A Phase 1 Study of LY2874455 in Participants With Advance... | NCT01212107

NCT01212107

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
I4R-MC-FGAA	Other Identifier	Eli Lilly and Company

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part A: 2 mg FGF Receptor QD	Experimental	Part A: Dose escalation 2 milligrams (mg) FGF receptor given orally once daily (QD) for a minimum of (1) 28 day cycle. If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days)	Drug: FGF Receptor
Part A: 4 mg FGF Receptor QD	Experimental	Part A: Dose escalation 4 mg FGF receptor given orally QD for a minimum of (1) 28 day cycle. If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days)	Drug: FGF Receptor
Part A: 10 mg FGF Receptor QD	Experimental	Part A: Dose escalation 10 mg FGF receptor given orally QD for a minimum of (1) 28 day cycle. If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days).	Drug: FGF Receptor
Part A: 10 mg FGF Receptor QD + Phosphate Binders	Experimental	Part A: Dose escalation 10 mg FGF receptor + phosphate binders given QD for a minimum of (1) 28 day cycle. If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days)	Drug: FGF Receptor Drug: Phosphate Binders
Part A: 8 mg FGF Receptor BID

Interventions

Name	Type	Description	Arm Group Labels	Other Names
FGF Receptor	Drug	LY2874455 administered orally.	Part A: 10 mg FGF Receptor BID Part A: 10 mg FGF Receptor QD Part A: 10 mg FGF Receptor QD + Phosphate Binders

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Recommended Dose for Phase 2 Studies : Maximum Tolerated Dose (MTD)	MTD was determined after the evaluation of Part A portion of the trial. Dose escalation proceeded at 1.3 times the preceding cohort once a Grade 3 non-laboratory toxicity or Grade 2 laboratory toxicity was noted in ≥ 1 participant until MTD was achieved. Doses up to 24 mg (48 mg/day) were evaluated in Part A. The effects at this dose and at 18 mg (36 mg/day) suggested that a reasonable number of participants might not tolerate LY2874455 for chronic administration at these dose levels because of the constellation of effects observed individually or in combination in participants at these dose levels. Therefore, the dose of 16 mg BID of LY2874455 (total dose 32 mg per day) was selected as the initial dose for Part B. Selection of the dose level was based on the tolerability of this dose and without specific toxicities identified.	Baseline Up to 32 Weeks

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events	Treatment-emergent adverse events (TEAEs) are events which were not present at baseline or pre-existing conditions at baseline that worsened in severity following the start of treatment. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have histological or cytological evidence of a diagnosis of cancer (solid tumors, lymphoma, or chronic lymphocytic leukemia) that is advanced and/or metastatic and for which all standard therapies have failed
Have the presence of measurable or non-measurable disease
Have given written informed consent prior to any study-specific procedures
Have adequate organ function including:
- Hematologic: Absolute neutrophil count (ANC) equal to or greater than 1.5 x 10(9)/L platelets equal to or greater than 100 x 10(9)/L, and hemoglobin equal to or greater than 8 g/dL. Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin until 14 days after the erythrocyte transfusion
- Hepatic: Bilirubin equal to or less than 1.5 times upper limits of normal (ULN), alanine transaminase (ALT), and aspartate transaminase (AST) equal to or less than 2.5 times ULN. If the liver has tumor involvement, AST and ALT equaling equal to or less than 5 times ULN are acceptable
- Renal: Serum creatinine less than or equal to 1.2 times ULN or calculated creatinine clearance greater than or equal to 60 milliliters per minute using the Standard Cockcroft and Gault Creatinine Clearance Calculation
- Calcium and phosphate less than or equal to 1.1 times ULN
Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale
Have discontinued chemotherapy and cancer-related hormonal therapy with commercially available agents for at least 21 days (6 weeks for mitomycin-C or nitrosoureas) and radiotherapy for at least 14 days prior to study enrollment and recovered from the acute effects of therapy. Hormone refractory prostate cancer participants receiving gonadotropin releasing hormone (GnRH) agonist therapy or breast cancer participants on antiestrogen therapy (for example, an aromatase inhibitor) prior to entrance on the study may have that treatment continued while they are enrolled in the study
Females with childbearing potential must have had a negative serum pregnancy test less than or equal to 7 days prior to the first dose of study drug. Males and females with reproductive potential must agree to use 2 medically approved contraceptive methods during the trial and for 3 months following the last dose of study drug. Female participants must agree to use 2 medically acceptable methods of contraception, 1 being an oral contraceptive, dermal patch, or progestin (implantation or injection), and the other being a medically acceptable barrier method; alternatively, 2 medically acceptable barrier methods may be used. Medically acceptable barrier methods of contraception that may be used by the participant and/or his/her partner include: abstinence; diaphragm with spermicide; intrauterine device (IUD); condom together with foam, spermicide, or vaginal spermicidal suppository. Prohibited methods include the rhythm method, withdrawal, condoms alone, or diaphragm alone
Have an estimated life expectancy of greater than or equal to 12 weeks

