Pulsatile High-dose Sunitinib Versus TAS-102 in Patients With Metastatic Colorectal Carcinoma (mCRC)

NCT03909724 | Unknown Phase 2 DMC

• 1 other identifier: NL60716.029.18.
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare progression free survival rates of metastasized colorectal cancer patients refractory or intolerant to systemic therapy with fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy and anti-EGFR therapy (for tumours with wild-type KRAS)); randomized for treatment with TAS-102 (standard-arm) or High Dose Intermittent Sunitinib (700 mg once every 2 weeks). The investigators hypothesis is that treatment with the experimental arm (sunitinib) will provide an improvement in progression free in this patient group.

Conditions

Colorectal Cancer; Metastasis

Keywords

colorectal cancer; TAS-102; Sunitinib

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Counting from the date of study inclusion (date of randomization) to the date of progressive disease (or death)

  Counting from the date of study inclusion (date of randomization) to the date of progressive disease or death (1 year follow-up). Analysis after inclusion of 33% of patients (N=20)

Secondary Outcomes (4)

• Overall Survival (OS)

  From the date of randomization up to the date of death, assessed up to 12 months. If study medication is discontinued for any reason, survival follow-up takes place every 12 weeks, also assessed up to 12 months

• Adverse events (AEs)

  At the end of the study, after 12 months, the number of participants with adverse events that are related to both treatments will be assessed and compared

• Health-related quality of life (HRQoL): European Organisation for Research and Treatment of Cancer Quality of Life questionnaires (EORTC QoL)

  via EORTC questionnaires, which will be filled in every 8-9 weeks (from date of randomization until the date of first documented progression or date of death, assessed up to 3 years). The questionnaires of both treatments will be assessed and compared

• Liquid biopsies

  The specific time points during study treatment are: (1) at baseline; (2) every 2 weeks during treatment (until progression of disease), assessed up to 12 months .

Study Arms (2)

TAS-102 (Lonsurf)

ACTIVE COMPARATOR

35 mg per square meter, twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest period.

Drug: TAS 102

High Dose Intermittent Sunitinib

EXPERIMENTAL

700 mg once every 2 weeks.

Drug: Sunitinib Malate

Interventions

Sunitinib Malate DRUG

After study inclusion, patients will be randomized (1:1) via a centralized randomization system to receive either oral sunitinib (700 mg once every 2 weeks) or TAS-102 (35 mg per square meter, twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest period). Patients will receive treatment until disease progression or discontinuation due to unacceptable toxic effects, withdrawal of consent, or other reason.

Also known as: Sutent

High Dose Intermittent Sunitinib

TAS 102 DRUG

After study inclusion, patients will be randomized (1:1) via a centralized randomization system to receive either oral sunitinib (700 mg once every 2 weeks) or TAS-102 (35 mg per square meter, twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest period). Patients will receive treatment until disease progression or discontinuation due to unacceptable toxic effects, withdrawal of consent, or other reason.

Also known as: Lonsurf

TAS-102 (Lonsurf)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed (by the patient or legally acceptable representative) and dated Informed Consent Form (ICF).
• Histological or cytological confirmed, documentation of incurable locally advanced or metastatic, colorectal adenocarcinoma, not amenable for potentially curative treatment (i.e. inoperable).
• 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)).
• Evaluable disease by RECIST version 1.1 criteria (see appendix III).
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 3.
• Normal 12-lead ECG (clinically insignificant abnormalities permitted).
• No signs of clinical thyroid abnormalities (suppletion or blocking drugs permitted).
• Adequate bone marrow function
• Adequate liver function
• Albumin higher than 25 g per L
• Serum creatinine ≤1.5 x ULN
• 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.

You may not qualify if:

• Previous treatment with sunitinib and/or TAS-102 for mCRC.
• 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.
• 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).
• 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.
• Instable seizure disorders requiring anticonvulsant therapy.
• Major surgery, other than diagnostic surgery, within 4 weeks prior to day 1, without complete recovery.
• Uncontrolled bleeding disorders, and/or active bleeding.
• Known active bacterial, viral, fungal, mycobacterial, or other infection. (including HIV and atypical mycobacterial disease, but excluding fungal infection of the nail beds.)
• Known hypersensitivity to sunitinib, TAS-102, or to its excipients.
• Presence of any significant psychiatric disorder(s) that would interfere with the patient's compliance.
• 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.
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
• Untreated or active central nervous system (CNS) metastases.
• Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline of \> 3 loose stools daily despite medication.
• Unresolved bowel obstruction

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

Radboud UMC

Nijmegen, 6525 GA, Netherlands

RECRUITING

Related Publications (1)

• Janssen JBE, Iyer KK, Gerritse SL, Janssen E, Gootjes EC, Labots M, Buffart TE, Wumkes ML, Douma JAJ, Streppel MM, Buffart LM, Jonker MA, van den Hombergh E, van Erp NP, Medema JP, Tauriello DVF, Poel D, Verheul HMW. SUNRISE-CRC: a randomized phase II study of high-dose intermittent sunitinib versus trifluridine/tipiracil in metastatic colorectal carcinoma. Oncologist. 2025 Oct 1;30(10):oyaf288. doi: 10.1093/oncolo/oyaf288.

  PMID: 40973474 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

Sunitinib; trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Henk Verheul, Prof. M.D.

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sophie Gerritse, M.D

CONTACT

+31 (0)6 21 000 286; sophie.gerritse@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. H.M.W. Verheul

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: April 10, 2019
• Study Start: October 1, 2019
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2022
• Last Updated: November 13, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)