| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Phase 1b: Metastatic Cancer
Phase 2: Advanced or Metastatic Unresectable Pancreatic Cancer |
Fase 1b: Cáncer metastásico
Fase 2: cáncer de páncreas no resecable metastático o avanzado |
|
| 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) |
| Cáncer (pancreático) avanzado para el que ha fallado o no existe tratamiento estándar y/o es susceptible de terapia con gemcitabine (que no pueder ser tratado con cirugía) |
|
| 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 1b:
To determine a safe/tolerable Phase 2 dose of LY2157299 for combination with gemcitabine in patients with solid malignancy, who failed previous approved therapies and/or are amenable to gemcitabine therapy (eg, pancreatic cancer, biliary tract, sarcoma).
Phase 2:
To compare overall survival (OS) in patients with Stage II-IV unresectable pancreatic cancer when treated with the combination of LY2157299 and gemcitabine with that of gemcitabine plus placebo. |
Fase 1b: Determinar una dosis segura/tolerable para la fase 2 de LY2157299 en combinación con
gemcitabina en pacientes con tumores sólidos malignos que no hayan respondido a tratamientos
aprobados previos y/o que sean candidatos a tratamiento con gemcitabina (por ejemplo, cáncer de
páncreas, vías biliares, sarcoma). Fase 2: Comparar la supervivencia global (SG) en pacientes con
cáncer de páncreas no resecable en estadio II a IV tratados con la combinación de LY2157299 y
gemcitabina y con gemcitabina más placebo. |
|
| E.2.2 | Secondary objectives of the trial |
Phase 1b:
- To assess PK profile of LY2157299 when administered together with gemcitabine
- To document any antitumor activity observed after administration of LY2157299 and gemcitabine
- To explore biomarker responses associated with LY2157299 and gemcitabine combination
Phase 2:
- To compare LY2157299 combined with gemcitabine to gemcitabine plus
placebo
- To evaluate tolerability profile of LY2157299 when administered in combination with gemcitabine
- To evaluate the PK profile of LY2157299
- To compare LY2157299 combined with gemcitabine to gemcitabine combined with placebo with regard to biomarker responses |
Fase 1b:
- Evaluar el perfil FC de LY2157299 cuando se administra junto con gemcitabina
-Documentar cualquier actividad antitumoral observada tras la administración de LY2157299 y gemcitabina
- Evaluar las respuestas de biomarcadores asociadas a la combinación de LY2157299 y gemcitabina
Fase 2:
- Comparar LY2157299 combinado con gemcitabina con gemcitabina más placebo
- Evaluar el perfil de tolerabilidad de LY2157299 administrado en combinación con gemcitabina
- Evaluar el perfil FC de LY2157299
- Comparar las repuestas de biomarcadores con LY2157299 más gemcitabina y con gemcitabina más placebo |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Ph1b: Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease; that is refractory to standard therapy and/or therapies known to provide clinical benefit or for which no standard therapy exists; and/or in which gemcitabine therapy at the proposed doses and schedule would be considered appropriate treatment for the metastatic disease (eg, pancreatic cancer)
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 1b: Patients may have received prior chemotherapy, radiotherapy, cancer-related hormone therapy, or other investigational therapy as treatment
There is no limit in the number of previous lines of therapy
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. |
Fase 1b: Presentar evidencia histológica o citológica de un diagnóstico de cáncer avanzado y/o
metastático; resistente a terapia estándar y/o tratamientos conocidos que aporten beneficios clínicos o
para el que no exista tratamiento estándar; y/o para el que, se considere adecuado el tratamiento con
gemcitabina en las dosis y la pauta propuestas para la enfermedad metastásica (por ejemplo, cáncer de
páncreas). Fase 2: Tener un diagnóstico histológico o citológico de adenocarcinoma de páncreas
localmente avanzado (estadio II, III) o metastásico (estadio IV) y no susceptible a resección con
intención curativa. Los pacientes con cirugía radical previa para el cáncer de páncreas serán elegibles
después que se documente progresión. Si han recibido quimioterapia adyuvante o quimiorradioterapia
con gemcitabina, podrán ser incluidos siempre que el tratamiento haya finalizado al menos 3 meses
antes. Fase 2: Disponibilidad de tejido tumoral o de laminillas no teñidas procedentes de la biopsia
original o resección o de otras biopsias tumorales. Tener enfermedad mensurable o no mensurable,
definida según los criterios RECIST Pacientes de ambos sexos, de 18 años de edad como mínimo.
Haber prestado el consentimiento informado antes de cualquier procedimiento específico del estudio.
