A trial testing TAS-102 therapy versus an alternative high-dose, intermittent scheduling for sunitinib in patients with metastatic colorectal carcinoma.

Phase 1

• Conditions: Advanced colorectal tumors; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000364-15-NL
• Lead Sponsor: VU University Medical Center, Department of Medical

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-09-11
• Last Update Posted: 29 November 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

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 KRAS)).
4: Evaluable disease by RECIST version 1.1 criteria (see appendix III).
6: Age = 18 years.
7: Eastern Cooperative Oncology Group (ECOG) Performance Status of < 3.
8: Normal 12-lead ECG (clinically insignificant abnormalities permitted).
9: No signs of clinical thyroid abnormalities (suppletion or blocking drugs permitted).
10: 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,
11: 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).
12: Albumin higher than 25 g/L
13: Serum creatinine <1.5 x ULN or creatinine clearance ? 50 ml/min/1.73m2 (based on MDRD).
14: 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

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 clinical trial of medicinal product
• Study Design: Not specified