A randomized phase II study of pulsatile high-dose sunitinib versus TAS-102 in patients with metastatic colorectal carcinoma (mCRC).
- Conditions
- metastatic colorectal carcinoma1001799010017991
- Registration Number
- NL-OMON53126
- Lead Sponsor
- Radboud Universitair Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 70
To be eligible for this trial, patients will need to meet all of the following
inclusion criteria. Screening must be performed no more than 14 days prior to
the first study drug dose., 1: Signed (by the patient or legally acceptable
representative) and dated Informed Consent Form (ICF). , 2: Histological or
cytological confirmed, documentation of incurable locally advanced or
metastatic, colorectal adenocarcinoma, not amenable for potentially curative
treatment (i.e. inoperable).
3: Indication for treatment with TAS-102; progressive on (or intolerant to)
therapy including fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy
and anti-EGFR therapy (for tumours with wild-type RAS, BRAF and a left sided
tumour)). , 4: Evaluable disease by RECIST version 1.1 criteria (see appendix
III)., 5: Age >= 18 years. , 6: Eastern Cooperative Oncology Group (ECOG)
Performance Status of 0-2., 7: Normal 12-lead ECG (clinically insignificant
abnormalities permitted)., 8: No signs of clinical thyroid abnormalities
(suppletion or blocking drugs permitted)., 9: Adequate bone marrow function;
hemoglobin > 5.6 mmol/l, absolute neutrophil count (ANC) > 1,5 x 10*9/l,
Platelet count *> 100 x 10*9/l, , 10: Adequate liver function; total bilirubin<
1.5 times the upper limit of normal (ULN), ALT and AST < 2.5 x ULN (In case of
liver metastases: <; 5 x ULN)., 11: Albumin higher than 25 g/L, 12: Serum
creatinine <;1.5 x ULN or creatinine clearance * 50 ml/min/1.73m2 (based on
MDRD)., 13: Pregnant or breast-feeding subjects: Women of childbearing
potential must have a negative pregnancy test performed within 7 days of the
start of treatment. For fertile men or women of childbearing potential:
documented willingness to use a highly effective means of contraception (e.g.,
hormonal methods [implants, injectables, or combined oral contraceptives],
intrauterine devices, sexual abstinence, or vasectomized or surgically
sterilized partner). Contraception is necessary for at least 6 months after
receiving the study medication.
The following criteria exclude the patient from enrollment in this trial, 1:
Previous treatment with sunitinib and/or TAS-102 for mCRC., 2: Evidence of
significant uncontrolled concomitant disease, such as cardiovascular disease
(including stroke, New York Heart Association Class III or IV cardiac disease
or myocardial infarction within 6 months prior to screening, unstable
arrhythmia, clinically significant valvular heart disease and unstable angina);
pulmonary disease (including obstructive pulmonary disease > GOLD 2 and
inadequately treated symptomatic bronchospasm), and uncontrolled central
nervous system, renal, hepatic, endocrine, or gastrointestinal disorders; or a
serious non-healing wound or fracture., 3: Extensive prior radiotherapy in the
rectum, pelvis or in more than 3 vertebrae in the spine (less than 3 vertebrae
are considered a small radiation field and eligibility will be decided on an
individual basis from the PI)., 4: Poorly controlled hypertension despite
adequate blood pressure medication. Blood pressure must be <=160/95 mmHg at the
time of screening on a stable antihypertensive regimen. Blood pressure must be
stable on at least 2 separate measurements., 5: Instable seizure disorders
requiring anticonvulsant therapy., 6: Major surgery, other than diagnostic
surgery, within 4 weeks prior to day 1, without complete recovery., 7:
Uncontrolled bleeding disorders, and/or active bleeding., 8: Known active
bacterial, viral, fungal, mycobacterial, or other infection. (including HIV and
atypical mycobacterial disease, but excluding fungal infection of the nail
beds.), 9: Known hypersensitivity to sunitinib, TAS-102, or to its excipients.,
10: Presence of any significant psychiatric disorder(s) that would interfere
with the patient*s compliance., 11: Chemotherapy, radiotherapy, or other
anti-cancer therapy within the previous 4 weeks; no nitrosoureas or mitomycin C
within the previous 6 weeks; no investigational agents within the previous 4
weeks., 12: Clinically significant history of liver disease, including viral or
other hepatitis, current alcohol abuse, or cirrhosis., 13: Untreated or active
central nervous system (CNS) metastases., 14: Predisposing colonic or small
bowel disorders in which the symptoms are uncontrolled as indicated by baseline
of >3 loose stools daily despite medication., 15: Unresolved bowel obstruction,
16: Any evidence of a disease or condition that might affect compliance with
the protocol or interpretation of the study results or render the patient at
high risk from treatment complications.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective is progression-free survival (PFS); defined as the time<br /><br>from randomization to the date of the first documented tumor progression;<br /><br>determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1<br /><br>criteria or death due to any cause. We hypothesize that sunitinib will result<br /><br>in a clinically relevant increase in PFS (from 2 months with TAS-102 arm to 5<br /><br>months with).</p><br>
- Secondary Outcome Measures
Name Time Method