An Open-label Phase I Study of Orally Available Novel Small-molecule Fibroblast Growth Factor Receptors (FGFR) 1,2,3 and 4 Inhibitor, ASP5878 at Single and Multiple Doses in Patients With Solid Tumors

NCT02038673 | Completed Phase 1 FDA Drug

• 1 other identifier: 5878-CL-0101
• Study Type: interventional
• Target: 86
• Locations: 4 countries
• Sites: 35

Brief Summary

The objectives of this study are to determine the tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of oral ASP5878 in participants with solid tumors.

Conditions

Solid Tumors

Keywords

ASP5878; FGFR 1,2,3 and 4 inhibitor

Outcome Measures

Primary Outcomes (9)

• Dose-escalation part and Expansion part: Safety assessed by Adverse Events (AEs)

  Until one of the discontinuation criteria is met.

  Up to 18 months

• Dose-escalation part and Expansion part:Safety assessed by Vital signs

  Blood pressure, pulse rate and body temperature, Until one of the discontinuation criteria is met.

  Up to 18 months

• Dose-escalation part and Expansion part:Safety assessed by Body weight

  Until one of the discontinuation criteria is met.

  Up to 18 months

• Dose-escalation part and Expansion part:Safety assessed by Laboratory tests

  Hematology, blood biochemistry, blood coagulation tests and urinalysis, until one of the discontinuation criteria is met.

  Up to 18 months

• Dose-escalation part and Expansion part:Safety assessed by 12-lead ECGs

  ECG: Electrocardiogram, until one of the discontinuation criteria is met.

  Up to 18 months

• Dose-escalation part and Expansion part: Ophthalmology

  Eyesight, funduscopy, slit lamp microscopy, and Optical Coherence Tomography, until one of the discontinuation criteria is met.

  Up to 18 months

• Dose-escalation part and Expansion part: Bone density measurement

  Until one of the discontinuation criteria is met.

  Up to 18 months

• Dose-escalation part and Expansion part: Computed tomography (CT) Imaging assessment

  Until one of the discontinuation criteria is met.

  Up to 18 months

• Expansion part only: Echocardiogram

  Until one of the discontinuation criteria is met.

  Up to 18 months

Secondary Outcomes (33)

• Dose-escalation part: Pharmacokinetics (PK) parameter of ASP5878 in plasma: Cmax

  Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1

• Dose-escalation part:PK parameter of ASP5878 in plasma: tmax

  Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1

• Dose-escalation part:PK parameter of ASP5878 in plasma: AUClast

  Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1

• Dose-escalation part: PK parameter of ASP5878 in plasma: AUCinf

  Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1

• Dose-escalation part: PK parameter of ASP5878 in plasma: t1/2

  Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1

Study Arms (12)

Dose escalation part 0.5 mg QD

EXPERIMENTAL

Oral

Drug: ASP5878

Dose escalation part 1.0 mg QD

EXPERIMENTAL

Oral

Drug: ASP5878

Dose escalation part 2.0 mg QD

EXPERIMENTAL

Oral

Drug: ASP5878

Dose escalation part 2.0 mg BID

EXPERIMENTAL

Oral

Drug: ASP5878

Dose escalation part 4.0 mg BID

EXPERIMENTAL

Oral

Drug: ASP5878

Dose escalation part 6.0 mg BID

EXPERIMENTAL

Oral

Drug: ASP5878

Dose escalation part 10.0 mg BID

EXPERIMENTAL

Oral

Drug: ASP5878

Dose escalation part 20.0 mg BID

EXPERIMENTAL

Oral

Drug: ASP5878

Dose escalation part 16.0 mg BID

EXPERIMENTAL

Oral

Drug: ASP5878

Expansion part Urothelial Carcinoma

EXPERIMENTAL

Oral

Drug: ASP5878

Expansion part Hepatocellular Carcinoma

EXPERIMENTAL

Oral

Drug: ASP5878

Expansion part Squamous Cell Lung Carcinoma

EXPERIMENTAL

Oral

Drug: ASP5878

Interventions

ASP5878 DRUG

oral

Dose escalation part 0.5 mg QD; Dose escalation part 1.0 mg QD; Dose escalation part 10.0 mg BID; Dose escalation part 16.0 mg BID; Dose escalation part 2.0 mg BID; Dose escalation part 2.0 mg QD; Dose escalation part 20.0 mg BID; Dose escalation part 4.0 mg BID; Dose escalation part 6.0 mg BID; Expansion part Hepatocellular Carcinoma; Expansion part Squamous Cell Lung Carcinoma; Expansion part Urothelial Carcinoma

