This study has been transitioned to CTIS with ID 2024-519204-27-00 check the CTIS register for the current data. To evaluate the efficacy of trifluridine/tipiracil by determination of the percentage of patients being progression free at 8 weeks on…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage of patients being progression free at 8 weeks on
trifluridine/tipiracil prescribed for ER-positive, HER2-negative advanced
breast cancer patients previously treated with a taxane and capecitabine
Secondary outcome
• Progression-free survival
• Response rate CR/PR at 16 weeks
• Adverse events
• QoL
Background summary
Treatment goals for metastatic breast cancer (MBC) are palliative in nature,
primarily focused on decreasing tumor size, reducing tumor-related complaints
and extending survival with preservation of quality of life. In patients with
ER-positive, HER2-negativeadvanced disease without rapidly progressive visceral
metastases, deprivation of estrogen signaling is first choice. In the case of
endocrine resistance or rapidly progressive disease chemotherapy is required.
Preclinical studies with trifluridine/tipiracil have demonstrated that
colorectal cancer patients that were pretreated with a fluoropyrimidine (among
others) show an overall survival benefit from trifluridine/tipiracil as
compared to placebo. Trifluridine/tipiracil appears to be tolerated well and
does not cause hand-foot syndrome HFS of importance. It may be anticipated that
patients with ER-positive, HER2-negative advanced breast cancer refractory to
capecitabine may have benefit from trifluridine/tipiracil. Therefore, it is
proposed to study the efficacy and the safety of trifluridine/tipiracil in
disease pretreated with a taxane and capecitabine.
Study objective
This study has been transitioned to CTIS with ID 2024-519204-27-00 check the CTIS register for the current data.
To evaluate the efficacy of trifluridine/tipiracil by determination of the
percentage of patients being progression free at 8 weeks on
trifluridine/tipiracil prescribed for ER-positive, HER2-negative advanced
breast cancer patients previously treated with an anthracycline, a taxane and
capecitabine
Study design
This is a multicenter phase 2 study evaluating the efficacy and safety of
trifluridine/tipiracil in women with metastatic or locally advanced breast
cancer not amenable to curative treatment by surgery or radiotherapy. This
study will be conducted under the sponsorship of BOOG, Amsterdam, NL.
Study medication should be started within 3 days after completion of screening
and continue until a
study treatment discontinuation criterion is met.
Trifluridine/tipiracil will be administered orally BID on days 1 through 5,
with the first dose administered in the morning of day 1 of each cycle and the
last dose administered in the evening of day 5, followed by a recovery period
from day 6 through day 7. Trifluridine/tipiracil will be administered orally
BID on days 8 through 12, with the first dose administered in the morning of
day 8 of each cycle and the last dose administered in the evening of day 12,
followed by a recovery period from day 13 through day 28. Each cycle will be 28
days.
Patients will be evaluated for PFS and ORR. Tumor assessments will be performed
throughout the study based on Response Evaluation Criteria in Solid Tumors
version 1.1 (RECIST 1.1) as described in Section 9.0. Computed tomography (CT)
scans will be performed in week 8 and then 16 weeks. CT scan should be repeated
at 20 weeks to confirm CR/PR at 16 weeks. Safety will be assessed by AEs and
laboratory evaluations according to the Common Terminology Criteria for Adverse
Events (CTC-AE version 4.03).
Intervention
trifluridine/tipiracil 35mg/m2, twice daily, p.o. day 1-2-3-4-5 & 8-9-10-11-12
Repeat every 28 days
Study burden and risks
Physical examination before treatment, before cycle 2 and 30 days after
stopping.
Quality of life questionnaires prior to the study and after 8, 16, 24 and 32
weeks
In addition to the standard treatment:
pregnancy test (urine dipstick)
1x ECG
maximum 2 CT scans
maximum 1 bone scan
Like all medications, the medications that patients receive during this study
can have side effects. Most of the side effects disappear once the study drug
is stopped. Sometimes the side effects can be serious. They can remain present
for a long time or possibly be fatal. Furthermore, some measurements can cause
inconveniences or complications. Side effects, discomforts or complications can
also occur that are still unknown.
The use of this medications may have a beneficial effect on the disease.
