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

NCT04177602 | Terminated Phase 1 DMC

• 1 other identifier: TARC-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 8

Brief 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

Conditions

Locally Advanced Rectal Cancer

Keywords

trifluridine tipiracil chemoradiation; locally advanced rectal cancer; neoadjuvant; adenocarcinoma of the rectum

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD)/Phase 1 part

  Toxicity

  8 weeks

• Rate of pathological complete remissions (pCR)/Phase 2 part

  Pathohistological response

  3 months

Secondary Outcomes (9)

• Disease free survival (DFS)

  4 years

• Overall survival (OS)

  4 years

• Loco-regional failure

  4 years

• Histopathological R0 resection rate

  3 months

• Tumour regression grades

  3 months

Study Arms (2)

Trifluridine/tipiracil based radiotherapy

EXPERIMENTAL

Trifluridine/tipiracil based chemoradiotherapy (CRT)

Combination Product: Trifluridine/tipiracil chemoradiation

standard calibration arm (internal control)

ACTIVE COMPARATOR

capecitabine based chemoradiotherapy

Combination Product: Capecitabine based chemoradiation

Interventions

Trifluridine/tipiracil chemoradiation COMBINATION_PRODUCT

Trifluridine/tipiracil based chemoradiation

Trifluridine/tipiracil based radiotherapy

Capecitabine based chemoradiation COMBINATION_PRODUCT

Capecitabine based chemoradiation

standard calibration arm (internal control)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead
• Clinical Trial Center North (CTC North GmbH & Co. KG): collaborator
• Servier Affaires Médicales: collaborator

Study Sites (8)

Malteser Krankenhaus St. Franziskus Hospital

Flensburg, Schleswig-Holstein, 24939, Germany

Location

Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt, Kirso, Weber

Lübeck, Schleswig-Holstein, 23562, Germany

Location

Klinik Dr. Hancken / MVZ Onkologie

Stade, Schleswig-Holstein, 21680, Germany

Location

University Medical Center Halle

Halle, Germany

Location

Hämatologisch- Onkologische Praxis Eppendorf (HOPE)

Hamburg, 20249, Germany

Location

II. Medizinische Klinik und Poliklinik Hubertus Wald Tumorzentrum - UCCH

Hamburg, 20251, Germany

Location

Überörtliche Gemeinschaftspraxis für Innere Medizin Schwerpunkt Hämatologie, Onkologie und Palliativmedizin Dres. Verpoort, Wierecky & Zeller

Hamburg, 20259, Germany

Location

Hämatologisch- Onkologische Praxis Altona (HOPA)

Hamburg, 22767, Germany

Location

Related Publications (2)

• Thiele B, Stein A, Schultheiss C, Paschold L, Jonas H, Goekkurt E, Russel J, Schuch G, Wierecky J, Sinn M, Tintelnot J, Petersen C, Rothkamm K, Vettorazzi E, Binder M. Trifluridine/Tipiracil Based Chemoradiation in locally Advanced Rectal Cancer: The Phase I/II TARC Trial. Clin Colorectal Cancer. 2025 Mar;24(1):11-17. doi: 10.1016/j.clcc.2024.06.003. Epub 2024 Jun 22.

  PMID: 39003182 DERIVED

• Rothkamm K, Christiansen S, Rieckmann T, Horn M, Frenzel T, Brinker A, Schumacher U, Stein A, Petersen C, Burdak-Rothkamm S. Radiosensitisation and enhanced tumour growth delay of colorectal cancer cells by sustained treatment with trifluridine/tipiracil and X-rays. Cancer Lett. 2020 Nov 28;493:179-188. doi: 10.1016/j.canlet.2020.08.038. Epub 2020 Sep 4.

  PMID: 32891715 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Trifluridine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Alexander Stein

  University Cancer Center Hamburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: November 26, 2019
• Study Start: November 4, 2019
• Primary Completion: September 2, 2022
• Study Completion: September 2, 2022
• Last Updated: February 22, 2023

Record last verified: 2023-02

Locations

DE (8)