A Study of LY2875358 in Participants With Advanced Cancer

NCT01287546 | Completed Phase 1

• 2 other identifiers: 13298I4C-MC-JTBA
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 10

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.

Conditions

Advanced Cancer

Outcome Measures

Primary Outcomes (1)

• Recommended Phase 2 dose range of LY2875358 monotherapy and in combination with erlotinib

  Baseline through Cycle 1

Secondary Outcomes (6)

• 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

• Number of participants with a tumor response

  Baseline to study completion (12 months)

• 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

• Time to progression and overall survival

  Baseline to study completion (12 months)

• Pharmacokinetics: Area under the concentration-time curve (AUC) of erlotinib or trametinib in combination with LY2875358

  Cycle 1

Study Arms (4)

LY2875358

EXPERIMENTAL

Drug: LY2875358

LY2875358 + erlotinib

EXPERIMENTAL

Drug: LY2875358 + erlotinib

LY2875358 at Part A highest dose

EXPERIMENTAL

Drug: LY2875358 at Part A highest dose

LY2875358 at Part A highest dose + trametinib

EXPERIMENTAL

Drug: LY2875358 at Part A highest dose + trametinib

Interventions

LY2875358 DRUG

Part A Dose escalation of LY2875358 administered intravenously (IV), Day 1 and 15 every 28 days for at least two cycles.

LY2875358

LY2875358 + erlotinib DRUG

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).

LY2875358 + erlotinib

LY2875358 at Part A highest dose DRUG

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.

LY2875358 at Part A highest dose

LY2875358 at Part A highest dose + trametinib DRUG

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

LY2875358 at Part A highest dose + trametinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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):
• Increasing use of daily doses of opioid analgesics within 28 days prior to enrollment in the study.
• Neuroendocrine prostate cancer.
• Patients who have a solitary bone metastasis that has been irradiated are not eligible.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (10)

University of California - San Diego

La Jolla, California, 92037-0845, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048-5615, United States

Location

Univ of California San Francisco

San Francisco, California, 94115, United States

Location

UCLA

Santa Monica, California, 90404, United States

Location

Mayo Clinic of Jacksonville

Jacksonville, Florida, 32224, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-0946, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Interventions

emibetuzumab; Erlotinib Hydrochloride; trametinib

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• 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 DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2011
• First Posted: February 1, 2011
• Study Start: April 13, 2010
• Primary Completion: January 8, 2015
• Study Completion: October 26, 2016
• Last Updated: February 15, 2017

Record last verified: 2017-02

Locations

US (10)