Clinical Trials Register

Summary
EudraCT Number:	2013-004516-21
Sponsor's Protocol Code Number:	IMMU-107-04
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-07-22
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2013-004516-21

A.3

Full title of the trial

An International, Multi-Center, Double-Blind, Randomized, Phase III Trial of 90Y-Clivatuzumab Tetraxetan plus Low-Dose Gemcitabine Versus Placebo plus Low-Dose Gemcitabine in Patients with Metastatic (Stage IV) Pancreatic Adenocarcinoma Who Received at Least Two Prior Treatments (PANCRIT-1)

Ensayo en fase III internacional, multicéntrico, doble ciego y randomizado sobre 90Y-Clivatuzumab Tetraxetán más Gemcitabina en dosis baja en comparación con placebo más Gemcitabina en dosis baja en pacientes con adenocarcinoma pancreático metastásico (estadio IV) que hayan recibido al menos dos tratamientos con anterioridad (PANCRIT-1)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Radioimmunotherapy with 90Y-Clivatizumab Tetraxetan plus Low Dose Gemcitabine versus Placebo plus Low-Dose Gemcitabine

Radioinmunoterapia con 90Y-Clivatizumab Tetraxetán más Gemcitabina en dosis bajas en comparación con placebo más Gemcitabina en dosis bajas

A.3.2

Name or abbreviated title of the trial where available

PANCRIT-1 (PANcreatic Cancer RadioImmunoTherapy Trial 1)

A.4.1

Sponsor's protocol code number

IMMU-107-04

A.5.4

Other Identifiers

Name:

IND Number

Number:

11380

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Immunomedics, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Immunomedics, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medpace Germany GmbH
B.5.2	Functional name of contact point	Regulatoy Submissions
B.5.3	Address:
B.5.3.1	Street Address	Theresienhöhe 30
B.5.3.2	Town/ city	München
B.5.3.3	Post code	80339
B.5.3.4	Country	Germany
B.5.4	Telephone number	004989895571860
B.5.5	Fax number	+49898955718160
B.5.6	E-mail	reg.submissions@medpace.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD080/08
D.3 Description of the IMP
D.3.1	Product name	90Y-clivatuzumab tetraxetan
D.3.2	Product code	90Y-hPAM4
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	clivatizumab tetraxetan
D.3.9.1	CAS number	1462876-11-4
D.3.9.2	Current sponsor code	IMMU-107
D.3.9.3	Other descriptive name	CLIVATUZUMAB TETRAXETAN
D.3.9.4	EV Substance Code	SUB131078
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	Yes
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Metastatic (Stage IV) Pancreatic Adenocarcinoma

Adenocarcinoma pancreático metastásico (estadío IV)

E.1.1.1

Medical condition in easily understood language

Pancreatic Cancer

Cancer pancreático

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10033605
E.1.2	Term	Pancreatic cancer metastatic
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Overall Survival (OS)

supervivencia global (SG)

E.2.2

Secondary objectives of the trial

Other measurements of overall survival (OS)
Safety
Clinical benefit (KPS, Weight, FACT-HEP, Quality of Life)
Radiologic-based measure of tumor response or progression-free survival

Otras medidas de supervivencia global (SG)
Seguridad
Beneficios clínicos (KPS, peso, FACT-Hep, calidad de vida)
Medida radiológica de la respuesta del tumor o supervivencia sin progresión

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males or non-pregnant, non-lactating females ? 18 years old, able to give signed written informed consent.
2. Histologically or cytologically confirmed adenocarcinoma of the pancreas.
3. Stage IV (metastatic) disease documented by CT imaging (MRI if patient allergic to contrast media) 90Y-clivatuzumab tetraxetan
4. Received at least two prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease.
5. At least one of the prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease must have contained gemcitabine and have met the following criteria:
o Completed at least one cycle of the treatment
o Received gemcitabine administered at a minimum dose of 800 mg/m2 per
week in the first cycle of treatment
o Progressed while receiving this gemcitabine regimen or within 3 months of
completing gemcitabine
o Progression was documented,
? Preferentially radiologically by tumor growth or new lesions, or by
? Clear symptomatic deterioration supported by at least two of the
following clinical criteria: ? 10% worsening in KPS or ? 1
worsening in ECOG; increasing weakness or fatigue; progressive
weight loss; new/worsening pain requiring increased pain
medication; new/worsening jaundice, nausea, or vomiting;
new/worsening ascites or pleural effusions; other physical or
laboratory findings consistent with disease progression.
6. Adequate performance status (Karnofsky Performance Status ? 70%)
7. Expected survival ? 3 months.
8. Adequate hematology without ongoing transfusional support (hemoglobin ? 9g/dL, ANC ? 1.5 x 10^9/L, platelets ? 100 x10^9/L).
9. Adequate renal and hepatic function (creatinine and bilirubin ? 1.5 X IULN;
AST and ALT ? 2.5 X IULN [? 5.0 x IULN if due to liver metastases]).
10. At least 4 weeks beyond any major surgery or radiotherapy, 2 weeks beyond chemotherapy or other experimental treatments, and with any clinically significant related acute toxicities recovered at study entry to Grade 1 by NCI CTCAE v4.0.

