A Phase 1 Study of LY2874455 in Participants With Advanced Cancer

June 11, 2019 updated by: Eli Lilly and Company

A Phase 1 Study of LY2874455 to Assess Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy in Patients With Advanced Cancer.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Phase 1, first human dose study

Study Type

Interventional

Enrollment (Actual)

94

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • 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, Victoria, Australia, 3050
        • 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.
  • Korea, Republic of
      • Seoul, Korea, Republic of, 110-744
        • 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.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455
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)
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455
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).
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455
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)
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455
Drug: Phosphate Binders
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)
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455
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)
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455
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)
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455
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)
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455
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).
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455
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)
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455
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)
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455
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)
Drug: FGF Receptor
LY2874455 administered orally.
Other Names:
  • LY2874455

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recommended Dose for Phase 2 Studies : Maximum Tolerated Dose (MTD)
Time Frame: Baseline Up to 32 Weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events
Time Frame: Baseline Up to 60 Weeks
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.
Baseline Up to 60 Weeks
Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR)
Time Frame: BORR: Baseline Up to 60 Weeks ; ORR: Baseline Up to 60 Weeks

BORR is evaluated using response evaluation criteria in solid tumors (RECIST, version 1.1) criteria. Complete Response (CR): disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter.

Best overall response rate = (unconfirmed CR+ unconfirmed PR) / subjects in efficacy population.

Objective response rate = (confirmed CR+ confirmed PR) / subjects in efficacy population.
BORR: Baseline Up to 60 Weeks ; ORR: Baseline Up to 60 Weeks
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455
Time Frame: 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
Maximum observed concentration during a dosing interval.
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
Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455
Time Frame: 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
Area under the concentration-time curve from time 0 to the end of the dosing interval (e.g., BID) calculated by a combination of linear and logarithmic trapezoidal methods (linear-up/log-down method).
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2010

Primary Completion (ACTUAL)

August 1, 2014

Study Completion (ACTUAL)

February 1, 2015

Study Registration Dates

First Submitted

September 16, 2010

First Submitted That Met QC Criteria

September 29, 2010

First Posted (ESTIMATE)

September 30, 2010

Study Record Updates

Last Update Posted (ACTUAL)

June 12, 2019

Last Update Submitted That Met QC Criteria

June 11, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13843
  • I4R-MC-FGAA (OTHER: Eli Lilly and Company)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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