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Locally Advanced Rectal CancerPhase 1/2NCT04177602

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

A Phase 1/2 study testing Trifluridine/tipiracil chemoradiation and Capecitabine based chemoradiation in people with Locally Advanced Rectal Cancer, run by Universitätsklinikum Hamburg-Eppendorf at 8 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Locally Advanced Rectal Cancer
What is being tested?
Trifluridine/tipiracil chemoradiation and Capecitabine based chemoradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
8 sitesGermany
Study dates
4 Nov 2019to 2 Sep 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Germany8 sites

  • Malteser Krankenhaus St. Franziskus Hospital

    Flensburg, Schleswig-Holstein, 24939

  • University Medical Center Halle

    Halle

  • Hämatologisch- Onkologische Praxis Eppendorf (HOPE)

    Hamburg, 20249

  • II. Medizinische Klinik und Poliklinik Hubertus Wald Tumorzentrum - UCCH

    Hamburg, 20251

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

    Hamburg, 20259

  • Hämatologisch- Onkologische Praxis Altona (HOPA)

    Hamburg, 22767

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

    Lübeck, Schleswig-Holstein, 23562

  • Klinik Dr. Hancken / MVZ Onkologie

    Stade, Schleswig-Holstein, 21680

Other trials in Germany

About this study

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

Read the detailed 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.

Being tested
Trifluridine/tipiracil chemoradiation, Capecitabine based chemoradiation
Keywords
trifluridine tipiracil chemoradiation, locally advanced rectal cancer, neoadjuvant, adenocarcinoma of the rectum
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trifluridine/tipiracil chemoradiationCombination product

    Trifluridine/tipiracil based chemoradiation

  • Capecitabine based chemoradiationCombination product

    Capecitabine based chemoradiation

Study groups in NCT04177602
Study groupRoleWhat they receive
Trifluridine/tipiracil based radiotherapyExperimentalTrifluridine/tipiracil based chemoradiotherapy (CRT)
Receives: Combination Product: Trifluridine/tipiracil chemoradiation
standard calibration arm (internal control)Active comparatorcapecitabine based chemoradiotherapy
Receives: Combination Product: Capecitabine based chemoradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD)/Phase 1 part

    Toxicity

    Measured: 8 weeks

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

    Pathohistological response

    Measured: 3 months

Secondary outcomes (9)

  1. Disease free survival (DFS)

    recurrence and survival

    Measured: 4 years

  2. Overall survival (OS)

    Survival

    Measured: 4 years

  3. Loco-regional failure

    Loco-regional recurrence

    Measured: 4 years

  4. Histopathological R0 resection rate

    Pathohistological response

    Measured: 3 months

  5. Tumour regression grades

    Pathohistological response

    Measured: 3 months

  6. Pathological down-staging (ypT0-2N0) rate

    Pathohistological response

    Measured: 3 months

  7. Neoadjuvant rectal score (NAR)

    Clinical stage and Pathohistological response (<8 low, 8-16 intermediate, >16 high risk)

    Measured: 3 months

  8. Adverse event rate

    Rate of adverse events according to NCI CTC AE v5

    Measured: 3 months

  9. Rate of perioperative complications

    Perioperative complications

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Nov 2019
  2. Study start4 Nov 2019
  3. Primary completion2 Sep 2022
  4. Study completion2 Sep 2022

Why it stopped: Due to the amended therapy strategies for rectal cancer recently, it was decided not to transfer the study to the phase II part, as superiority over standard chemoradiation and transfer to a new therapy standard are increasingly unlikely.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
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 blind
Who is masked
Participant
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04177602
Sponsor's protocol ID
TARC-01
Status last verified
Feb 2023
First submitted
20 Nov 2019
Last updated
22 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 39003182

  • 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.

    PubMed 32891715

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Trifluridine/tipiracil chemoradiation and Capecitabine based chemoradiation in people with Locally Advanced Rectal Cancer, run by Universitätsklinikum Hamburg-Eppendorf at 8 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Due to the amended therapy strategies for rectal cancer recently, it was decided not to transfer the study to the phase II part, as superiority over standard chemoradiation and transfer to a new therapy standard are increasingly unlikely.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD)/Phase 1 part (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04177602, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2023.

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