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed solid tumor.
• Participant must meet at least one of the following criteria in the judgment of the investigator or sub-investigator:
• Disease progression despite standard therapies
• Progressive disease without any standard therapies established
• Standard therapies are considered intolerable
• Eastern Cooperative Oncology Group performance status 0 or 1.
• Predicted life expectancy ≥ 12 weeks in the judgment of the investigator or sub-investigator.

You may not qualify if:

• Participant with ≥ Grade 2 (CTCAE v 4.0-JCOG) persistent symptoms and objective findings due to the toxicity attributable to prior treatment with antitumor effect (except alopecia).
• Participant who received a prior treatment intended for antitumor effect (medication, surgery, radiotherapy, etc.) within 4 weeks prior to the planned first day of study drug dosing (or participant who received mitomycin C or Nitrosourea within 6 weeks prior to the planned first day of study drug dosing).
• A major surgical procedure within 4 weeks prior to the planned first day of study drug dosing or a surgical procedure is planned during the course of the study.
• Participant who were treated with other investigational drug or medical device within 4 weeks prior to the planned first day of study drug dosing.
• Participant who has a history of organ transplantation.
• Participant with a brain metastasis with symptoms or requiring treatment.

Sponsors & Collaborators

• Astellas Pharma Inc: lead
• Astellas Pharma Global Development, Inc.: collaborator

Study Sites (35)

Site US402

Orange, California, 92868, United States

Location

Site US401

New York, New York, 10032, United States

Location

Site US404

Cleveland, Ohio, 44106, United States

Location

Site US406

Spartanburg, South Carolina, 29303, United States

Location

Site US410

Fairfax, Virginia, 22031, United States

Location

Site US403

Seattle, Washington, 98109, United States

Location

Site JP122

Chiba, Japan

Location

Site JP108

Fukuoka, Japan

Location

Site JP115

Fukuoka, Japan

Location

Site JP120

Fukuoka, Japan

Location

Site JP116

Hokkaido, Japan

Location

Site JP113

Hyōgo, Japan

Location

Site JP103

Ibaraki, Japan

Location

Site JP111

Ishikawa, Japan

Location

Site JP119

Kanagawa, Japan

Location

Site JP101

Kyoto, Japan

Location

Site JP109

Miyagi, Japan

Location

Site JP110

Miyagi, Japan

Location

Site JP112

Nagoya, Japan

Location

Site JP117

Niigata, Japan

Location

Site JP121

Okayama, Japan

Location

Site JP104

Osaka, Japan

Location

Site JP106

Osaka, Japan

Location

Site JP118

Osaka, Japan

Location

Site JP124

Shizuoka, Japan

Location

Site JP102

Tokyo, Japan

Location

Site JP107

Tokyo, Japan

Location

Site JP123

Tokyo, Japan

Location

Site KR202

Gyeonggi-do, South Korea

Location

Site KR201

Seoul, South Korea

Location

Site KR203

Seoul, South Korea

Location

Site KR204

Seoul, South Korea

Location

Site TW302

Tainan, Taiwan

Location

Site TW301

Taipei, Taiwan

Location

Site TW303

Taipei, Taiwan

Location

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Interventions

ASP5878

Study Officials

• Medical Director

  Astellas Pharma Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: January 16, 2014
• Study Start: November 5, 2013
• Primary Completion: July 19, 2017
• Study Completion: July 19, 2017
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

JP (22); KR (4); US (6); TW (3)