Clinical Trials Register

Summary
EudraCT Number:	2016-001259-34
Sponsor's Protocol Code Number:	FoRT01/2016
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-07
Trial 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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-001259-34

A.3

Full title of the trial

PF-06463922 for crizotinib pretreated ROS1 positive non-small-cell lung cancer: a phase II Trial (PFROST)

PF-06463922 nel tumore al polmone non a piccole cellule con traslocazione ROS1 pretrattato con Crizotinib: uno studio di fase II (PFROST)

A.3.1

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

PF-06463922 for crizotinib pretreated ROS1 positive non-small-cell lung cancer: a phase II Trial (PFROST)

PF-06463922 nel tumore al polmone non a piccole cellule con traslocazione ROS1 pretrattato con Crizotinib: uno studio di fase II (PFROST)

A.3.2

Name or abbreviated title of the trial where available

PFROST

A.4.1

Sponsor's protocol code number

FoRT01/2016

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	FONDAZIONE RICERCA TRASLAZIONALE (FORT)
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Pfizer Italia
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fondazione Ricerca Traslazionale (FoRT)
B.5.2	Functional name of contact point	Servizio Informazione sulla Sperime
B.5.3	Address:
B.5.3.1	Street Address	Via Magnagrecia 30/a
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00183
B.5.3.4	Country	Italy
B.5.4	Telephone number	0544285206
B.5.5	Fax number	0544285206
B.5.6	E-mail	f.cappuzzo@googlemail.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PF-06463922
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PF-06463922
D.3.9.2	Current sponsor code	PF-06463922
D.3.9.4	EV Substance Code	SUB12819
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	No
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	No
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

ROS1 positive non-small-cell lung cancer

tumore al polmone non a piccole cellule con traslocazione ROS1

E.1.1.1

Medical condition in easily understood language

ROS1 positive non-small-cell lung cancer

tumore al polmone non a piccole cellule con traslocazione ROS1

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10061873
E.1.2	Term	Non-small cell lung cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10061873
E.1.2	Term	Non-small cell lung cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy and safety and tolerability of PF-06463922 in crizotinib-pre-treated metastatic non-small-cell lung cancer with ROS1 translocation.

Valutare l¿efficacia, la sicurezza e la tollerabilit¿ del PF-06463922 nel tumore metastatico al polmone non a piccole cellule con traslocazione ROS1 pretattato con Crizotinib.

E.2.2

Secondary objectives of the trial

To evaluate the progression-free survival (PFS), Overall Survival and Toxicity

Valutare la sopravvivenza libera da progressione (PFS), la sopravvivenza globale (OS) e le eventuali tossicit¿ in pazienti trattati con PF-06463922

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Other types of substudies
Specify title, date and version of each substudy with relative objectives: Version 1.0 , 5 April 2016. Tumor specimens collected at the time or after crizotinib failure will be analysed for ROS1 status (translocation and mutations). Additional biomarkers could be investigated if considered relevant by the Principal Investigator.
For each patient enrolled in the study a blood sample (12 mL) will be collected at study enrolment and at disease progression.
Changes in biomarkers expression from screening/baseline to disease progression will be analyzed.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: v1.0 del 5 aprile 2016. I campioni tumorali raccolti in contemporanea al trattamento o dopo il fallimento del crizotinib saranno analizzati per valutare lo status di ROS1 (traslocazioni e mutazioni). Potrebbero essere valutati Biomarkers addizionali se considerati rilevanti dal Principal Investigator.
1.1 Per ogni paziente arruolato nello studio sar¿ raccolto un campione di sangue (12 mL) al momento dell¿arruolamento e a progressione della malattia. Saranno analizzati i cambiamenti dell¿espressione di biomarkers tra lo screening/ basale e la progressione della malattia.

E.3

Principal inclusion criteria

1. Written informed consent;
2. Male or female patient ages = 18 years;
3. Histologically/cytologically confirmed diagnosis of NSCLC with evidence of ROS1 rearrangement;
4. Possibility to perform a new tumor biopsy or tumor tissue collected at the time or after crizotinib failure;
5. Patient pretreated with crizotinib with evidence of disease progression during crizotinib therapy;
6. At least one radiological measurable disease according to RECIST criteria;
7. At least 1 previous standard chemotherapy regimen;
8. Performance status 0-2 (ECOG);
9. Patient compliance to trial procedures
10. Adequate bone marrow function (ANC = 1.5x109/L, platelets = 100x109/L, haemoglobin > 9 g/dl);
11. Adequate liver function (bilirubin < grade 2, transaminases no more than 3xULN/<5xULN in present of liver metastases);
12. Normal level of alkaline phosphatase and creatinine;
13. If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of approved contraceptive method [intrauterine contraceptive device (IUD), birth control pills, or barrier device] during and for ninety (90) days after end of treatment.