Exclusion Criteria:

Have received treatment with an investigational drug, which has not received regulatory approval for any indication, within 28 days of study treatment with LY2874455
Currently taking agents to control serum phosphate or calcium levels. This includes dietary restrictions
Have medical conditions that, in the opinion of the investigator, would preclude participation in this study
Have symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastases is not required
Have a history of major organ transplant (for example: heart, lungs, liver, and kidney)
Have current acute leukemia
Females who are pregnant or nursing
An untreated or uncontrolled acute infection, including urinary tract infection, within 7 days of study entry
Have Bazett's corrected QT (QTcB) greater than 470 msec (female) or greater than 450 msec (male), history of unexplained recurrent syncope, history of congenital long QT syndrome, family history of sudden death, or the presence in the screening electrocardiogram (ECG) of a conduction abnormality that in the opinion of the investigator would preclude safe participation in this study
Have had an autologous or allogenic bone marrow transplant
Previously treated with LY2874455

Contacts/Locations Module

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Locations

Facility	Status	City	State	ZIP	Country	Contacts
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.		East Melbourne	Victoria	3002

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28589492	Derived	Michael M, Bang YJ, Park YS, Kang YK, Kim TM, Hamid O, Thornton D, Tate SC, Raddad E, Tie J. A Phase 1 Study of LY2874455, an Oral Selective pan-FGFR Inhibitor, in Patients with Advanced Cancer. Target Oncol. 2017 Aug;12(4):463-474. doi: 10.1007/s11523-017-0502-9.

IPD Sharing Statement Module

A participant was defined as completer of the study after 2 cycles while a participant who discontinued was classified as a discontinuation prior to completing 2 cycles or a discontinuation after 2 cycles. Final disposition for the study is provided.

Arm/Group Information

ID	Title	Description
FG000	Part A: 2 mg FGF Receptor QD	Part A: Dose escalation 2 milligrams (mg) FGF receptor given orally once daily (QD) for a minimum of (1) 28 day cycle.
FG001	Part A: 4 mg FGF Receptor QD	Part A: Dose escalation 4 mg FGF receptor given orally QD for a minimum of (1) 28 day cycle.
FG002	Part A: 10 mg FGF Receptor QD	Part A: Dose escalation 10 mg FGF receptor given orally QD for a minimum of (1) 28 day cycle.
FG003	Part A: 10 mg FGF Receptor QD + Phosphate Binders	Part A: Dose escalation 10 mg FGF receptor + phosphate binders given QD for a minimum of (1) 28 day cycle.
FG004	Part A: 8 mg FGF Receptor BID	Part A: Dose escalation 8 mg of FGF receptor given orally twice a day (BID) for a minimum of (1) 28 day cycle.
FG005	Part A: 10 mg FGF Receptor BID	Part A: Dose escalation 10 mg FGF receptor given orally BID for a minimum of (1) 28 day cycle.
FG006	Part A: 14 mg FGF Receptor BID	Part A: Dose escalation 14 mg FGF receptor given orally BID for a minimum of (1) 28 day cycle.
FG007	Part A: 18 mg FGF Receptor BID	Part A: Dose escalation 18 mg FGF receptor given orally BID for a minimum of (1) 28 day cycle.
FG008	Part A: 24 mg FGF Receptor BID	Part A: Dose escalation 24 mg FGF receptor given orally BID for a minimum of (1) 28 day cycle.
FG009	Part A: 18 mg FGF Receptor BID Extension	Part A: Dose escalation 18 mg FGF Receptor given orally BID for a minimum of (1) 28 day cycle.
FG010	Part A: 16 mg FGF Receptor BID	Part A: Dose escalation 16 mg FGF Receptor given orally BID for a minimum of (1) 28 day cycle
FG011	Part B: 16 mg FGF Receptor BID (NSCLS & Gastric Cancer)	Part B: Dose determined by part a dose escalation 16 mg FGF Receptor given orally BID for a minimum of (1) 28 day cycle.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0003 subjects FG0013 subjects FG0026 subjects FG0033 subjects FG0043 subjects FG0053 subjects FG0063 subjects FG0073 subjects FG0083 subjects FG0093 subjects FG0103 subjects FG01158 subjects
COMPLETED		FG0002 subjects FG0012 subjects FG0023 subjects FG0033 subjects FG004
NOT COMPLETED		FG0001 subjects FG0011 subjects FG0023 subjects FG0030 subjects FG004

