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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02365441




Registration number
NCT02365441
Ethics application status
Date submitted
4/11/2014
Date registered
19/02/2015
Date last updated
7/07/2023

Titles & IDs
Public title
A Randomised Trial of Imatinib Alternating With Regorafenib Compared to Imatinib Alone for the First Line Treatment of Advanced Gastrointestinal Stromal Tumour (GIST)
Scientific title
A Randomised Phase II Trial of Imatinib Alternating With Regorafenib Compared to Imatinib Alone for the First Line Treatment of Advanced Gastrointestinal Stromal Tumour (GIST)
Secondary ID [1] 0 0
ACTRN12614000950662
Secondary ID [2] 0 0
AG1013GST
Universal Trial Number (UTN)
Trial acronym
ALT GIST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastrointestinal Stromal Tumour 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach
Cancer 0 0 0 0
Bowel - Small bowel (duodenum and ileum)
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
Treatment: Drugs - imatinib

Active Comparator: Arm A - imatinib 400mg orally daily continuously

Experimental: Arm B - alternating 28-day periods of imatinib 400mg orally daily for 21 to 25 days followed by a washout (drug free) period of 3 to 7 days, then regorafenib 160mg orally daily for 3 weeks followed by a 7 day washout (drug free) period.


Treatment: Drugs: Regorafenib


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

Outcomes
Primary outcome [1] 0 0
Objective tumour response (complete or partial response) as determined by RECIST v1.1
Timepoint [1] 0 0
At or before 9 months from the time from either (i) randomization (if patients have not yet commenced treatment) or (ii) commencement of therapy (if patients are randomized during the first cycle of imatinib)
Secondary outcome [1] 0 0
Progression free survival at 24 months (disease progression or death)
Timepoint [1] 0 0
24 Months
Secondary outcome [2] 0 0
Clinical benefit rate at 24 weeks
Timepoint [2] 0 0
24 weeks
Secondary outcome [3] 0 0
Time to treatment failure
Timepoint [3] 0 0
5 years
Secondary outcome [4] 0 0
Adverse Events
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
Overall survival
Timepoint [5] 0 0
5 years

Eligibility
Key inclusion criteria
- Adults (over 18 yrs) with histologically confirmed GIST. In CD-117-negative cases
DOG-1 must be positive or a KIT/PDGFRA mutation must be present.

- Unresectable, metastatic disease.

- No prior TKI for metastatic disease, with the exception of those patients who have had
up to 21 days of uninterrupted treatment on 400mg daily of imatinib.

- Imatinib therapy given as an adjuvant treatment and completed at least 3 months prior
to entry into this trial is permitted. Patients who have progression of GIST while on
adjuvant therapy are not eligible for this trial.

- ECOG performance status 0-2

- Measurable disease by RECIST version 1.1. (Note: Participants with only peritoneal
disease will be eligible only if they have lesions measurable in two dimensions and
have at least 1 lesion which is = 2 cm in size).

- Adequate bone marrow function (Haemoglobin = 9.0g/dL, platelet count = 100 x 109/L,
and absolute neutrophil count = 1.5 x 109/L).

- Adequate liver function (Serum total bilirubin =1.5 x ULN, INR = 1.5, and ALT, AST,
ALP =2.5 x ULN (= 5 x ULN for participants with liver metastases). Lipase level must
be = 1.5 x ULN.

- Adequate renal function (Creatinine clearance > 50ml/min) based on either the
Cockcroft Gault formula, 24 hour urine or Glomerular Filtration Rate (GFR scan); and
serum creatinine = 1.5 x ULN.

- Tumour tissue available for central review.

- Willing and able to comply with all study requirements, including treatment timing
and/or nature of required assessments.

- Study treatment both planned and able to start within 14 days of randomisation.

- Signed, written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Concurrent GI illness which may prevent absorption of imatinib or regorafenib - please
note that prior gastrectomy or bowel resection does not exclude patients from this
study.

- Use of other investigational drugs within 4 weeks prior to enrolment.

- Known sensitivity to any of the study drugs, study drug classes, or excipients in the
formulation.

- Participants receiving therapeutic doses of warfarin.

- Presence of brain metastases.

- The presence of PDGFR D842V mutation or other mutation known to cause imatinib
resistance.

- Inability to swallow tablets.

