A Study of LY2874455 in Patients With Advanced Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01212107
First received: September 16, 2010
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

The study is to determine the recommended Phase 2 regimen of study drug that may be safely administered to patients with advanced and or metastatic cancer. The study consists of two parts: a dose escalation and a dose confirmation.


Condition Intervention Phase
Advanced Cancer
Drug: LY2874455
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of LY2874455 to Assess Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy in Patients With Advanced Cancer.

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Recommended dose for Phase 2 studies [ Time Frame: Baseline to study completion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants with clinically significant effects [ Time Frame: Baseline to study completion ] [ Designated as safety issue: Yes ]
  • Tumor measurement (palpable or visible) [ Time Frame: Baseline, Cycle 1 Day-1, then each cycle until study completion Day 28, Follow-up Visit ] [ Designated as safety issue: No ]
  • Radiological tumor measurement [ Time Frame: Baseline, completed prior to every other Cycle beginning with Cycle 3, Follow-up Visit ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) of LY2874455, maximum concentration (Cmax) [ Time Frame: Part A: Cycle 1 Day -1, Cycle 1 Day-28, Part B: Cycle 1 Day-1, Cycle 1 Day-28 ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) of LY2874455, area under the concentration-time curve (AUC) [ Time Frame: Part A: Cycle 1 Day 1, Cycle 1 Day-28, Part B: Cycle 1 Day-1, Cycle 1 Day-28 ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: December 2010
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2 mg LY2874455
2 mg LY287445 administered orally once daily for a minimum of (1) 28 day cycle
Drug: LY2874455

LY2874455 will be taken orally (capsules) once or twice daily for a minimum of (1) 28 day cycle.

Part A: dose escalation

2-200 mg, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

Part B: dose confirmation

dose determined by Part A dose escalation, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

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

Experimental: 4 mg LY2874455
4 mg LY2874455 administered orally once daily for a minimum of (1) 28 day cycle
Drug: LY2874455

LY2874455 will be taken orally (capsules) once or twice daily for a minimum of (1) 28 day cycle.

Part A: dose escalation

2-200 mg, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

Part B: dose confirmation

dose determined by Part A dose escalation, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

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

Experimental: 10 mg LY287445
10 mg LY2874455 administered orally once daily for a minimum of (1) 28 day cycle
Drug: LY2874455

LY2874455 will be taken orally (capsules) once or twice daily for a minimum of (1) 28 day cycle.

Part A: dose escalation

2-200 mg, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

Part B: dose confirmation

dose determined by Part A dose escalation, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

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

Experimental: 16 mg LY2874455
8 mg LY2874455 administered orally twice daily for a minimum of (1) 28 day cycle
Drug: LY2874455

LY2874455 will be taken orally (capsules) once or twice daily for a minimum of (1) 28 day cycle.

Part A: dose escalation

2-200 mg, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

Part B: dose confirmation

dose determined by Part A dose escalation, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

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

Experimental: 20 to 24 mg LY2874455
10 to 12 mg of LY2874455 administered orally twice daily for a minimum of (1) 28 day cycle
Drug: LY2874455

LY2874455 will be taken orally (capsules) once or twice daily for a minimum of (1) 28 day cycle.

Part A: dose escalation

2-200 mg, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

Part B: dose confirmation

dose determined by Part A dose escalation, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

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

Experimental: 24 to 36 mg LY2874455
12 to 18 mg LY2874455 administered orally twice daily for a minimum of (1) 28 day cycle
Drug: LY2874455

LY2874455 will be taken orally (capsules) once or twice daily for a minimum of (1) 28 day cycle.

Part A: dose escalation

2-200 mg, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

Part B: dose confirmation

dose determined by Part A dose escalation, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

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

Experimental: 28 to 56 mg LY2874455
14 to 28 mg LY2874455 administered orally twice daily for a minimum of (1) 28 day cycle
Drug: LY2874455

LY2874455 will be taken orally (capsules) once or twice daily for a minimum of (1) 28 day cycle.

Part A: dose escalation

2-200 mg, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

Part B: dose confirmation

dose determined by Part A dose escalation, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

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

Experimental: 36 to 94 mg LY2874455
18 to 42 mg LY2874455 administered orally twice daily for a minimum of (1) 28 day cycle
Drug: LY2874455

LY2874455 will be taken orally (capsules) once or twice daily for a minimum of (1) 28 day cycle.

Part A: dose escalation

2-200 mg, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

Part B: dose confirmation

dose determined by Part A dose escalation, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

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

Experimental: 44 to 128 mg LY2874455
22 to 64 mg LY2874455 administered orally twice daily for a minimum of (1) 28 day cycle
Drug: LY2874455

LY2874455 will be taken orally (capsules) once or twice daily for a minimum of (1) 28 day cycle.

Part A: dose escalation

2-200 mg, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

Part B: dose confirmation

dose determined by Part A dose escalation, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

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

Experimental: 56 to 192 mg LY2874455
28 to 96 mg LY2874455 administered orally, twice daily for a minimum of (1) 28 day cycle
Drug: LY2874455

LY2874455 will be taken orally (capsules) once or twice daily for a minimum of (1) 28 day cycle.

Part A: dose escalation

2-200 mg, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

Part B: dose confirmation

dose determined by Part A dose escalation, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

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

Experimental: 72 to 200 mg LY2874455
36 to 100 mg LY2874455 administered orally twice daily for a minimum of (1) 28 day cycle
Drug: LY2874455

LY2874455 will be taken orally (capsules) once or twice daily for a minimum of (1) 28 day cycle.

Part A: dose escalation

2-200 mg, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

Part B: dose confirmation

dose determined by Part A dose escalation, administered orally, once or twice daily for a minimum of one (1) 28 day cycle

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


Detailed Description:

Phase 1, first human dose study

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 nonmeasurable 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. Patients 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 patients receiving gonadotropin releasing hormone (GnRH) agonist therapy or breast cancer patients 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 patients 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. Patients 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 patients 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 and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01212107

Locations
Australia, Victoria
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, 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
Korea, Republic of
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, Korea, Republic of, 110-744
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01212107     History of Changes
Other Study ID Numbers: 13843, I4R-MC-FGAA
Study First Received: September 16, 2010
Last Updated: May 12, 2014
Health Authority: Australia: National Health and Medical Research Council
Korea: Ministry of Food and Drug Safety
United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Advanced cancer
Metastatic cancer
Oncology

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on September 18, 2014