A Study of LY2584702 in Participants With Advanced Cancer

NCT01394003 | Terminated Phase 1 Results

• 2 other identifiers: 12451I3G-MC-JGCA
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

The main purpose of this trial is to determine a recommended Phase 2 dose of LY2584702 that may be safely administered to participants with advanced/metastatic cancer.

Conditions

Advanced Cancer

Keywords

Advanced cancer

Outcome Measures

Primary Outcomes (1)

• Recommended Dose for Phase 2 Studies/Maximum Tolerated Dose (MTD)

  Based on the maximum tolerated dose (MTD): highest dose where \<33% participants experienced a dose-limiting toxicity (DLT). DLTs were adverse events (AEs) during Cycle 1 that met any 1 of the following criteria using National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE) grading: any ≥Grade 3 nonhematological toxicity (except nausea/vomiting, diarrhea or hypophosphatemia without maximal symptomatic/prophylactic treatment) that was not related to study disease, any ≥Grade 3 thrombocytopenia with bleeding, any Grade 4 hematological toxicity of \>5 days duration or any febrile neutropenia. Investigators, together with the sponsor, could declare a DLT during Cycle 1 if a participant experienced increasing toxicity and it was clear that further treatment would expose the participant to excessive risk. The MTD was below the level required for efficacy, therefore, the study was terminated early and the recommended Phase 2 dose was not calculated.

  Parts A and B, Baseline through Cycle 1 (1 cycle=28 days)

Secondary Outcomes (4)

• Pharmacokinetics, Maximum Plasma Concentration (Cmax)

  Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, 8 hours postdose)

• Number of Participants With Tumor Response

  Parts A and B, Baseline through study completion [up to Cycle 10 (1 cycle=28 days)]

• Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing

  Part A, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose)

• Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing

  Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose)

Study Arms (1)

LY2584702

EXPERIMENTAL

Oral dose escalation starting at 25 milligrams (mg), daily for 28 day cycles in Part A; oral dose escalation starting at 50 mg, twice daily for 28 day cycles in Part B; oral dose with schedule determined by Parts A and B will be administered in Part C (dose confirmation). Part A: Participants received 25 mg, 50 mg, 100 mg and 200 mg once daily (QD) and 300 mg twice daily (BID) of LY2584702 capsule, for a 28-day cycle during Part A of the study until the criteria for maximum tolerated dose (MTD) were met. Part B: Participants received 50 mg, 75 mg and 100 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until the criteria for maximum tolerated dose (MTD) were met.

Drug: LY2584702

Interventions

LY2584702 DRUG

administered orally

LY2584702

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 advanced and/or metastatic cancer (solid tumors) that is refractory to standard therapy and/or therapies known to provide clinical benefit, or for which no standard therapy exists
• Have the presence of disease amenable to efficacy assessment as defined by the Response Evaluation Criteria in Solid Tumors. Participants who have advanced non-measurable disease with elevation of a validated tumor marker may be eligible, if discussed and agreed upon by the investigator and the sponsor
• Participants entering Part C of the study must have a tumor that is safely amenable to 2 biopsies (one pre-treatment and one on-treatment biopsy for the same tumor). Participants in Part C of the study must agree to biopsy procedures at time of consent
• Have adequate hematologic, renal, and hepatic organ function
• Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
• Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy (with the exception of continuing gonadotropic releasing hormone (GnRH) agonist therapy for participants with prostate cancer, or anti-estrogen therapy \[for example, an aromatase inhibitor\] for participants with breast cancer), or other investigational therapy for at least 3 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy
• Are reliable and willing to be available for the duration of the study and are willing to follow study procedures
• Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug
• Females with child bearing potential must have had a negative serum pregnancy test less than or equal to 7 days prior to the first dose of study drug
• Have an estimated life expectancy of greater than or equal to 12 weeks
• Are able to swallow capsules

You may not qualify if:

• Have received treatment within 3 weeks of the initial dose of study drug with a drug that has not received regulatory approval for any indication
• Have 1 or more serious preexisting 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 metastasis is not required
• Have hematologic malignancies, or lymphoma
• Females who are pregnant or lactating
• Have a second primary malignancy that, in the judgement of the investigator and sponsor, may affect the interpretation of results
• Have bleeding diathesis

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (2)

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.

Santa Monica, California, United States

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.

San Antonio, Texas, United States

Location

Related Publications (1)

• Tolcher A, Goldman J, Patnaik A, Papadopoulos KP, Westwood P, Kelly CS, Bumgardner W, Sams L, Geeganage S, Wang T, Capen AR, Huang J, Joseph S, Miller J, Benhadji KA, Brail LH, Rosen LS. A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumours. Eur J Cancer. 2014 Mar;50(5):867-75. doi: 10.1016/j.ejca.2013.11.039. Epub 2014 Jan 15.

  PMID: 24440085 DERIVED

MeSH Terms

Interventions

LY2584702

Limitations and Caveats

Part C of the study was terminated because exposure at the maximum tolerated dose (MTD) was determined to be below the level required for efficacy.

Results Point of Contact

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

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-817-285-4559) or 1-317-615-4559 Mon-Fri 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
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2011
• First Posted: July 14, 2011
• Study Start: November 1, 2008
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: January 18, 2019
• Results First Posted: January 18, 2019

Record last verified: 2018-08

Locations

US (2)