Tener una función orgánica adecuada Tener un estado funcional 2 en la escala del Eastern Cooperative
Oncology Group (ECOG) En la fase 1b: Los pacientes pueden haber recibido previamente
quimioterapia, radioterapia, tratamiento hormonal relacionado con el cáncer o cualquier otro tratamiento
en investigación. No hay límite en el número de líneas de tratamiento previas. En la fase 2: Los
pacientes pueden haber recibido previamente tratamiento adyuvante con gemcitabina con o sin
radioterapia para el cáncer de páncreas. El tratamiento adyuvante debe haber terminado al menos 6
meses antes de la inclusión. Tanto en la fase 1b como en la 2, los pacientes deben haberse recuperado de
cualquier toxicidad de grado 3/4 procedente de tratamientos previos. Ser fiables y mantenerse
disponibles durante el estudio y estar dispuestos a seguir los procedimientos del mismo. Se permite la
radioterapia previa para el tratamiento del cáncer hasta <25 % de la médula ósea (Cristi y Eckermann
1987), siempre que los pacientes se hayan recuperado de los efectos tóxicos agudos del tratamiento
antes de la inclusión en el estudio. No se permite la radioterapia previa de la pelvis completa. La
radioterapia debe haber terminado al menos 4 semanas antes de la inclusión en el estudio. Los varones y
mujeres en edad fértil deben utilizar un método anticonceptivo adecuado, si procede durante el estudio y
hasta los 3 meses siguientes a la interrupción del tratamiento del mismo. |
|
| 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 or any other TGF-ß inhibitor.
Have known allergy to LY2157299 or gemcitabine or any ingredient of
LY2157299 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. |
Los pacientes serán excluidos del estudio si cumplen alguno de los siguientes criterios: Participar
actualmente, o haber discontinuado en los últimos 30 días, de un ensayo clínico con un producto en
investigación o para un uso no autorizado de un fármaco o dispositivo (diferentes del producto en
investigación utilizado en este estudio), o participar al mismo tiempo en otro tipo de investigación
médica que no se considere científica o médicamente compatible con este estudio. Tener enfermedad
cardíaca moderada o grave No poder tragar comprimidos o cápsulas. Mujeres embarazadas o en período
de lactancia. Presentar enfermedades significativas que, en opinión del investigador, no estén
adecuadamente controladas con el tratamiento apropiado o puedan comprometer la capacidad del
paciente para tolerar este tratamiento. Tener antecedentes de otro cáncer (salvo el cáncer de piel no
melanoma o el carcinoma in situ), a menos que se encuentre en remisión completa y lleven un mínimo
de 3 años sin recibir tratamiento para la enfermedad. Padecer infección activa que interfiera con los
objetivos del estudio o influya en su cumplimiento. Fase 2 solamente: tumores pancreáticos endocrinos
o cáncer ampollar. Pacientes con leucemia aguda o crónica o con otras enfermedades que puedan
presentar una infiltración significativa de la médula ósea (no se requiere ninguna selección). Haberse
retirado o haber completado previamente este estudio o cualquier otro de LY2157299 o de otro
inhibidor de TGF-β. Tener alergia conocida a LY2157299 o gemcitabina o a cualquiera de los
componentes de LY2157299 o formulaciones de gemcitabina. Formar parte del personal del centro de
investigación adscrito a este estudio y/o de sus familiares inmediatos. Se definen como familiares
inmediatos el cónyuge, progenitor, hijo o hermano, ya sea biológico o adoptado legalmente. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase 1b: to detremine a safe tolerable dose for phase 2
Phase 2: Overall survival |
Fase 1b: determinar una dosis segura/tolerable para la fase 2
Fase 2: Supervivencia global |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase 1b: 1 cycle of LY2157299 tretament (i.e 4 weeks)
Phase 2: patient death (study anticipates Phase 2 patients will be in the study @ 6 months) |
Fase 1b: 1 ciclo de tratamiento con LY2157299 (por ejemplo 4 semanas).
Fase 2: Fallecimiento del paciente (el estudio prevé que los pacientes en fase 2 permanecerán en el estudio 6 meses) |
|
| E.5.2 | Secondary end point(s) |
| define LY2157299 pharmacokinetics, investigate efficacy |
| Definifir la farmacocinética de LY2157299 e investigar su eficacia |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| PK 4weeks efficacy - 8 weeks or until pt withdraws |
| Farmacocinética, 4 semanas para la eficacia - 8 semanas o hasta que el paciente discontinúe |
|
| 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 |
| explorar la respuesta de biomarcadores asociados con LY2157299, para evaluar el perfil de tolerabilidad de LY2157299 administrado en combinación con gemcitabina |
|
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 26 |
| 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 |
|
| 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 |
Este estudio fase 1b/2 se considerará completado una vez completados todos los análisis de los datos
(incluyendo algún posible análisis de seguimiento de la supervivencia a largo plazo). En caso de cierre
del estudio y decisión de finalizar la recogida de datos, el Médico de Investigación Clínica de Lilly se
lo notificará a los investigadores |
|
| 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 |
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