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Part A: 2 mg FGF Receptor QD	Part A: Dose escalation 2 milligrams (mg) FGF receptor given orally once daily (QD) for a minimum of (1) 28 day cycle.
BG001	Part A: 4 mg FGF Receptor QD

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Recommended Dose for Phase 2 Studies : Maximum Tolerated Dose (MTD)

MTD was determined after the evaluation of Part A portion of the trial. Dose escalation proceeded at 1.3 times the preceding cohort once a Grade 3 non-laboratory toxicity or Grade 2 laboratory toxicity was noted in ≥ 1 participant until MTD was achieved. Doses up to 24 mg (48 mg/day) were evaluated in Part A. The effects at this dose and at 18 mg (36 mg/day) suggested that a reasonable number of participants might not tolerate LY2874455 for chronic administration at these dose levels because of the constellation of effects observed individually or in combination in participants at these dose levels. Therefore, the dose of 16 mg BID of LY2874455 (total dose 32 mg per day) was selected as the initial dose for Part B. Selection of the dose level was based on the tolerability of this dose and without specific toxicities identified.

All participants who received at least one dose of study drug in Part A.

Posted

Number

Baseline Up to 32 Weeks

ID	Title	Description
OG000

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A: 2 mg FGF Receptor QD	Part A: Dose escalation 2 milligrams (mg) FGF receptor given orally once daily (QD) for a minimum of (1) 28 day cycle.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Chorioretinopathy	Eye disorders	MedDRA 14.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Chief Medical Officer	Eli Lilly and Company	800-545-5979		ClinicalTrials.gov@lilly.com

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D009362	Neoplasm Metastasis
D009369	Neoplasms

ID	Term
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

Intervention Browse Module

ID	Term
D017468	Receptors, Fibroblast Growth Factor
C570663	2-(4-(2-(5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazol-3yl)vinyl)-1H-pyrazol-1-yl)ethanol

ID	Term
D017978	Receptors, Growth Factor
D018000	Receptors, Peptide
D011956	Receptors, Cell Surface
D008565	Membrane Proteins

Masking Info

Part A: 14 mg FGF Receptor BID

Part A: 16 mg FGF Receptor BID

Part A: 18 mg FGF Receptor BID

Part A: 18 mg FGF Receptor BID Extension

Part A: 2 mg FGF Receptor QD

Part A: 24 mg FGF Receptor BID

Part A: 4 mg FGF Receptor QD

Part A: 8 mg FGF Receptor BID

Part B: 16 mg FGF Receptor BID

Part A: Dose escalation 4 mg FGF receptor given orally QD for a minimum of (1) 28 day cycle.

EG0000 events0 affected3 at risk

EG0010 events0 affected3 at risk

EG0020 events0 affected6 at risk

EG0030 events0 affected3 at risk

EG0040 events0 affected3 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected3 at risk

EG0080 events0 affected3 at risk

EG0090 events0 affected3 at risk

EG0100 events0 affected3 at risk

EG0111 events1 affected58 at risk

EG0000 events0 affected3 at risk

EG0010 events0 affected3 at risk

EG0025 events1 affected6 at risk

EG0030 events0 affected3 at risk

EG0040 events0 affected3 at risk

EG0050 events0 affected3 at risk

EG0061 events1 affected3 at risk

EG0070 events0 affected3 at risk

EG0080 events0 affected3 at risk

EG0090 events0 affected3 at risk

EG0100 events0 affected3 at risk

EG0117 events5 affected58 at risk

OG008127± NAn=1 only Geometric Mean available

OG008500± NAn=1 only Geometric Mean calculable