Previous research in patients with colon cancer shows that, despite earlier use
of 5-FU / capecitabine, they may have a survival advantage of the research drug
trifluridine / tipiracil (TAS102, LONSURF®). It is expected that this
beneficial effect can also be seen in metastatic ER positive, Her-2 negative
breast cancer.
Godebaldkwartier 363
Utrecht 3511DT
NL
Godebaldkwartier 363
Utrecht 3511DT
NL
Listed location countries
Age
Inclusion criteria
1. Adult women(>= 18 years of age) with proven diagnosis of metastatic or
locally advanced breast cancer not amenable to curative treatment by surgery or
radiotherapy
2. Documented ER positive (10%) / PR positive (10%) and HER2 negative
metastatic breast cancer
3. Progressive disease based on imaging
4. Women previously treated with capecitabine (in metastatic setting), and a
maximum of two other lines of chemotherapy including a
taxane either in the (neo)adjuvant or metastatic setting.
5. Evaluable disease as defined per RECIST v.1.1 (see Appendix A). Tumor lesions
previously irradiated or subjected to other locoregional therapy will
only be deemed
measurable if disease progression at the treated site after completion
of therapy is
clearly documented.
6. Eastern Cooperative Oncology Group (ECOG) performance status<= 1
7. Life expectancy of >= 12 weeks
8. Willing and able to comply with scheduled visits and study procedures
9. Adequate organ, bone marrow and coagulation function as shown by:
• Absolute neutrophil count (ANC) >= 1.5 ×109/L
• Platelets >= 75 ×109/L
• Hemoglobin (Hgb) >= 5.6 mmol/L
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=
2.5 ULN (or <= 5 if hepatic metastases are present)
• Total serum bilirubin <= 1.5 × ULN (<= 3 × ULN for patients known to have
Gilbert Syndrome)
• Creatinine clearance >=60 ml/min
10. Written informed consent obtained before any screening procedure and
according to local guidelines.
11. Resolution of all acute toxic effects of prior anti-cancer therapy or
surgical procedures to NCI CTCAE version 4.0 Grade <=1, except
alopecia or other toxicities not considered a safety risk for the
patient at investigator's discretion.
Exclusion criteria
1. HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or
in situ hybridization positive) and ER-negative patients are not eligible
2. No more than two lines of chemotherapy for advanced disease
3. Remaining of side-effects from previous chemotherapy > grade 1 (except for
alopecia)
4. Radiotherapy within four weeks prior to enrollment is not allowed except in
case of localized radiotherapy for analgesic purpose or for lytic lesions at
risk of fracture which can then be completed within two weeks prior to
enrollment. Patients must have recovered from radiotherapy toxicities prior to
enrollment.
5. 30% or more marrow-bearing bone being irradiated. Other primary tumors
within the last 5 years before study entry are not allowed, except for
adequately controlled basal cell carcinoma of the skin, or carcinoma in situ of
the cervix.
6. Previous or current CNS metastases, carcinomatous meningitis, are not
allowed. A CT or MRI of the brain must be performed within 4 weeks prior to
registration if the presence of metastases at this site is suspected.
7. Evidence of clinically significant cardiovascular or pulmonary disease or
any other disease, metabolic or psychological dysfunction, physical examination
finding, or clinical laboratory finding giving reasonable suspicion of a
disease or condition that contraindicates the use of an investigational drug,
or that may affect patient compliance with study routines, or places the
patient at high risk from treatment related complications. (e.g lactose
intolerance)
8. Previously received trifluridine/tipiracil
9. Since trifluridine/tipiracil contains lactose, patients with rare hereditary
problems of galactose intolerance, the Lapp lactase deficiency or
glucose-galactose malabsorption should not take this medicine (see section 4.4
of the SmPC). (APPENDIX B)
10. Diagnosis of any other malignancy prior to registration, except those that
are not believed to influence the patient*s prognosis and do not require any
further treatment.
11. Other severe acute or chronic medical or psychiatric condition or
laboratory abnormality that may increase the risk associated with study
participation or investigational product administration or may interfere with
the interpretation of study results and, in the judgment of the investigator,
would make the patient inappropriate for entry into this study.
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 |
|---|---|
| EU-CTR | CTIS2024-519204-27-00 |
| EudraCT | EUCTR2019-001706-15-NL |
| ClinicalTrials.gov | NCT04489173 |
| CCMO | NL69646.078.19 |