A Study of LY2875358 in Participants With Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01287546
First received: January 28, 2011
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

The objective of this study is to determine a recommended Phase 2 dose range of LY2875358 that may be safely administered to participants 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. Part B is a dose-confirmation segment for LY2875358 therapy in 5 different types of cancer: nonsquamous non-small cell lung cancer (NSCLC), castrate resistant prostate cancer (CRPC) with bone metastases, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), or uveal melanoma with liver metastases, and for LY2875358 in combination with trametinib in participants with uveal melanoma with liver metastases.


Condition Intervention Phase
Advanced Cancer
Drug: LY2875358
Drug: LY2875358 + erlotinib
Drug: LY2875358 at Part A highest dose
Drug: LY2875358 at Part A highest dose + trametinib
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Recommended Phase 2 dose range of LY2875358 monotherapy and in combination with erlotinib [ Time Frame: Baseline through Cycle 1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 participants with a tumor response [ Time Frame: Baseline to study completion (12 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 (12 months) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Area under the concentration-time curve (AUC) of erlotinib or trametinib in combination with LY2875358 [ 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 to study completion (12 months) ] [ Designated as safety issue: No ]

Estimated Enrollment: 117
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 Part A highest dose Drug: LY2875358 at Part A highest dose
Part B (Dose Exploration): LY2875358 at Part A highest dose administered IV, on Day 1 and 15 every 28 days for at least two cycles.
Experimental: LY2875358 at Part A highest dose + trametinib Drug: LY2875358 at Part A highest dose + trametinib
Part B (in combination with trametinib): LY2875358 at Part A highest dose administered IV, on Day 1 and 15 every 28 days for at least two cycles, in combination with trametinib at 2 mg orally once daily

Detailed Description:

Protocol amendment (November, 2013) expanded Part B to study LY2875358 in combination with trametinib in participants with uveal melanoma with liver metastasis.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 participants 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 HIV, hepatitis A, B or C
  • Have second primary malignancy that may affect the interpretation of results.
  • Have received a liver transplant, or have liver cirrhosis with a Child-Pugh Stage of B or C.
  • Patients with active alcohol abuse, as determined by the treating investigator.
  • 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.
  • Part B Expansion Cohort 1 (CRPC):

    1. Increasing use of daily doses of opioid analgesics within 28 days prior to enrollment in the study.
    2. Neuroendocrine prostate cancer.
    3. Patients who have a solitary bone metastasis that has been irradiated are not eligible.
  • Part B Expansion Cohort 6 (LY2875358 plus trametinib in participants with uveal melanoma with liver metastasis): Contra-indications for trametinib
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01287546

Contacts
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Locations
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, Massachusetts
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
Boston, Massachusetts, United States, 02114
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         
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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: March 25, 2014
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 July 28, 2014