1. Consenso informato scritto;
2. Uomini o donne con età = 18 anni;
3. Diagnosi di NSCLC confermata istologicamente/citologicamente con evidenza di riarrangiamento ROS1;
4. Possibilità di effettuare una nuova biopsia tumorale o collezionare tessuto tumorale durante o dopo il fallimento terapeutico del Crizotinib;
5. Paziente pretattato con Crizotinib con evidenza di progressione della malattia durante la terapia con il Crizotinib;
6. Almeno una lesione misurabile radiologicamente in accordo ai criteri RECIST;
7. Almeno 1 regime precedente di chemioterapia standard;
8. Performance status 0-2 (ECOG);
9. Compliance del paziente alle procedure cliniche;
10. Adeguata funzionalità del midollo osseo (ANC = 1,5x109 / L, piastrine = 100x109 / L, emoglobina> 9 g / dl);
11. Adeguata funzionalità epatica (bilirubina <grado 2, transaminasi non più di 3 ULN / <5 ULN in presenza di metastasi epatiche);
12. Livelli normali di fosfatasi alcalina e creatinina;
13. Per le donne in età fertile, è richiesto l’utilizzo di metodo contraccettivo approvato [dispositivo contraccettivo intrauterino (IUD), pillole anticoncezionali, o dispositivo barriera] durante e per novanta (90) giorni dopo fine del trattamento, altrimenti è richiesta documentazione attestante lo stato menopausale o l’impossibilità di procreare come conseguenza di intervento chirurgico o radioterapia

E.4

Principal exclusion criteria

1. No ROS1 rearrangement
2. No previous therapy with crizotinib;
3. No evidence of crizotinib failure;
4. No post-crizotinib tumor tissue available;
5. Absence of any measurable lesions;
6. No previous chemotherapy;
7. Concomitant radiotherapy or chemotherapy;
8. Symptomatic brain metastases;
9. Diagnosis of any other malignancy during the last 5 years, except for in situ carcinoma of cervix uteri and squamous cell carcinoma of the skin;
10. Predisposing factors for acute pancreatitis (e.g., uncontrolled hyperglycaemia, current gallstone disease, alcoholism);
11. History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersentivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis (but not history of prior radiation pneumonitis);
12. Pregnancy or lactating female;
13. Other serious illness or medical condition potentially interfering with the study.

1. Assenza di riarrangiamento ROS 1;
2. Nessuna precedente terapia con Crizotinib;
3. Nessuna evidenza di progressione durante il trattamento con Crizotinib
4. Nessuna disponibilità di tessuto tumorale dopo il trattamento con Crizotinib
5. Assenza di qualsiasi lesione misurabile;
6. Nessuna chemioterapia precedente;
7. Radioterapia o chemioterapia concomitante;
8. Metastasi cerebrali sintomatiche;
9. Diagnosi di qualsiasi altro tumore maligno durante gli ultimi cinque anni, eccetto per il carcinoma in situ della cervice uterina e per il carcinoma della pelle a cellule squamose
10. Predisposizione per una pancreatite acuta (ad esempio , iperglicemia incontrollata , colelitiasi corrente , alcolismo)
11. Storia di vasta diffusione / bilaterale o presenza nota di fibrosi interstiziale di grado 3 o 4 o malattia polmonare interstiziale inclusa storia di polmonite, polmonite da ipersensibilità, polmonite interstiziale, malattia polmonare interstiziale, bronchiolite obliterante e fibrosi polmonare (ma non storia di precedente polmonite conseguente a radioterapia);
12. Gravidanza o allattamento
13. Altre grave malattia o condizione medica che potrebbe potenzialmente interferire con lo studio.

E.5 End points

E.5.1

Primary end point(s)

Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib

Tasso di risposta al PF-06463922 in pazienti con traslocazione ROS1 resistenti al crizotinib

E.5.1.1

Timepoint(s) of evaluation of this end point

24 month

24 mesi

E.5.2

Secondary end point(s)

¿ Progression-free survival (PFS)
¿ Overall Survival (OS)
¿ Toxicity
¿ Correlation with additional tumor biomarkers in tumor tissue or blood

¿ Sopravvivenza libera da progressione (PFS)
¿ Sopravvivenza globale (OS)
¿ Tossicit¿
¿ Correlazione con biomarkers tumorali addizionali in tessuti tumorali o nel sangue

E.5.2.1

Timepoint(s) of evaluation of this end point

Eligible patients will be treated with the study drug until disease progression, unacceptable toxicity or patient refusal.

I pazienti eleggibili saranno trattati con il farmaco in studio fino a progressione della malattia, inaccettabile tossicit¿ o rifiuto del paziente stesso e monitorati successivamente per la OS

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

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

E.8.2.3

Other

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

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

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

Study treatment will continue until one of the following conditions apply - whichever comes first:
¿ tumor progression
¿ unacceptable toxicity according to investigator¿s judgment
¿ death
¿ discontinuation from the study for any other reason

Il trattamento di studio sar¿ continuativo fino a che una delle seguenti condizioni si verifichi:
¿Progressione di malattia
¿Tossicit¿ inaccettabile a giudizio dello sperimentatore
¿Decesso
¿Uscita dallo studio per altri motivi

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:

F.1.3

Elderly (>=65 years)

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Subjects unable to dare the Consent for Physical Reasons

Soggetti incapaci di dare il consenso per motivi fisici

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

F.4.2.2

In the whole clinical trial

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)

Not applicable

Non applicabile

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

2016-07-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-08-31

P. End of Trial
P.	End of Trial Status	Ongoing

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