A Study for Participants With Metastatic Renal Cell Carcinoma

Lilly

Status and phase: Completed; Phase 2

Conditions: Metastatic Renal Cell Carcinoma

Treatments: Drug: Sunitinib; Drug: Enzastaurin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00709995

11531

H6Q-MC-S061 (Other Identifier)

Details and patient eligibility

About

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

Full description

This is a multicenter, Phase 2 study of enzastaurin and sunitinib versus placebo and sunitinib as first-line therapy in participants with metastatic renal cell carcinoma, containing 2 parts. Part 1 is a safety lead-in study with 12 participants and possible dose escalation. Part 2 is a randomized, double-blind, Phase 2 study in 110 participants.

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

• Participants who are pregnant or breast feeding

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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17 participants in 2 patient groups, including a placebo group

Part 1 Arm A: Enzastaurin + Sunitinib

Experimental group

Description:

(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.

Treatment:

Drug: Sunitinib

Drug: Enzastaurin

Part 2 Arm B: Sunitinib + Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Sunitinib