- Arterial thrombotic or ischaemic events, such as cerebrovascular accident or pulmonary
embolism within 6 months prior to randomisation; or major venous thrombotic events
requiring use of an anticoagulant such as warfarin within 6 months prior to
randomisation.

- Poorly controlled hypertension (systolic blood pressure > 140 mmHg or diastolic
pressure > 90 mmHg despite optimal medical management).

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to randomisation, or non healing wound, ulcer or fracture.

- Congestive cardiac failure (NYHA = grade 2), unstable angina or new onset angina
within the previous 3 months, or AMI within the previous 6 months. Cardiac arrhythmias
requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).

- Haemorrhage or bleeding event = Grade 3 according to CTCAE v4.0 within 4 weeks prior
to randomisation.

- Ongoing infection of > Grade 2 according to CTCAE v4.0.

- Active hepatitis B or C or HIV, or chronic hepatitis B or C requiring treatment with
antiviral therapy. Testing for these is not mandatory unless clinically indicated.

- Interstitial lung disease with ongoing signs and symptoms.

- Persistent proteinuria of = Grade 3 (>3.5g/24 hours) according to CTCAE v4.0

- Other significant medical or psychiatric condition judged by the investigator to
interfere with protocol requirements.

- Use of biological response modifiers such as granulocyte colony stimulating factor
(G-CSF), within 3 weeks prior to randomisation.

- Patients taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg clarithromycin,
indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole,
ritonavir, saquinovir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg
carbamazepine, phenobarbitol, phenytoin, rifampicin, St John's wort).

- History of another malignancy within 5 years prior to registration. Patients with a
past history of adequately treated 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.

- Pregnancy, lactation, or inadequate contraception. Women must be post menopausal,
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. Women of
childbearing potential and men must agree to use adequate contraception before
entering the trial until at least 8 weeks after the last study drug administration.

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



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
Accrual to date
Final
78
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Canberra Hospital - Canberra
Recruitment hospital [2] 0 0
Calvary Mater Newcastle Hospital - Newcastle
Recruitment hospital [3] 0 0
Prince of Wales Hospital - Sydney
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [5] 0 0
Ashford Cancer Centre Research - Adelaide
Recruitment hospital [6] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [7] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [8] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [9] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [10] 0 0
Sir Charles Gairdner - Perth
Recruitment postcode(s) [1] 0 0
2606 - Canberra
Recruitment postcode(s) [2] 0 0
2310 - Newcastle
Recruitment postcode(s) [3] 0 0
2031 - Sydney
Recruitment postcode(s) [4] 0 0
4120 - Brisbane
Recruitment postcode(s) [5] 0 0
5037 - Adelaide
Recruitment postcode(s) [6] 0 0
5042 - Adelaide
Recruitment postcode(s) [7] 0 0
7001 - Hobart
Recruitment postcode(s) [8] 0 0
3199 - Frankston
Recruitment postcode(s) [9] 0 0
3690 - Wodonga
Recruitment postcode(s) [10] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
Finland
State/province [1] 0 0
Helsinki
Country [2] 0 0
France
State/province [2] 0 0
Bordeaux
Country [3] 0 0
France
State/province [3] 0 0
Dijon
Country [4] 0 0
France
State/province [4] 0 0
Leon
Country [5] 0 0
France
State/province [5] 0 0
Paris
Country [6] 0 0
Netherlands
State/province [6] 0 0
Amsterdam
Country [7] 0 0
Norway
State/province [7] 0 0
Bergen
Country [8] 0 0
Norway
State/province [8] 0 0
Oslo
Country [9] 0 0
Singapore
State/province [9] 0 0
Singapore
Country [10] 0 0
Slovakia
State/province [10] 0 0
NSW
Country [11] 0 0
Spain
State/province [11] 0 0
Barcelona
Country [12] 0 0
Sweden
State/province [12] 0 0
Lund
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Birmingham
Country [14] 0 0
United Kingdom
State/province [14] 0 0
London
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Other
Name
Australasian Gastro-Intestinal Trials Group
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Scandinavian Sarcoma Group
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
An open label randomised trial for adults with histologically confirmed measurable metastatic
GIST who have received no other treatment for metastatic disease. The study aims to determine
if an alternating regimen of imatinib and regorafenib has sufficient activity and safety in
comparison to imatinib alone to warrant further evaluation as a first line treatment for
metastatic GIST.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02365441
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Heikki Joensuu, Professor
Address 0 0
SSG
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02365441