This is an open-label, multicenter, nonrandomized Phase 1b study of oral administration of LY2157299 in combination with gemcitabine followed by a randomized, double-blind, Phase 2 study of oral administration of LY2157299 monohydrate in combination with gemcitabine versus gemcitabine plus placebo

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2011-000211-64-IT
• Date of registration: 09/08/2012
• Prospective Registration: Yes
• Primary sponsor: ELI LILLY AND COMPANY
• Public title: This is an open-label, multicenter, nonrandomized Phase 1b study of oral administration of LY2157299 in combination with gemcitabine followed by a randomized, double-blind, Phase 2 study of oral administration of LY2157299 monohydrate in combination with gemcitabine versus gemcitabine plus placebo
• Scientific title: A Phase 1b/2 Study with Gemcitabine and LY2157299 for Patients with Metastatic Cancer (Phase 1b) and Advanced or Metastatic Unresectable Pancreatic Cancer (Phase 2)
• Date of first enrolment: 16/08/2012
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000211-64
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Germany, Italy, Spain, United States

Contacts

• Name: Clinical Trial Information
• Affiliation: Eli Lilly and Company

• Name: Clinical Trial Information
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion criteria

Inclusion criteria:
Have histological or cytological diagnosis of adenocarcinoma of the
pancreas that is locally advanced (Stage II, III) or metastatic (Stage IV)and not amenable to resection with curative intent. Patients with
previous radical surgery for pancreatic cancer are eligible after
progression is documented. If they received adjuvant chemotherapy or
chemoradiotherapy with gemcitabine, they can be enrolled if the
treatment was completed 3 months before or longer.
-Tumor tissue or unstained slides are available from original biopsy
or resection or other tumor biopsies.
Have measurable disease or non-measurable disease, defined according
to RECIST
- Males or females at least 18 years of age.
- Have given written informed consent prior to any study-specific procedures
- Have adequate organ function
- Have a performance status of =2 on the Eastern Cooperative Oncology
Group
-Patients may have received previous adjuvant treatment with gemcitabine with or without radiotherapy for pancreatic cancer
Adjuvant treatment must have finished at least 6 months before enrolling
- patients must have recovered from any Grade 3/4 toxicities of previous therapies
Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
Prior radiation therapy for treatment of cancer is allowed to <25% of the
bone marrow (Cristy and Eckerman 1987), and patients must have
recovered from the acute toxic effects of their treatment prior to study
enrollment. Prior radiation to the whole pelvis is not allowed. Prior
radiotherapy must be completed at least 4 weeks before study entry.
Male and female patients with reproductive potential must use an
approved contraceptive method, if appropriate, during and for 3 months
after discontinuation of study treatment.
Women of childbearing potential must have a negative beta-human
chorionic gonadotropin pregnancy test documented within 14 days prior
to treatment. If condoms are used as a barrier contraceptive, a
spermicidal agent should be added to ensure that pregnancy does not
occur. Should a woman become pregnant or suspect she is pregnant
while participating in this study, she should inform her treating
physician immediately.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion criteria:
Patients will be excluded from the study if they meet any of the
following criteria:
Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research
judged not to be scientifically or medically compatible with this study.
Have moderate or severe cardiac disease
Are unable to swallow tablets or capsules.
Are pregnant or breastfeeding.
Have any significant medical illnesses that, in the investigator's opinion,
cannot be adequately controlled with appropriate therapy or would
compromise the patient?s ability to tolerate this therapy.
Have a history of any other cancer (except non-melanoma skin cancer or
carcinoma in-situ), unless in complete remission and off of all therapy
for that disease for a minimum of 3 years.
Have active infection that would interfere with the study objectives or
influence study compliance.
Endocrine pancreatic tumors or ampullary cancer.
Patients with acute or chronic leukemia or with any other disease likely to have a significant bone marrow infiltration (screening not required).
Have previously completed or withdrawn from this study or any other
study investigating LY2157299 monohydrate or any other TGF-ß
inhibitor.
Have known allergy to LY2157299 monohydrate or gemcitabine or any
ingredient of LY2157299 monohydrate or gemcitabine formulations.
Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse,parent, child, or sibling, whether biological or legally adopted.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced or Metastatic Unresectable Pancreatic Cancer
MedDRA version: 14.1 Level: LLT Classification code 10033606 Term: Pancreatic cancer non-resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: LY2157299 monohydrate
Product Code: LY2157299
Pharmaceutical Form: Coated tablet
INN or Proposed INN: LY2157299 monohydrate
CAS Number: 924898-09-9
Current Sponsor code: LY2157299
Other descriptive name: LY2157299 monohydrate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
INN or Proposed INN: LY2157299 monohydrate
CAS Number: 924898-09-9
Current Sponsor code: LY2157299
Other descriptive name: LY2157299 monohydrate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Gemzar 1000 mg
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE HYDROCHLORIDE
CAS Number: 122111-03-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Primary Outcome(s)

Primary end point(s): Overall survival

Main Objective: To compare the overall survival (OS) of patients with Stage II to IV
unresectable pancreatic cancer when treated with a combination of LY2157299 monohydrate and gemcitabine with that of gemcitabine plus placebo.

Secondary Objective: - To compare LY2157299 monohydrate combined with gemcitabine to gemcitabine plus placebo;
- To evaluate tolerability profile of LY2157299 monhydrate when administered in combination with gemcitabine
• To evaluate the PK profile of LY2157299 monohydrate
• To compare of LY2157299 monohydrate plus gemcitabine to gemcitabine plus placebo with regard to biomarker responses.
PLEASE REFER TO THE PROTOCOL FOR FULL DESCRIPTION OF SECONDARY OBJECTIVES OF THE TRIAL

Timepoint(s) of evaluation of this end point: patient death (study anticipates Phase 2 patients will be in the
study @ 6 months)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: PK 4weeks efficacy - 8 weeks or until pt withdraws

Secondary end point(s): define LY2157299 monohydrate pharmacokinetics, investigate efficacy

Secondary ID(s)

H9H-MC-JBAJ

2011-000211-64-ES

Source(s) of Monetary Support

Eli Lilly and Company