response.
Timepoint [3] 0 0
From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Secondary outcome [4] 0 0
Duration of Response (DOR) - DOR was defined as the time from the date of first documented objective response of PR or CR, whichever was noted earlier, to first subsequent disease progression or death (if death occurred before progression was documented). DOR was defined for responders only (that is, subjects with CR or PR). DOR for subjects without disease progression or death before progression was right censored at the date of their last tumor assessment.
Timepoint [4] 0 0
From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Secondary outcome [5] 0 0
Duration of Stable Disease (DOSD) - DOSD was only evaluated in participants failing to achieve a best response of CR or PR, but who achieved SD. DOSR was defined as the time (in days) from date of start of study treatment to the date at which disease progression or death (if death occurred before progression was first documented). The date the tumor scan was performed was used for this calculation. DOSD for participants without disease progression or death before progression at the time of analysis were censored at the date of their last tumor assessment.
Timepoint [5] 0 0
From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks

Eligibility
Key inclusion criteria
- Male or female subjects aged = 18 years

- Histological or cytological documentation of adenocarcinoma of the colon or rectum

- Suitable to receive mFOLFOX6 regimen as first line metastatic treatment

- At least 1 measurable lesion as per RECIST version 1.1

- Unresectable or unlikely becoming resectable metastatic disease

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Life expectancy of at least 3 months

- Adequate bone marrow, liver, and renal function
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior systemic anticancer therapy for metastatic colorectal cancer (CRC). Adjuvant
chemotherapy for CRC (Stage I, II, III) is permitted, if the adjuvant therapy ended >
6 months before screening and recurrent disease was documented.

- Prior treatment with antivascular endothelial growth factor (anti-VEGF) agents and any
signal transduction inhibitors (STIs)

- Uncontrolled hypertension

- Subjects with symptoms, signs, or history of brain metastases

- Any hemorrhage or bleeding event = Common Terminology Criteria for Adverse Events
(CTCAE) Grade 3 within 4 weeks of start of study treatment

- Sensory neuropathy (> CTCAE Grade 1), unresolved toxicity > CTCAE Grade 1 attributed
to any prior therapy/procedure excluding alopecia

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
NSW,SA
Recruitment hospital [1] 0 0
- Concord
Recruitment hospital [2] 0 0
- Woodville South
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles - Brussel
Country [3] 0 0
Belgium
State/province [3] 0 0
Edegem
Country [4] 0 0
Belgium
State/province [4] 0 0
Leuven
Country [5] 0 0
Germany
State/province [5] 0 0
Baden-Württemberg
Country [6] 0 0
Germany
State/province [6] 0 0
Niedersachsen
Country [7] 0 0
Germany
State/province [7] 0 0
Nordrhein-Westfalen
Country [8] 0 0
Germany
State/province [8] 0 0
Sachsen
Country [9] 0 0
Italy
State/province [9] 0 0
Campania
Country [10] 0 0
Italy
State/province [10] 0 0
Liguria
Country [11] 0 0
Italy
State/province [11] 0 0
Marche
Country [12] 0 0
Spain
State/province [12] 0 0
Cantabria
Country [13] 0 0
Spain
State/province [13] 0 0
Barcelona
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Glasgow
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a study to evaluate the efficacy (effectiveness) and the safety of regorafenib when
given in combination with chemotherapy mFOLFOX6 as first line therapy in patients with
metastatic colorectal cancer (CRC). mFOLFOX6 is an approved chemotherapy. Regorafenib is an
oral (i.e. taken by mouth) multi-targeted kinase inhibitor. A kinase inhibitor targets
certain key proteins that are essential for the survival of the cancer cell. By specifically
targeting these proteins, regorafenib may stop cancer growth. The growth of the tumor may be
decreased by preventing these specific proteins from functioning.

The primary endpoint (the most meaningful result to be tracked) of this study is based on the
rate of response, i.e. the disease getting smaller. The aim is to show that the therapy of
colorectal cancer with mFOLFOX6 in combination with regorafenib improves the response rate
observed for the standard therapy only.
Trial website
https://clinicaltrials.gov/show/NCT01289821
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications