Evaluating Trifluridine/Tipiracil Based Chemoradiation in Locally Advanced Rectal Cancer - The Phase I/II TARC Trial
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ClinicalTrials.gov Identifier: NCT04177602 |
Recruitment Status :
Recruiting
First Posted : November 26, 2019
Last Update Posted : March 19, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Locally Advanced Rectal Cancer | Combination Product: Trifluridine/tipiracil chemoradiation Combination Product: Capecitabine based chemoradiation | Phase 1 Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 122 participants |
Allocation: | Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | 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 |
Masking: | Single (Participant) |
Primary Purpose: | Treatment |
Official Title: | Evaluating Trifluridine/Tipiracil Based Chemoradiation in Locally Advanced Rectal Cancer - The Phase I/II TARC Trial |
Actual Study Start Date : | November 4, 2019 |
Estimated Primary Completion Date : | December 31, 2021 |
Estimated Study Completion Date : | June 1, 2024 |

Arm | Intervention/treatment |
---|---|
Experimental: Trifluridine/tipiracil based radiotherapy
Trifluridine/tipiracil based chemoradiotherapy (CRT)
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Combination Product: Trifluridine/tipiracil chemoradiation
Trifluridine/tipiracil based chemoradiation |
Active Comparator: standard calibration arm (internal control)
capecitabine based chemoradiotherapy
|
Combination Product: Capecitabine based chemoradiation
Capecitabine based chemoradiation |
- Maximum tolerated dose (MTD)/Phase 1 part [ Time Frame: 8 weeks ]Toxicity
- Rate of pathological complete remissions (pCR)/Phase 2 part [ Time Frame: 3 months ]Pathohistological response
- Disease free survival (DFS) [ Time Frame: 4 years ]recurrence and survival
- Overall survival (OS) [ Time Frame: 4 years ]Survival
- Loco-regional failure [ Time Frame: 4 years ]Loco-regional recurrence
- Histopathological R0 resection rate [ Time Frame: 3 months ]Pathohistological response
- Tumour regression grades [ Time Frame: 3 months ]Pathohistological response
- Pathological down-staging (ypT0-2N0) rate [ Time Frame: 3 months ]Pathohistological response
- Neoadjuvant rectal score (NAR) [ Time Frame: 3 months ]Clinical stage and Pathohistological response (<8 low, 8-16 intermediate, >16 high risk)
- Adverse event rate [ Time Frame: 3 months ]Rate of adverse events according to NCI CTC AE v5
- Rate of perioperative complications [ Time Frame: 3 months ]Perioperative complications

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Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male or female patients with histologically proven adenocarcinoma of the rectum (tumour ≤ 12 cm from the anal verge)
- Indication for neoadjuvant chemoradiation: clinical tumour stage T3/4 or any node-positive disease (clinical stage according the TNM classification system, based on MRI).
- No evidence of metastatic disease (as evidenced by negative CT-scan of the chest and abdomen).
- The disease must be considered either resectable at the time of entry or expected to become resectable after preoperative chemoradiation.
- Age ≥ 18 years
- WHO/ECOG Performance Status ≤ 2
- No prior cytotoxic chemotherapy or radiotherapy for rectal cancer.
- No prior radiotherapy to the pelvis, for any reason.
- 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.
- 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).
- Ability to swallow tablets.
- Written informed consent and patient's agreement to comply with the study protocol.
Exclusion Criteria:
- 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.
- 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.
- Known allergy or any other adverse reaction to any of the study drugs or to any related compound.
- Known significant impairment of intestinal resorption (e.g. chronic diarrhea, inflammatory bowel disease).
- 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04177602
Contact: Alexander Stein | +49(0)403603522 ext 0 | stein@hope-hamburg.de | |
Contact: Marianne Sinn | +49(0)407410 ext 0 | ma.sinn@uke.de |
Germany | |
Malteser Krankenhaus St. Franziskus Hospital | Recruiting |
Flensburg, Schleswig-Holstein, Germany, 24939 | |
Contact: Nadezda Basara, Prof +49 461 816 2512 Nadezda.Basara@malteser.org | |
Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt, Kirso, Weber | Recruiting |
Luebeck, Schleswig-Holstein, Germany, 23562 | |
Contact: Jens Kisro, Dr +49 451 70797 226 jens.kisro@t-online.de | |
Klinik Dr. Hancken / MVZ Onkologie | Recruiting |
Stade, Schleswig-Holstein, Germany, 21680 | |
Contact: Johannes Meiler, Dr +49 4141 604 226 Johannes.meiler@hancken.de | |
University Medical Center Halle | Recruiting |
Halle/Saale, Germany | |
Contact: Mascha Binder, Prof mascha.binder@uk-halle.de | |
Contact: Thomas Reese thomas.reese@uk-halle.de | |
Hämatologisch- Onkologische Praxis Eppendorf (HOPE) | Recruiting |
Hamburg, Germany, 20249 | |
Contact: Eray Goekkurt, Dr +49 40 36035 220 goekkurt@onkologie-eppendorf.de | |
II. Medizinische Klinik und Poliklinik Hubertus Wald Tumorzentrum - UCCH | Recruiting |
Hamburg, Germany, 20251 | |
Contact: Marianne Sinn, Dr +49(0)407410 ext 70434 ma.sinn@uke.de | |
Contact: Thomas Mueller +49(0)7410 ext 57725 tho.mueller@uke.de | |
Überörtliche Gemeinschaftspraxis für Innere Medizin Schwerpunkt Hämatologie, Onkologie und Palliativmedizin Dres. Verpoort, Wierecky & Zeller | Recruiting |
Hamburg, Germany, 20259 | |
Contact: Jan Wierecky, Dr +49 40 3571777 0 wierecky@onkologie-hamburg.de | |
Hämatologisch- Onkologische Praxis Altona (HOPA) | Recruiting |
Hamburg, Germany, 22767 | |
Contact: Gunter Schuch, Dr +49 40 380212 60 gunter.schuch@hopa-hamburg.de |
Principal Investigator: | Alexander Stein | University Cancer Center Hamburg |
Responsible Party: | Universitätsklinikum Hamburg-Eppendorf |
ClinicalTrials.gov Identifier: | NCT04177602 |
Other Study ID Numbers: |
TARC-01 |
First Posted: | November 26, 2019 Key Record Dates |
Last Update Posted: | March 19, 2021 |
Last Verified: | March 2021 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
trifluridine tipiracil chemoradiation locally advanced rectal cancer neoadjuvant adenocarcinoma of the rectum |
Rectal Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases |
Rectal Diseases Trifluridine Capecitabine Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents |