E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Phase 2: Advanced or Metastatic Unresectable Pancreatic Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced (pancreatic) cancer that has failed standard treatment or for whom no standard treatment exists and/or is suitable for gemcitabine therapy (which cannot be treated by surgery) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase 2:
To compare overall survival (OS) in patients with Stage II-IV unresectable pancreatic cancer when treated with the combination of LY2157299 monohydrate and gemcitabine with that of gemcitabine plus placebo. |
|
E.2.2 | Secondary objectives of the trial |
Phase 2:
- To compare LY2157299 monohydrate combined with gemcitabine to gemcitabine plus
placebo
- To evaluate tolerability profile of LY2157299 monohydrate when administered in combination with gemcitabine
- To evaluate the PK profile of LY2157299 monohydrate
- To compare LY2157299 monohydrate combined with gemcitabine to gemcitabine combined with placebo with regard to biomarker responses |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Ph 2: 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.
Ph 2: 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
Ph 2: 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
Ph1b & 2: 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. |
|
E.4 | Principal 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.
Ph 2 only:
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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Phase 2: Overall survival |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase 2: patient death (study anticipates Phase 2 patients will be in the study @ 6 months) |
|
E.5.2 | Secondary end point(s) |
define LY2157299 pharmacokinetics, investigate efficacy |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK 4weeks efficacy - 8 weeks or until pt withdraws |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
explore biomarker response associated with LY2157299; to evaluate tolerability profile of LY2157299 administered in combination with gemcitabine |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
|
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
France |
Germany |
Italy |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
This Phase 1b/2 study will be considered complete following the completion of all data analyses (including any possible long-term follow-up survival analysis). The Lilly Clinical Research Physician will notify investigators in the event of study closure and the decision to stop collecting data |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |