A Phase 1/2 Study Exploring the Safety and Activity of Trifluridine/Tipiracil in Combination with Capecitabine and Bevacizumab in Metastatic Colorectal Cancer Patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione GONO G.I.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Sep 2024 → ongoing

Decision date (initial)

2024-09-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Servier · Servier

External identifiers

EU CT number

2024-513271-41-00

EudraCT number

2020-000923-37

ClinicalTrials.gov

NCT04564898

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the activity of the combination (trifluridine/tipiracil plus capecitabine plus bevacizumab) in previously untreated mCRC patients deemed unfit for intensive chemotherapy in terms of Objective Response Rate (ORR) per RECIST v1.1.

Secondary objectives 3

1. -To evaluate the safety of the combination (trifluridine/tipiracil plus capecitabine plus bevacizumab).
2. -To evaluate the efficacy of the combination (trifluridine/tipiracil plus capecitabine plus bevacizumab) in terms of Progression Free Survival (PFS) and Overall Survival (OS).
3. -To assess the quality of life as measured by PROs questionnaires (EORTC QLQ-C30 EORTC, QLQ-CR29 and EuroQol EQ-5D).

Conditions and MedDRA coding

colorectal metastatic cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Written informed consent to study procedures.
2. Histologically proven diagnosis of colorectal cancer.
3. Metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
4. At least one measurable lesion according to RECIST1.1.
5. Age = 18 years.
6. ECOG PS = 1
7. Life expectancy of at least 12 weeks.
8. Availability of archival tumour tissue (primary tumour and metastases or at least one of the two) for biomarker analysis
9. Previously not eligible for a chemotherapy doublet or triplet (oxaliplatin and/or irinotecan-based combination)
10. Neutrophils =1.5 x 109/L, Platelets =100 x 109/L, Hemoglobin = 9 g/dl
11. Total bilirubin =1.5 fold the upper-normal limits (UNL), AST (SGOT) and/or ALT (SGPT) = 2.5 x UNL (or <5 x UNL in the case of liver metastases), alkaline phosphatase = 2.5 x UNL (or <5 x UNL in case of liver metastases)
12. Creatinine clearance = 50 mL/min or serum creatinine =1.5 x UNL
13. Male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception)
14. Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
15. Subjects and their partners must be willing to avoid pregnancy during the trial and until 6 months after the last trial treatment.
16. Will and ability to comply with the protocol.

Exclusion criteria 18

1. Radiotherapy to any site within 4 weeks before the study.
2. Previous treatment with trifluridine/tipiracil, bevacizumab and capecitabine (previous • treatment with capecitabine was permitted only in the adjuvant setting and if more than 12 months elapsed between the end of adjuvant and first relapse).
3. Untreated brain metastases or spinal cord compression or primary brain tumors.
4. History or evidence upon physical examination of CNS disease unless adequately treated.
5. Clinical signs of malnutrition.
6. Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration.
7. Evidence of bleeding diathesis or coagulopathy
8. Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.
9. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (=6 months), myocardial infarction (=6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia equiring medication.
10. Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment.
11. Any previous venous thromboembolism = NCI CTCAE Grade 4.
12. History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment.
13. Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer).
14. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ.
15. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
16. Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs.
17. Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies.
18. Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective Response Rate (ORR) is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, determined by investigator reported measurements. According to RECIST 1.1 criteria and the non-randomised nature of the study, a confirmation of CR and PR is required.

Secondary endpoints 5

1. Overall Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0)
2. Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 5.0).
3. Progression Free Survival (PFS)
4. Overall Survival (OS)
5. The analysis of PROs endpoints

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione GONO G.I.

Sponsor organisation

Fondazione GONO G.I.

Address

Via Goffredo Mameli 3/1

City

Genoa

Postcode

16122

Country

Italy

Scientific contact point

Organisation

Gruppo Oncologico Del Nord Ovest

Contact name

Chiara Cremolini

Public contact point

Organisation

Gruppo Oncologico Del Nord Ovest

Contact name

Chiara Cremolini

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications