A study of TAS-120 in patients with advanced cancer with genetic abnormalities

Phase 1

• Conditions: Advanced solid tumors; MedDRA version: 20.0 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-004810-16-NL
• Lead Sponsor: Taiho Oncology Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-12-28
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 835

Inclusion Criteria

1. Provide written informed consent.
2. Is = 18 years .
3. Has histologically or cytologically confirmed, locally advanced, metastatic cancer meeting the following criteria:
a. Phase 1 Expansion
I. Patient has failed all standard therapies or standard therapy does not exist or is not tolerated.
ii. Patient is eligible for 1 of the following enrollment groups, based on diagnosis, prior therapy, and FGF/FGFR aberrations as shown:

Group 1 (Enrollment Suspended as of Amendment 7): Patient has
intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR2 gene
fusions.
Group 2: Patient has intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR2 gene fusions, and has not received or received less
than 1 cycle of prior chemotherapy (due to intolerance or patient refusal).
Group 3 (Enrollment Suspended as of Amendment 7): Patient has
intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR2 gene
fusions and has received prior treatment with FGFR inhibitors.
Group 4 (Enrollment suspended as of Amendment 7): Patient has
intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR
abnormalities other than FGFR2 gene fusions.
Group 5: Patient has a primary CNS tumor harboring FGFR gene fusion or
FGFR1 activating mutation and fulfills the criteria (i and ii).
Group 6 (Enrollment Suspended as of Amendment 7): Patient has
advanced urothelial carcinoma harboring FGFR3 fusions or FGFR3
activating mutations.
Group 7: Patient has any tumor type not included in one of the prior
groups, harboring FGFR2 amplification (no minimum number of copies).
Group 8 (Enrollment Suspended as of Amendment 7): Patient has any
tumor type not included in one of the prior groups, harboring FGFR gene
fusions or activating mutations.
b. Phase 2
i. Patient has histologically or cytologically confirmed, locally advanced,
metastatic, unresectable iCCA harboring FGFR2 gene fusions or other
FGFR2 rearrangements based on results from either of the following
a. Testing by Foundation Medicine:
i. As part of study pre-screening; or
ii. Previously tested by Foundation Medicine; in this case, tumor tissue
should be provided to Foundation Medicine if available.
b. Local laboratory testing using next generation sequencing [NGS],
fluorescence in situ hybridization [FISH], or other assays that can
determine FGFR2 gene fusions or other FGFR2 rearrangements on tumor
tissues or from ctDNA; patients enrolled on this basis must have
available tumor tissues from either archival samples or fresh tumor
biopsy submitted to Foundation Medicine for confirmation of FGFR2 gene
fusion or other FGFR2 rearrangements.
ii. Patient has been treated with at least one prior systemic gemcitabine
and platinum-based chemotherapy. Patients with p

Exclusion Criteria

1. History and/or current evidence of clinically significant non-tumor
related alteration of calcium-phosphorus homeostasis.
2. History and/or current evidence of clinically significant ectopic
mineralization/calcification.
3. History and/or current evidence of clinically significant retinal
disorder confirmed by retinal examination.
4. History or current evidence of serious uncontrolled ventricular
arrhythmias
5. Fridericia's corrected QT interval (QTcF) > 470 ms on ECG conducted
during Screening.
6. Treatment with any of the following within the specified time frame
prior to the first dose of TAS-120:
a. Major surgery within the previous 4 weeks (the surgical incision
should be fully healed prior to the first dose of TAS 120).
b. Radiotherapy for extended field within 4 weeks or limited field
radiotherapy within 2 weeks.
c. Patients with locoregional therapy, e.g., transarterial
chemoembolization (TACE), selective internal radiotherapy (SIRT) or
ablation within 4 weeks.
d. Any noninvestigational anticancer therapy within 3 weeks or have
not recovered from side effects of such therapy prior to TAS 120
administration (mitomycin within prior 5 weeks).
• Targeted therapy or immunotherapy within 3 weeks or within 5 halflives
(whichever is shorter)
e. Any investigational agent received within 5 half-lives of the drug or 4
weeks, whichever is shorter. Concurrent participation in an
observational study may be allowed after review by the Sponsor's
Medical Monitor.
f. Patients with prior FGFR-directed therapy.
7. A serious illness or medical condition(s) including, but not limited to,
the following:
a. Known brain metastasis (not including primary brain tumors) unless patient is clinically stable for = 1 month.
b. Known acute systemic infection.
c. Myocardial infarction, severe/unstable angina, symptomatic
congestive heart failure (New York Heart Association [NYHA] Class III
or IV (see Appendix D, New York Heart Association [NYHA]
Classification) within the previous 2 months; if > 2 months, cardiac
function must be within normal limits and the patient must be free of
cardiac-related symptoms.
d. Chronic nausea, vomiting, or diarrhea considered to be clinically
significant in the opinion of the investigator.
e. Congenital long QT syndrome, or any known history of torsade de
pointes, or family history of unexplained sudden death.
f. Other severe acute or chronic medical or psychiatric condition or
laboratory abnormality that in the judgment of the investigator would
make the patient inappropriate for entry into this study.
8. Patients with a history of another primary malignancy that is
currently clinically significant, and has potential for meta

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified