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

Phase 1

• Conditions: Advanced solid tumors; MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-12-12
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 385

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, it is requested
that 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; it is requested that patients enrolled on this basis
provide tumor tissues to Foundation Medicine if available from either
archival samples or fresh tumor biopsy.
ii. Patient has been treated with at least one prior systemic gemcitabine
and platinum-based chemotherapy. Patients with prior adjuvant
gemcitabine-platinum chemotherapy are eligible if the patient had
recurrence within 6 months of the last dose of the regimen.
iii. Patient has documentation of radiographic disease progression on
the most recent prior therapy
4. Patient has measurable disease as defined by Response Evaluation
Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for
advanced solid tumors or RANO criteria (2010) for brain tumors.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or
1 on Day 1 of Cycle 1
6. Able to take medications orally
7. Adequate organ function as defined by the following criteria:
a. Aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) = 3.0 ×upper limit of normal (ULN); if liver function abnormalities
are due to underlying liver metast

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 half-lives (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 metastases or currently requires active intervention (except for gonadotropin-releasing hormone (GnRH) or luteinizing hormone-releasing hormone (LH-RH) agonists in prostate cancer or adjuvant hormonal therapy in breast cancer).
9.Pregnant or lactating female.

Study & Design

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