This study will evaluate 2 different treatment strategies : a combination of S 95005 and bevacizumab (experimental combination) and a combination of capecitabine and bevacizumab (control arm) as first-line treatment for metastatic colorectal cancer…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression-free survival (PFS) based on Investigator assessment of radiologic
images
Secondary outcome
Overall response rate (ORR)
Duration of response (DR)
Disease control rate (DCR)
Overall survival (OS)
Safety and tolerability
Quality of Life (QoL)
Background summary
S 95005 ( also called TAS-102) is a combination of an antineoplastic
thymidine-based nucleoside analogue (trifluridine [FTD]) and a thymidine
phosphorylase inhibitor (tipiracil hydrochloride [TPI]).
Co-administration of TPI with FTD prevents the rapid degradation of FTD,
resulting in a significant increase in systemic exposure to FTD. Following
uptake into cancer cells, FTD is phosphorylated by thymidine kinase,
further metabolized in cells to a deoxyribonucleic acid (DNA) substrate, and
incorporated directly into DNA, thereby interfering with DNA function to
prevent cell proliferation.
FTD incorporation into DNA is markedly higher than that of other nucleoside
analogues.
FTD also exhibits thymidylate synthase (TS) inhibition. However, results
of in vivo studies show FTD incorporation into DNA to be the primary
mechanism of antitumour activity with oral administration.
This mechanism of action of S 95005 differentiates it from conventional
fluoropyrimidines, which are uracil-based, and for which the primary mode of
action is TS inhibition.
For patients with mCRC who are non-eligible for intensive therapy, recent ESMO
and NCCN guidelines recommend fluorouracil or capecitabine with or without
bevacizumab as first-line treatment.
Based on the demonstrated efficacy and tolerability of S95005 in patients with
previously treated mCRC, including patients refractory to prior
fluoropyrimidine treatment, a Phase 2 study to evaluate the benefit of S95005
plus bevacizumab as first-line treatment of unresectable mCRC is warranted.
The results of a Phase 1/2 study conducted in Japan suggest that the
combination of TAS-102 and bevacizumab is well tolerated in patients with mCRC
Study objective
This study will evaluate 2 different treatment strategies : a combination of S
95005 and bevacizumab (experimental combination) and a combination of
capecitabine and bevacizumab (control arm) as first-line treatment for
metastatic colorectal cancer in patients non-eligible for intensive therapy.
Study design
International, multicentric, randomised(1:1), open-label phase 2 study to
include 150 pats in 2 parallel arms:
* S 95005 + bevacizumab = 4 weeks cycle
* or capecitabine + bevacizumab = 3 weeks cycle
study scheme : screening, inclusion, randomisation, visit on D1 + D15,
afterwards on day of bevacizumab administration and withdrawal visit
Intervention
blood and urine sampling, contrast enhanced CT , QoL questionnaires
Study burden and risks
cfr adverse events of medication and procedures described in patient
information.
Rue Carnot 50
Suresnes 92284
FR
Rue Carnot 50
Suresnes 92284
FR
Listed location countries
Age
Inclusion criteria
- Written informed consent obtained.;- Male or Female participant aged *18 years old.;- Has ECOG performance status of 0, 1 or 2 at the time of the randomisation.;- Has definitive histologically or cytologically confirmed adenocarcinoma of the colon or rectum.;- RAS status must have been determined (mutant or wild).;- Has at least one measurable metastatic lesion.;- No previous anticancer therapy for metastatic colorectal cancer. ;- Previous adjuvant (or neoadjuvant for patients with rectal cancer) chemotherapy is allowed only if if it has been completed more than 6 months before start of study treatment.;- In the judgment of the Investigator, patient is not a candidate for combination chemotherapy with irinotecan or oxaliplatin, or for curative resection of metastatic lesions.;- Is able to take medication orally (i.e., no feeding tube).;- Has adequate organ function.;- Coagulation parameters in normal limit.;- Women of childbearing potential must have been tested negative in a serum pregnancy test. Male and female patients who have the potential to reproduce must agree to use a highly effective method of birth control.;- Is willing and able to comply with scheduled visits and study procedures.
Exclusion criteria
- Foreseeable poor compliance to the study procedures.;- Is a pregnant or lactating female.;- Is inappropriate for entry into this study in the judgment of the Investigator.;- Has certain serious illness or serious medical condition(s) described in the protocol.;- Has had certain other recent treatment e.g. major surgery, field radiation, received investigational agent, within the specified time frames prior to study drug administration.;- Has previously received S 95005 or history of allergic reactions attributed to compounds of similar or biologic composition to S 95005.;- Has contra indications to bevacizumab or capecitabine.;- Has rare hereditary problems of galectose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-004544-18-NL |
| CCMO | NL56482.018.16 |