1. Varones o mujeres que no estén embarazadas ni en periodo de lactancia, de ?18 años de edad, capaces de firmar un consentimiento informado por escrito.
2. Adenocarcinoma de páncreas confirmado mediante pruebas histológicas o citológicas.
3. Enfermedad en estadio IV (metastásica) documentada por TC (o RM en caso de alergia al contraste)
4. Haber recibido al menos dos pautas de tratamiento quimioterápico citotóxico sistémico para la enfermedad localmente avanzada o metastásica irresecables.
5. Al menos uno de los tratamientos quimioterápicos citotóxicos sistémicos administrados anteriormente para la enfermedad localmente avanzada o metastásica irresecables deberá haber incluido Gemcitabina y cumplir los siguientes criterios:
o Haber completado al menos un ciclo de tratamiento
o Haber recibido Gemcitabina en una dosis mínima de 800 mg/m2 por semana en el primer ciclo de tratamiento
o Haber presentado progresión durante el tratamiento con Gemcitabina o en los 3 meses siguientes a la finalización de dicho tratamiento
o Progresión documentada
6. Valoración funcional suficiente (estado funcional de Karnofsky ?70 %) (Anexo A).
7. Supervivencia prevista ?3 meses.
8. Cifras de hematología suficiente sin necesidad de transfusiones de apoyo (hemoglobina ?9 g/dl, RAN ? 1,5 ? 109/l, plaquetas ?100 ? 109/l).
9. Función renal y hepática adecuadas (creatinina y bilirrubina ?1,5 X LSNC; AST y ALT ?2,5 X LSNC [? 5,0 x LSNC si se debe a metástasis hepáticas]).
10. Deberán haber pasado más de 4 semanas desde cualquier intervención de cirugía mayor o de radioterapia y más de 2 semanas desde la quimioterapia u otros tratamientos experimentales, y el paciente deberá haberse recuperado de cualquier toxicidad aguda relacionada y clínicamente significativa que presentara a la entrada en el estudio, hasta grado ?1 según la versión 4.0 de los CTCAE del NCI.

E.4

Principal exclusion criteria

1. Patients of childbearing potential sexually active but unwilling to use ?double barrier? methods of birth control including male use of a condom with female use of a diaphragm, intrauterine device (IUD), or contraceptive sponge during the study until at least 4 weeks after the last dose of active study drug.
2. History of allergy or hypersensitivity or severe toxicity to any of the study drugs or their incipients
3. Known metastatic disease to the central nervous system, unless previously treated and well-controlled for at least 3 months [defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart]
4. Presence of bulky disease (defined as any single mass > 10 cm in greatest dimension).
5. Patients with Grade ? 3 nausea or vomiting, and/or signs of intestinal obstruction.
6. Rapid deterioration during screening prior to randomization, i.e. 10% decrease in KPS, 20% decrease in serum albumin levels, unstable pain symptoms requiring modifications in analgesic management, development of jaundice or symptomatic ascites.
Prior external beam irradiation to a field that includes more than 30% of the red
bone marrow.
8. Patients with non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, or other non-invasive malignancy are not excluded, but patients with other prior malignancies must have had at least a 2-year disease-free interval.
9. Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.
10. Patients with:
a. Active coronary artery disease, unstable angina, myocardial infarction, or congestive heart failure present within 6 months.
b. Cardiac arrhythmia (other than stable atrial fibrillation) requiring antiarrhythmia therapy, NYHA Class II-IV disease, or prolonged QT/QTc interval.
c. Other clinically significant cardiac disease, unless baseline MUGA/2DECHO performed and LVEF is within institutional limits.
11. Moderate-to-severe (Grade ? 3) respiratory illness present within 6 months.
12. Infection requiring intravenous antibiotic use within 1 week.
13. Other concurrent medical or psychiatric conditions that, in the Investigator?s
opinion, may be likely to confound study interpretation, prevent completion of
study procedures and follow-up examinations, or may cause undue risk to the patient

