Evaluating Trifluridine/Tipiracil Based Chemoradiation in Locally Advanced Rectal Cancer - The Phase I/II TARC Trial

Locally Advanced Rectal Cancer Clinical Trial

Official title:

Evaluating Trifluridine/Tipiracil Based Chemoradiation in Locally Advanced Rectal Cancer - The Phase I/II TARC Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04177602
• Other study ID #: TARC-01
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 4, 2019
• Est. completion date: September 2, 2022

Study information

• Verified date: February 2023
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Seamless phase I/II trial with phase I part for determination of maximum tolerated dose (MTD) of Trifluridine/tipiracil, followed by a randomized phase II trial (randomization ratio 2:1) with an experimental arm with Trifluridine/tipiracil based chemoradiotherapy (CRT) and a standard - calibration arm (internal control) with capecitabine CRT flanked by translational research in patients with locally advanced rectal cancer

Description:

This is a multicenter randomized seamless phase I/II trial with a phase I for determination of maximum tolerated dose (MTD) of Trifluridine/tipiracil, followed by a randomized phase II trial (randomization ratio 2:1) with an experimental arm with Trifluridine/tipiracil in combination with standard radiotherapy and a standard - calibration arm (internal control) with capecitabine CRT flanked by translational research, designed to assess the clinical performance and efficacy of Trifluridine/tipiracil compared to current standard capecitabine chemoradiation in patients with locally advanced rectal cancer. The primary clinical objective in phase I is to determine the dosage and feasibility of Trifluridine/tipiracil based chemoradiation and in phase II whether Trifluridine/tipiracil with preoperative chemoradiation improves pathological complete remissions in patients with locally advanced rectal cancer. The secondary objectives are to evaluate Trifluridine/tipiracil chemoradiation with respect to disease free survival, overall survival, local regional failure, pathological down-staging (ypT0-2N0) rate, tumour regression grade, histopathological R0 resection rate, neoadjuvant rectal score (NAR), and perioperative complication rate. Safety and toxicity, according to NCI CTC AE v5, quality of life and feasibility of the regimen are further secondary objectives that are to be evaluated.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: September 2, 2022
• Est. primary completion date: September 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Male or female patients with histologically proven adenocarcinoma of the rectum (tumour = 12 cm from the anal verge)

2. Indication for neoadjuvant chemoradiation: clinical tumour stage T3/4 or any node-positive disease (clinical stage according the TNM classification system, based on MRI).

3. No evidence of metastatic disease (as evidenced by negative CT-scan of the chest and abdomen).

4. The disease must be considered either resectable at the time of entry or expected to become resectable after preoperative chemoradiation.

5. Age = 18 years

6. WHO/ECOG Performance Status = 2

7. No prior cytotoxic chemotherapy or radiotherapy for rectal cancer.

8. No prior radiotherapy to the pelvis, for any reason.

9. Presence of adequate contraception in fertile patients. Adequate methods of contraception are: intra-uterine device, hormonal contraception, condom use with spermicide. Pregnant or breastfeeding women are excluded from participation.

10. Adequate bone marrow, hepatic and renal function: Haemoglobin =9.0 g/dL (transfusions allowed to achieve or maintain levels), absolute neutrophil count = 1.5 x 109/L, platelet count = 100 x 109/L, ALAT, ASAT = 2.5 x ULN, Alkaline phosphatase = 2.5 x ULN, Total bilirubin =1.5 x ULN, Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault).

11. Ability to swallow tablets.

12. Written informed consent and patient's agreement to comply with the study protocol.

Exclusion Criteria:

1. Previous (within the last 3 years) or concurrent malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the skin.

2. Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction within the last 12 months.

3. Known allergy or any other adverse reaction to any of the study drugs or to any related compound.

4. Known significant impairment of intestinal resorption (e.g. chronic diarrhea, inflammatory bowel disease).

5. Pre-existing condition which would deter chemoradiotherapy or radiotherapy, i.e. fistulas, severe ulcerative colitis (particularly patients currently taking sulphasalazine), Crohn's disease, prior adhesions.

Related Conditions & MeSH terms

• Locally Advanced Rectal Cancer
• Rectal Neoplasms

Intervention

Combination Product:
• Trifluridine/tipiracil chemoradiation
Trifluridine/tipiracil based chemoradiation
• Capecitabine based chemoradiation
Capecitabine based chemoradiation

Locations

Country	Name	City	State
Germany	Malteser Krankenhaus St. Franziskus Hospital	Flensburg	Schleswig-Holstein
Germany	University Medical Center Halle	Halle/Saale
Germany	Hämatologisch- Onkologische Praxis Altona (HOPA)	Hamburg
Germany	Hämatologisch- Onkologische Praxis Eppendorf (HOPE)	Hamburg
Germany	II. Medizinische Klinik und Poliklinik Hubertus Wald Tumorzentrum - UCCH	Hamburg
Germany	Überörtliche Gemeinschaftspraxis für Innere Medizin Schwerpunkt Hämatologie, Onkologie und Palliativmedizin Dres. Verpoort, Wierecky & Zeller	Hamburg
Germany	Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt, Kirso, Weber	Luebeck	Schleswig-Holstein
Germany	Klinik Dr. Hancken / MVZ Onkologie	Stade	Schleswig-Holstein

Sponsors (3)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf	Clinical Trial Center North (CTC North GmbH & Co. KG), Servier Affaires Médicales

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD)/Phase 1 part	Toxicity	8 weeks
Primary	Rate of pathological complete remissions (pCR)/Phase 2 part	Pathohistological response	3 months
Secondary	Disease free survival (DFS)	recurrence and survival	4 years
Secondary	Overall survival (OS)	Survival	4 years
Secondary	Loco-regional failure	Loco-regional recurrence	4 years
Secondary	Histopathological R0 resection rate	Pathohistological response	3 months
Secondary	Tumour regression grades	Pathohistological response	3 months
Secondary	Pathological down-staging (ypT0-2N0) rate	Pathohistological response	3 months
Secondary	Neoadjuvant rectal score (NAR)	Clinical stage and Pathohistological response (<8 low, 8-16 intermediate, >16 high risk)	3 months
Secondary	Adverse event rate	Rate of adverse events according to NCI CTC AE v5	3 months
Secondary	Rate of perioperative complications	Perioperative complications	3 months