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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01212107




Registration number
NCT01212107
Ethics application status
Date submitted
16/09/2010
Date registered
30/09/2010
Date last updated
12/06/2019

Titles & IDs
Public title
A Phase 1 Study of LY2874455 in Participants With Advanced Cancer
Scientific title
A Phase 1 Study of LY2874455 to Assess Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy in Patients With Advanced Cancer.
Secondary ID [1] 0 0
I4R-MC-FGAA
Secondary ID [2] 0 0
13843
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - FGF Receptor
Treatment: Drugs - Phosphate Binders

Experimental: 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.
If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days)

Experimental: 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.
If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days)

Experimental: 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.
If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days).

Experimental: 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.
If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days)

Experimental: 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.
If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days)

Experimental: 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.
If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days)

Experimental: Part A: 14 mg FGF Receptor BID - Part A: Dose escalation
14 FGF receptor given orally BID 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)

Experimental: 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.
If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days)

Experimental: 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.
If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days).

Experimental: 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.
If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days)

Experimental: 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.
If participants are determined to be receiving benefit, study treatment may be continued for up to one (1) year (12 cycles of 28 days)

Experimental: Part B: 16 mg FGF Receptor BID - Part B: Dose determined by part a dose escalation
16 mg FGF Receptor given orally BID 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)


Treatment: Drugs: FGF Receptor
LY2874455 administered orally.

Treatment: Drugs: Phosphate Binders
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Dose for Phase 2 Studies : Maximum Tolerated Dose (MTD)
Timepoint [1] 0 0
Baseline Up to 32 Weeks
Secondary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events
Timepoint [1] 0 0
Baseline Up to 60 Weeks
Secondary outcome [2] 0 0
Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR)
Timepoint [2] 0 0
BORR: Baseline Up to 60 Weeks ; ORR: Baseline Up to 60 Weeks
Secondary outcome [3] 0 0
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455
Timepoint [3] 0 0
Part A and B: Cycle 1, Day 1, Pre-Dose, 0.5 Hr (H), 1 H, 2 H, 4H,8 H,12 H,24 H; Day 28, Pre-Dose, 0.5 H, 1 H, 2 H, 4 H, 8 H
Secondary outcome [4] 0 0
Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455
Timepoint [4] 0 0
Part A and B: Cycle 1, Day 1, Pre-Dose, 0.5 Hr (H), 1 H, 2 H, 4H,8 H,12 H,24 H; Day 28, Pre-Dose, 0.5 H, 1 H, 2 H, 4 H, 8 H

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2015
Sample size
Target
Accrual to date
Final
94
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
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
Recruitment hospital [2] 0 0
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. - Parkville
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
Korea, Republic of
State/province [1] 0 0
Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The study is to determine the recommended Phase 2 regimen of study drug that may be safely
administered to participants with advanced and or metastatic cancer. The study consists of
two parts: a dose escalation and a dose confirmation.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01212107
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01212107