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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
Sponsor:
Collaborators:
Clinical Trial Center North (CTC North GmbH & Co. KG)
Servier Affaires Médicales
Information provided by (Responsible Party):
Universitätsklinikum Hamburg-Eppendorf

Study Description
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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

Condition or disease Intervention/treatment Phase
Locally Advanced Rectal Cancer Combination Product: Trifluridine/tipiracil chemoradiation Combination Product: Capecitabine based chemoradiation Phase 1 Phase 2

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.

Study Design
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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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Trifluridine/tipiracil based radiotherapy
Trifluridine/tipiracil based chemoradiotherapy (CRT)
 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


Outcome Measures
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Primary Outcome Measures :
  1. Maximum tolerated dose (MTD)/Phase 1 part [ Time Frame: 8 weeks ]
    Toxicity

  2. Rate of pathological complete remissions (pCR)/Phase 2 part [ Time Frame: 3 months ]
    Pathohistological response


Secondary Outcome Measures :
  1. Disease free survival (DFS) [ Time Frame: 4 years ]
    recurrence and survival

  2. Overall survival (OS) [ Time Frame: 4 years ]
    Survival

  3. Loco-regional failure [ Time Frame: 4 years ]
    Loco-regional recurrence

  4. Histopathological R0 resection rate [ Time Frame: 3 months ]
    Pathohistological response

  5. Tumour regression grades [ Time Frame: 3 months ]
    Pathohistological response

  6. Pathological down-staging (ypT0-2N0) rate [ Time Frame: 3 months ]
    Pathohistological response

  7. Neoadjuvant rectal score (NAR) [ Time Frame: 3 months ]
    Clinical stage and Pathohistological response (<8 low, 8-16 intermediate, >16 high risk)

  8. Adverse event rate [ Time Frame: 3 months ]
    Rate of adverse events according to NCI CTC AE v5

  9. Rate of perioperative complications [ Time Frame: 3 months ]
    Perioperative complications


Eligibility Criteria
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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
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Alexander Stein +49(0)403603522 ext 0 stein@hope-hamburg.de
Contact: Marianne Sinn +49(0)407410 ext 0 ma.sinn@uke.de

Locations
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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   
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Clinical Trial Center North (CTC North GmbH & Co. KG)
Servier Affaires Médicales
Investigators
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Principal Investigator: Alexander Stein University Cancer Center Hamburg
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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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

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Universitätsklinikum Hamburg-Eppendorf:
trifluridine tipiracil chemoradiation
locally advanced rectal cancer
neoadjuvant
adenocarcinoma of the rectum
Additional relevant MeSH terms:
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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