1. Pacientes en edad fértil y sexualmente activos que no estén dispuestos a utilizar métodos anticonceptivos de «doble barrera» como el uso de preservativo por el varón junto con diafragma, dispositivo intrauterino (DIU) o esponja anticonceptiva por la mujer, durante el estudio y hasta al menos 4 semanas después de la última administración del fármaco del estudio activo.
2. Antecedentes de alergia, hipersensibilidad o toxicidad grave a cualquier de los fármacos del estudio o de sus excipientes.
3. Metástasis en el sistema nervioso central, salvo que hayan recibido tratamiento y estén bien controladas durante al menos 3 meses [lo que se define por estabilidad clínica, ausencia de edema y de esteroides, y estabilidad en 2 imágenes obtenidas con 4 semanas de diferencia, como mínimo]
4. Presencia de tumor voluminoso (es decir, una sola masa con una dimensión máxima de >10 cm).
5. Pacientes con náuseas, vómitos o signos de obstrucciones intestinal de grado ?3.
6. Deterioro rápido durante el screening previo a la randomización, es decir, reducción ?10 % en la KPS o disminución ?20 % de la concentración sérica de albúmina, síntomas de dolor inestable que precisen modificaciones del tratamiento analgésico, aparición de ictericia o ascitis sintomática.
7. Irradiación externa previa en un campo que suponga más del 30 % de la médula ósea roja.
8. No se excluirá a los pacientes con cáncer cutáneo distinto del melanoma, carcinoma cervical in situ, cáncer superficial de vejiga u otros trastornos malignos no invasivos, pero los pacientes que hayan padecido otros trastornos malignos deberán llevar al menos 2 años sin enfermedad.
9. Pacientes seropositivos para el VIH o los virus de las hepatitis B o C.
10. Pacientes con:
a. Coronariopatía activa, angina inestable, infarto de miocardio o insuficiencia cardiaca congestiva en los 6 últimos meses.
b. Arritmia cardiaca (aparte de la fibrilación auricular estable) que precise tratamiento antiarrítmico, enfermedad de clase II a IV de la NYHA o prolongación del intervalo QT/QTc.
c. Otras cardiopatías clínicamente significativas, salvo que la MUGA/2D-ECO basal y la FEVI estén dentro de los límites del centro.
11. Enfermedad respiratoria moderada a intensa (grado ?3) en los 6 últimos meses.
12. Infección que haya precisado antibióticos por vía intravenosa en la última semana.
13. Otros trastornos médicos o psiquiátricos concurrentes que, en opinión del investigador, puedan confundir la interpretación del estudio, impedir que se lleven a cabo los procedimientos y las exploraciones de seguimiento del estudio, o causar un riesgo injustificado al paciente.

E.5 End points

E.5.1

Primary end point(s)

Overall survival (OS), which is defined as the time from the date of randomization until the date of death from any cause.

Supervivencia global (SG), deficnida como el tiempo desde la fecha de aleatorización hasta la fecha de muerte por cualquier causa

E.5.1.1

Timepoint(s) of evaluation of this end point

any time point

cualquier punto

E.5.2

Secondary end point(s)

? OS at 3, 6 and 12 months
? OS in clinically important subgroups, including Karnofsky performance status (?90% vs. <90%), extent of disease at study entry, time from initial diagnosis (<median vs. ?median), and prior therapies received (2 vs. ?2).
? Tumor response according to RECIST version 1.1, including objective response rate (the sum of complete response [CR] and partial response[PR] rates) and duration of response.
? Progression free survival (PFS).
? Clinical benefit analyses including patient weight and Karnofsky performance status.
? Quality of life analyses as assessed by the FACT-HEP questionnaire.
Safety endpoints:
? incidence and severity of adverse events,
? incidence of serious adverse events,
? safety laboratory tests (hematology and chemistry),
?vital signs,
? physical examination
? and electrocardiogram measurements.

- SG a los 3, 6 y 12 meses
- SG en subgrupos importantes desde el punto de vista clinic
- las mediciones por TC (o por RM, en caso de alergia al contraste) de la respuesta objetiva del tumor según las directrices de los Criterios de Evaluación de la Respuesta en Tumores Sólido
- la supervivencia sin progresión según los criterios RECIST1.1
- la seguridad (acontecimientos adversos, análisis y evaluaciones para determinar la seguridad)
- la relación entre beneficio clínico y calidad de vida (valoración funcional, peso y cuestionario FACT-HEP)

E.5.2.1

Timepoint(s) of evaluation of this end point

At 3, 6 and 12 months

a los 3, 6 y 12 meses

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarkers
Immunogenicity

Biomarcadores
Inmunogenicidad

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

tratamiento con Gemcitabina en baja dosis

Low dose treatment with Gemcitabine

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Israel

Spain

United States

E.8.7

Trial has a data monitoring committee

Yes

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

until 371 deaths have accrued

hasta llegar a las 371 muertes

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

440

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

140

F.4.2.2

In the whole clinical trial

440

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After discontinuation of study treatment, all patients will be followed every 4 weeks during the first year, and every 8 weeks thereafter for survival follow-up. This may be by telephone, and will include documentation of any further active therapy administrated for their pancreatic cancer.

Después de la discontinuación del tratamiento, todos los pacientes se seguirán cada 4 semanas durante el primer año y después cada 8 semanas para seguimiento de supervivencia. Será telefónicamente y podrá incluir documentación y terapia active administrada para su cancer pancreático.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-09-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-09-05

P. End of Trial
P.	End of Trial Status	Prematurely Ended

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials