Clinical trial NCT01258348: A Phase 1b Trial in Patients With Renal Cell Cancer
Official title: A Phase 1b Study of LY573636-sodium in Combination With Sunitinib Malate in Patients With Metastatic Renal Cell Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Renal Cell Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-12-10
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine a safe dose of LY573636-sodium to be given in combination with sunitinib to patients with metastatic Renal Cell Carcinoma (RCC) and to determine any side effects that may be associated with LY573636-sodium and sunitinib combination in this patient population. The tumor response rate will also be assessed.


Eligibility criteria: Inclusion Criteria:

* Participants must have a histologically confirmed diagnosis of metastatic Renal Cell Carcinoma (RCC)
* Participants must have received no prior treatment with a cytotoxic-based chemotherapy regimen
* Participants must have measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines
* Have adequate hematologic, hepatic and renal function
* Have a serum albumin level greater than equal to 3.0 grams/Liter (g/L)
* Participants with reproductive potential should use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug
* Exhibit participant compliance and geographic proximity that allow for adequate follow-up
* Have given written informed consent approved by Lilly and the ethical review board (ERB)/institutional review board (IRB) governing the site
* Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy, for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy (except alopecia). Participants who have received whole-brain radiation must wait 90 days before starting study therapy

Exclusion Criteria:

* 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 received a prior cytotoxic chemotherapy-based systemic therapy for metastatic RCC
* Have had any of the following within 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure (CHF), cerebrovascular accident, transient ischemic attack, or pulmonary embolism
* Ongoing cardiac arrhythmias greater than New York Health Association Class II (Protocol Attachment JZAI.4), atrial fibrillation of any grade, or prolongation of the QTc interval to greater than 450 milliseconds (msec) for males or greater than 470 msec for females
* Have uncontrolled hypertension \[greater than 150/100 millimeters of mercury (mm Hg) despite optimal medical therapy\], or history of poor compliance with antihypertensive treatment
* Participants with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before study entry
* Participants with serious concomitant OR pre-existing disorders, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the investigator)
* Participants receiving warfarin therapy for treatment of venous thrombosis or other prothrombotic conditions
* Participants with a second primary malignancy that could affect interpretation of the results. NOTE: Participants with adequately treated carcinoma of the skin (excluding melanoma) and participants with a prior history of malignancy who have been disease-free for greater than 2 years are eligible
* Participants who have previously completed or withdrawn from this study or any other study investigating LY573636
* Participants who have previously received sunitinib
* Participants who are unable to swallow capsules
* Participants who require concomitant use of potent Cytochrome P450 3A4 (CYP3A4) inducers or inhibitors
* Women who are pregnant or lactating

Primary outcomes:
measure: Recommended Dose for Phase 2 Studies of LY573636-Sodium Combined With Sunitinib in Participants With Metastatic Renal Cell Carcinoma
timeFrame: Predose up to 42 days postdose in Cycle 1 (6 weeks per cycle)
Secondary outcomes:
measure: Pharmacokinetics: Maximum Concentration (Cmax) of LY573636
timeFrame: Predose up to 2 hours postdose in Cycles 1 and 2 (6 weeks per cycle)
measure: Number of Participants With Tumor Responses
timeFrame: Baseline to end of treatment up to 66 weeks
measure: Sunitinib Pharmacokinetics in the Presence of LY573636: Area Under the Curve (AUC)
timeFrame: Days 1 to 42 in Cycle 1 (6 weeks per cycle)
measure: Pharmacokinetics: Area Under the Curve of LY573636 Above the Albumin Corrected Threshold (AUCalb)
timeFrame: Days 1 to 42 in Cycles 1 and Cycle 2 (6 weeks per cycle)
measure: The Number of Participants With Clinically Significant Effects
timeFrame: Baseline to study completion up to 70 weeks
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: 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.
state: Indiana
city: Greenville
country: United States
facility: 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.
state: South Carolina
city: The Woodlands
country: United States
facility: 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.
state: Texas
city: Norfolk
country: United States
facility: 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.
state: Virginia
city: Montreal
country: Canada
facility: 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.
state: Quebec
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon -Fri 9AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: