A Phase 1 Study of LY2874455 in Participants With Advanced Cancer

NCT01212107 | Completed Phase 1 Results DMC

• 2 other identifiers: 13843I4R-MC-FGAA
• Study Type: interventional
• Target: 94
• Locations: 2 countries
• Sites: 3

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.

Conditions

Advanced Cancer

Keywords

Advanced cancer; Metastatic cancer; Oncology

Outcome Measures

Primary Outcomes (1)

• 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 (4)

• Number of Participants With Treatment-Emergent Adverse Events

  Baseline Up to 60 Weeks

• Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR)

  BORR: Baseline Up to 60 Weeks ; ORR: Baseline Up to 60 Weeks

• Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455

  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

  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

Study Arms (12)

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

EXPERIMENTAL

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

Part A: 10 mg FGF Receptor BID

EXPERIMENTAL

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

Part A: 14 mg FGF Receptor BID

EXPERIMENTAL

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

Part A: 18 mg FGF Receptor BID

EXPERIMENTAL

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

Part A: 24 mg FGF Receptor BID

EXPERIMENTAL

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

Part A: 18 mg FGF Receptor BID Extension

EXPERIMENTAL

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

Part A: 16 mg FGF Receptor BID

EXPERIMENTAL

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

Part B: 16 mg FGF Receptor BID

EXPERIMENTAL

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

Interventions

FGF Receptor DRUG

LY2874455 administered orally.

Also known as: LY2874455

Part A: 10 mg FGF Receptor BID; Part A: 10 mg FGF Receptor QD; Part A: 10 mg FGF Receptor QD + Phosphate Binders; 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

Phosphate Binders DRUG

Part A: 10 mg FGF Receptor QD + Phosphate Binders

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

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, Australia

Location

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, 3050, Australia

Location

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, 110-744, South Korea

Location

Related Publications (1)

• 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.

  PMID: 28589492 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

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

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Receptors, Growth Factor; Receptors, Peptide; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 16, 2010
• First Posted: September 30, 2010
• Study Start: December 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: February 1, 2015
• Last Updated: June 12, 2019
• Results First Posted: June 12, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); KR (1)