A Study of LY2875358 in Patients With Advanced Cancer
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Purpose
The objective of this study is to determine a recommended Phase 2 dose range of LY2875358 that may be safely administered to patients with advanced cancer. In Part A and Part A2 of this study, escalating doses of LY2875358 as monotherapy and in combination with erlotinib will be evaluated for safety and tolerability, respectively. In Part B, LY2875358 monotherapy at maximum tolerated dose (MTD) will be explored in 5 different tumor types.
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced Cancer |
Drug: LY2875358 Drug: LY2875358 + erlotinib Drug: LY2875358 at MTD |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase 1 Study of LY2875358 in Patients With Advanced Cancer |
- Recommended dose for Phase 2 studies [ Time Frame: Baseline to study completion (3 months) ] [ Designated as safety issue: Yes ]
- Pharmacokinetics: Maximum plasma concentration (Cmax) [ Time Frame: Days 1, 2, 4, 5, 6, 8, 15, and 22 of Cycle 1. Days 1, 15, and 22 of Cycle 2. Days 1 and 15 of Cycles 3 and beyond, as well as 14 days, 29 days, and 57 days following the final treatment ] [ Designated as safety issue: No ]
- Number of patients with a tumor response [ Time Frame: Baseline to study completion (3 months) ] [ Designated as safety issue: No ]
- Pharmacokinetics: Area under the concentration-time curve (AUC) [ Time Frame: Days 1, 2, 4, 5, 6, 8, 15, and 22 of Cycle 1. Days 1, 15, and 22 of Cycle 2. Days 1 and 15 of Cycles 3 and beyond, as well as 14 days, 29 days, and 57 days following the final treatment ] [ Designated as safety issue: No ]
- Time to progression and overall survival [ Time Frame: Baseline to study completion (3 months) ] [ Designated as safety issue: No ]
- Pharmacokinetics: Area under the concentration-time curve (AUC) of erlotinib in combination with LY2875358 in Part A2 [ Time Frame: Cycle 1 ] [ Designated as safety issue: No ]
- Change from baseline in Brief Pain Inventory (BPI) in Part B: Expansion Cohort 1 [ Time Frame: Baseline, study completion (3 months) ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 95 |
| Study Start Date: | April 2010 |
| Estimated Study Completion Date: | June 2015 |
| Estimated Primary Completion Date: | December 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: LY2875358 |
Drug: LY2875358
Part A Dose escalation of LY2875358 administered intravenously (IV), Day 1 and 15 every 28 days for at least two cycles.
|
| Experimental: LY2875358 + erlotinib |
Drug: LY2875358 + erlotinib
Part A2 Dose escalation of LY2875358 administered IV, on Day 1 and 15 every 28 days for at least two cycles in combination with daily erlotinib dosing (150 mg) taken orally (PO).
|
| Experimental: LY2875358 at maximum tolerated dose (MTD) |
Drug: LY2875358 at MTD
Part B (Dose Exploration): LY2875358 at MTD administered IV, on Day 1 and 15 every 28 days for at least two cycles.
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Part A: Have histological or cytological evidence of cancer (solid tumor, lymphoma, or multiple myeloma) that is advanced and/or metastatic and an appropriate candidate for experimental therapy
- Part A2: Histologic or cytologic diagnosis of advanced Non Small Cell Lung Cancer (NSCLC), Stage IIIB with malignant pleural effusion or Stage IV, completed at least 1 prior systemic regimen, and eligible for erlotinib therapy.
- Part B: Candidate for experimental therapy after standard therapies used or non-eligible for standard therapies. Histological or cytological evidence of 1 of the 5 tumor types:
Castrate-resistant prostate cancer (CRPC) with bone metastasis:
--Progressive Disease in the setting of castrate level of testosterone
Renal Cell Carcinoma (RCC):
--Histologic diagnosis of either clear-cell or papillary RCC (metastatic and unresectable, or bilateral, multifocal, unresectable RCC localized to kidneys).
NSCLC:
--Histologic or cytologic diagnosis of advanced NSCLC, Stage IIIB with malignant pleural effusion or Stage IV
Hepatocellular Carcinoma (HCC)
--Histologic or cytologic diagnosis of hepatocellular carcinoma
- Uveal Melanoma with liver metastasis
- Part A: Have the presence of measurable or nonmeasurable disease as defined by the RECIST v1.1 (Eisenhauer et al. 2009) or Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) or have measureable disease for multiple myeloma.
- Part A2 & B (RCC, NSCLC, HCC, and uveal melanoma): Have measurable disease as defined by RECIST v1.1.
- Give written informed consent prior to any study-specific procedures.
- Adequate organ function.
- Performance status of less than or equal to 2 on ECOG scale.
- Discontinued all previous cancer therapies, and any agents that have not received regulatory approval, for at least 21 days and recovered from the acute effects of therapy. Must have discontinued mitomycin-C or nitrosourea therapy for at least 42 days.
- Reliable and available for the duration of the study and willing to follow study procedures.
- Males and females (reproductive potential): Use medically approved contraceptive precautions during the study and for 4 months following the last dose of study drug.
- Females (childbearing potential): Have had a negative serum pregnancy test before the first dose of study drug and not be breast-feeding.
- Estimated life expectancy that will permit the patient to complete 8 weeks of treatment.
Exclusion Criteria:
- Serious preexisting medical conditions
- Symptomatic central nervous system malignancy or metastasis (screening not required).
- Acute or chronic leukemia.
- Active infection including
- Have second primary malignancy that may affect the interpretation of results.
- Part A2: Unable to swallow tablets. Intolerant of therapy with erlotinib. Concomitant treatment with the cytochrome P450 3A (CYP3A) modulators. Must not have received treatment with any of these modulators within 14 days of study treatment.
- Have a history of New York Heart Association class ≥3, unstable angina, myocardial infarction 6 months prior to study drug
- QTc greater than 470 msec.
- Received previous treatment with any c-MET experimental therapeutic
Contacts and Locations| Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or | 1-317-615-4559 |
| United States, California | |
| 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. | Recruiting |
| La Jolla, California, United States, 92093 | |
| Contact: Eli Lilly | |
| 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. | Recruiting |
| Los Angeles, California, United States, 90048 | |
| Contact: Eli Lilly | |
| 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. | Recruiting |
| San Francisco, California, United States, 94115 | |
| Contact: Eli Lilly | |
| 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. | Recruiting |
| Santa Monica, California, United States, 90404 | |
| Contact: Eli Lilly | |
| United States, Florida | |
| 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. | Recruiting |
| Jacksonville, Florida, United States, 32224 | |
| Contact: Eli Lilly | |
| United States, Georgia | |
| 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. | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Eli Lilly | |
| United States, Michigan | |
| 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. | Recruiting |
| Ann Arbor, Michigan, United States, 48109 | |
| Contact: Eli Lilly | |
| United States, Minnesota | |
| 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. | Recruiting |
| Rochester, Minnesota, United States, 55902 | |
| Contact: Eli Lilly | |
| United States, Pennsylvania | |
| 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. | Recruiting |
| Philadelphia, Pennsylvania, United States, 19107 | |
| Contact: Eli Lilly | |
| 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: | NCT01287546 History of Changes |
| Other Study ID Numbers: | 13298, I4C-MC-JTBA |
| Study First Received: | January 28, 2011 |
| Last Updated: | April 19, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Neoplasms Erlotinib Protein Kinase Inhibitors |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 21, 2013