A Phase 1 Study of LY2874455 in Participants With Advanced Cancer

NCT ID: NCT01212107

Last Updated: 2019-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2015-02-28

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.

Detailed Description

Phase 1, first human dose study

Conditions

Advanced Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

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)

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

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).

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

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)

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

Phosphate Binders

Intervention Type: DRUG

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)

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

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)

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

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)

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

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)

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

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).

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

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)

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

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)

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

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)

Group Type: EXPERIMENTAL

FGF Receptor

Intervention Type: DRUG

LY2874455 administered orally.

Interventions

FGF Receptor

LY2874455 administered orally.

Intervention Type: DRUG

Phosphate Binders

Intervention Type: DRUG

Other Intervention Names

LY2874455

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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, Australia

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

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.

Seoul, , South Korea

Countries

Australia; South Korea

References

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.

Reference Type: DERIVED

PMID: 28589492 (View on PubMed)

Other Identifiers

I4R-MC-FGAA

Identifier Type: OTHER

Identifier Source: secondary_id

13843

Identifier Type: -

Identifier Source: org_study_id