A Study for Participants With Metastatic Renal Cell Carcinoma

NCT00709995 | Completed Phase 2 Results

• 2 other identifiers: 11531H6Q-MC-S061
• Study Type: interventional
• Target: 17
• Locations: 4 countries
• Sites: 4

Brief Summary

This study will compare the effects of Enzastaurin plus Sunitinib versus Sunitinib alone in metastatic Renal Cell Cancer.

Conditions

Metastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) in Part 2

  Progression-free survival (PFS) was defined as the number of months between the date of randomization and the date of first documented disease progression or the date of death due to any cause, whichever came first.

  Randomization to Measured Progressive Disease (PD) (Up to 24 Months)

Secondary Outcomes (5)

• Overall Survival (OS) in Part 2

  Randomization to Death from Any Cause (Up to 24 Months)

• Time-To-Tumor Progression in Part 2

  Randomization to the Date of Objective Progressive Disease or Date of Death due to Study Disease, whichever came first (Up to 24 Months)

• Number of Participants With Adverse Events (AEs) or Serious AEs (SAEs) in Part 1

  Randomization to Study Completion (Up to 6 Cycles)

• Pharmacokinetics (PK): Area Under Concentration Time Curve During One Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin + Metabolite (LSN326020) + Total Analytes in Part 1

  Cycle 1 Day 15: Predose, 2, 4, and 6 - 8 hours, Up to 12 Hours Post dose

• PK: Maximum Concentration at Steady State (Cmax,ss) of Enzastaurin + LSN326020 + Total Analytes in Part 1

  Cycle 1 Day 15: Predose, 2, 4, and 6 - 8 hours, Up to 12 Hours Post dose

Study Arms (2)

Part 1 Arm A: Enzastaurin + Sunitinib

EXPERIMENTAL

(Cohort 1): On cycle 1, day 1 a loading dose 125 milligram (mg) of Enzastaurin was administered by mouth orally, (BID) twice a day, followed by Enzastaurin 125 mg administered, twice a day, Days 2 through 42 of a 6-week cycle. (Cohort 2): Cycle 1, Day 1 loading dose 375 mg of Enzastaurin administered po three times a day (TID), followed by 250 mg, po, BID continuously until disease progression, unacceptable toxicity, death, or discontinuation from the study for any other reason. Sunitinib 50 mg was administered orally, once daily, Days 1-28, then rest (no drug given) days 29-42. Phase 2 (Part 2): Randomized Double-Blind: Dosing was determined by Part 1. Part 2 was not activated per recommendation of safety review committee. Enzastaurin: Cycle 1, Day 1 loading dose 375 mg administered orally, (TID) three times a day, followed by Part 1 dose twice a day on Days 2-42 of 6 week cycle. Sunitinib: 50 mg administered orally, once daily, on Days 1-28, then rest Days 29-42.

Drug: Enzastaurin; Drug: Sunitinib

Part 2 Arm B: Sunitinib + Placebo

PLACEBO COMPARATOR

Part 2 was not activated per recommendation of safety review committee. Sunitinib: 50 mg administered orally, once daily, Day 1-28, then rest Days 29-42. Placebo: Cycle 1 Day 1 loading dose 3 tablets on Day 1, then 2 tablets daily, days 2-42.

Drug: Sunitinib; Drug: Placebo

Interventions

Enzastaurin DRUG

Administered orally

Also known as: LY317615

Part 1 Arm A: Enzastaurin + Sunitinib

Sunitinib DRUG

Administered orally

Part 1 Arm A: Enzastaurin + Sunitinib; Part 2 Arm B: Sunitinib + Placebo

Placebo DRUG

Administered orally

Part 2 Arm B: Sunitinib + Placebo

Eligibility Criteria

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

You may qualify if:

• Participants with metastatic Renal Cell Carcinoma (RCC) who have not received prior treatment with systemic (adjuvant or neoadjuvant) therapy for RCC (including targeted therapy such as tyrosine kinase inhibitors or bevacizumab, immunotherapy, chemotherapy, hormonal, or investigational therapy)
• Histologically confirmed RCC with metastases with a component of clear (conventional) cell histology
• Evidence of unidimensional measurable disease, measured by computed tomography (CT) scan or magnetic resonance imaging (MRI)
• Primary tumor has been surgically removed by nephrectomy or nephron-sparing surgery
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Participants must sign an informed consent document

You may not qualify if:

• Have received prior treatment with sunitinib or enzastaurin
• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
• Have had any of the following within 12 months prior to study drug administration:
• myocardial infarction,
• severe/unstable angina,
• coronary/peripheral artery bypass graft,
• symptomatic congestive heart failure (CHF),
• cerebrovascular accident,
• transient ischemic attack, or
• pulmonary embolism
• Note: Ongoing treatment with therapeutic doses of Coumadin® (warfarin) or a derivative of Coumadin or phenprocoumon is not allowed, but prophylactic, low-dose Coumadin (≤ 2 mg daily) for deep vein thrombosis is allowed. In such cases, prothrombin time/international normalization ratio (PT/INR) should be very closely monitored as clinically indicated
• Ongoing cardiac arrhythmias \>New York Health Association Class II, atrial fibrillation of any grade, or prolongation of the QTc interval to \>450 millisecond (msec) for males or \>470 msec for females.
• Have uncontrolled hypertension \[\>150/100 millimeter of mercury (mm/Hg) despite optimal medical therapy\], or history of poor compliance with antihypertensive treatment
• Require concomitant use of potent Cytochrome P450 3A4 (CYP3A4) inducer, for example, rifampicin or potent CYP3A inhibitors, such as ketoconazole.
• Significant surgery or radiation therapy \<4 weeks of starting study treatment. Prior palliative radiotherapy to metastatic lesion(s) is/are permitted, provided there is at least 1 measurable lesion that has not been irradiated

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (4)

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.

Vienna, A1090, Austria

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.

Villejuif, 94805, France

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.

Rome, 00149, Italy

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.

Warsaw, 00909, Poland

Location

Related Links

• Lilly Clinical Trial Registry

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

enzastaurin; Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Part 1 completers finished 3 or more cycles and included those with progressive disease. Part 2 was not performed and was not activated due to sponsor broad decision to not pursue enzastaurin in solid tumors

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) Mon - Fri 9AM - 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 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2008
• First Posted: July 3, 2008
• Study Start: June 30, 2008
• Primary Completion: February 15, 2010
• Study Completion: September 5, 2018
• Last Updated: September 30, 2019
• Results First Posted: September 30, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

PL (1); FR (1); AU (1); IT (1)