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

• Sponsor: Universitätsklinikum Hamburg-Eppendorf (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04177602
• Collaborator: Clinical Trial Center North (CTC North GmbH & Co. KG) (Other), Servier Affaires Médicales (Industry)
• Enrollment: 122
• Locations: 8
• Arms: 2
• Anticipated Duration (Months): 54.9
• Patients Per Site: 15.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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

• Study Type: Interventional
• Anticipated 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 researchSeamless 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: Nov 4, 2019
• Anticipated Primary Completion Date: Dec 31, 2021
• Anticipated Study Completion Date: Jun 1, 2024

Arms and Interventions

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

Primary Outcome Measures

1. Maximum tolerated dose (MTD)/Phase 1 part [8 weeks]

   Toxicity

2. Rate of pathological complete remissions (pCR)/Phase 2 part [3 months]

   Pathohistological response

Secondary Outcome Measures

1. Disease free survival (DFS) [4 years]

   recurrence and survival

2. Overall survival (OS) [4 years]

   Survival

3. Loco-regional failure [4 years]

   Loco-regional recurrence

4. Histopathological R0 resection rate [3 months]

   Pathohistological response

5. Tumour regression grades [3 months]

   Pathohistological response

6. Pathological down-staging (ypT0-2N0) rate [3 months]

   Pathohistological response

7. Neoadjuvant rectal score (NAR) [3 months]

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

8. Adverse event rate [3 months]

   Rate of adverse events according to NCI CTC AE v5

9. Rate of perioperative complications [3 months]

   Perioperative complications

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Malteser Krankenhaus St. Franziskus Hospital	Flensburg	Schleswig-Holstein	Germany	24939
2	Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt, Kirso, Weber	Luebeck	Schleswig-Holstein	Germany	23562
3	Klinik Dr. Hancken / MVZ Onkologie	Stade	Schleswig-Holstein	Germany	21680
4	University Medical Center Halle	Halle/Saale		Germany
5	Hämatologisch- Onkologische Praxis Eppendorf (HOPE)	Hamburg		Germany	20249
6	II. Medizinische Klinik und Poliklinik Hubertus Wald Tumorzentrum - UCCH	Hamburg		Germany	20251
7	Überörtliche Gemeinschaftspraxis für Innere Medizin Schwerpunkt Hämatologie, Onkologie und Palliativmedizin Dres. Verpoort, Wierecky & Zeller	Hamburg		Germany	20259
8	Hämatologisch- Onkologische Praxis Altona (HOPA)	Hamburg		Germany	22767

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Alexander Stein, University Cancer Center Hamburg

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Universitätsklinikum Hamburg-Eppendorf
• ClinicalTrials.gov Identifier: NCT04177602
• Other Study ID Numbers: TARC-01
• First Posted: Nov 26, 2019
• Last Update Posted: Mar 19, 2021
• Last Verified: Mar 1, 2021

• 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: Rectal Neoplasms; Trifluridine; Capecitabine

Study Results

No Results Posted as of Mar 19, 2021