Clincosm LogoSign in Get a demo

A Study of LY2875358 in Participants With Advanced Cancer

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01287546
Collaborator
(none)
117
Enrollment
10
Locations
4
Arms
78.5
Actual Duration (Months)
11.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
  • Drug: LY2875358
  • Drug: LY2875358 + erlotinib
  • Drug: LY2875358 at Part A highest dose
  • Drug: LY2875358 at Part A highest dose + trametinib
 Phase 1

Detailed Description

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

Study Design

Study Type:
Interventional
Anticipated Enrollment :
117 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study of LY2875358 in Patients With Advanced Cancer
Actual Study Start Date :
Apr 13, 2010
Actual Primary Completion Date :
Jan 8, 2015
Actual Study Completion Date :
Oct 26, 2016

Arms and Interventions

Arm Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

  1. Recommended Phase 2 dose range of LY2875358 monotherapy and in combination with erlotinib [Baseline through Cycle 1]

Secondary Outcome Measures

  1. Pharmacokinetics: Maximum plasma concentration (Cmax) [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]

  2. Number of participants with a tumor response [Baseline to study completion (12 months)]

  3. Pharmacokinetics: Area under the concentration-time curve (AUC) [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]

  4. Time to progression and overall survival [Baseline to study completion (12 months)]

  5. Pharmacokinetics: Area under the concentration-time curve (AUC) of erlotinib or trametinib in combination with LY2875358 [Cycle 1]

  6. Change from baseline in Brief Pain Inventory (BPI) in Part B: Expansion Cohort 1 [Baseline to study completion (12 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
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 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

Locations

Site City State Country Postal Code
1 University of California - San Diego La Jolla California United States 92037-0845
2 Cedars Sinai Medical Center Los Angeles California United States 90048-5615
3 Univ of California San Francisco San Francisco California United States 94115
4 UCLA Santa Monica California United States 90404
5 Mayo Clinic of Jacksonville Jacksonville Florida United States 32224
6 Emory University Atlanta Georgia United States 30322
7 Massachusetts General Hospital Boston Massachusetts United States 02114
8 University of Michigan Ann Arbor Michigan United States 48109-0946
9 Mayo Clinic Rochester Minnesota United States 55902
10 Thomas Jefferson University Philadelphia Pennsylvania United States 19107

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01287546
Other Study ID Numbers:
  • 13298
  • I4C-MC-JTBA
First Posted:
Feb 1, 2011
Last Update Posted:
Feb 15, 2017
Last Verified:
Feb 1, 2017
Additional relevant MeSH terms:
Neoplasms
Erlotinib Hydrochloride
Trametinib

Study Results

No Results Posted as of Feb 15, 2017