Clinical trial • Phase II • Oncology

PANITUMUMAB for Metastatic colorectal cancer | RAS and BRAF wild-type metastatic colorectal cancer

Phase II trial of PANITUMUMAB for Metastatic colorectal cancer | RAS and BRAF wild-type metastatic colorectal cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Metastatic colorectal cancer | RAS and BRAF wild-type metastatic colorectal cancer
Trial Stage
Phase II
Drug Modality
Monoclonal antibody | Small molecule

Key dates

Initial CTIS Submission Date
01-08-2024
First CTIS Authorization Date
16-09-2024

Trial design

Randomised, open-label, arm a: panitumumab followed by regorafenib. arm b: regorafenib followed by panitumumab. (arm descriptions: panitumumab until pd1, unacceptable toxicity or patient’s refusal followed after pd1 by regorafenib until pd2, unacceptable toxicity or patient’s refusal; and the reverse sequence). product information indicates panitumumab (vectibix) product with dosing units mg/kg (maxdailydoseamount 6 mg/kg) and regorafenib (stivarga) with maxdailydoseamount 160 mg, but specific per-protocol doses/schedules are not detailed in the arm descriptions.-controlled Phase II trial in Italy.

Randomised
Yes
Open Label
Yes
Comparator
Arm A: Panitumumab followed by regorafenib. Arm B: Regorafenib followed by panitumumab. (Arm descriptions: Panitumumab until PD1, unacceptable toxicity or patient’s refusal followed after PD1 by regorafenib until PD2, unacceptable toxicity or patient’s refusal; and the reverse sequence). Product information indicates panitumumab (Vectibix) product with dosing units mg/kg (maxDailyDoseAmount 6 mg/kg) and regorafenib (Stivarga) with maxDailyDoseAmount 160 mg, but specific per-protocol doses/schedules are not detailed in the arm descriptions.
Target Sample Size
214

Eligibility

Recruits 214 No vulnerable population selected; only adults (Age ≥ 18 years). Written informed consent is required (including written informed consent to molecular analyses). Subject information and informed consent forms are provided in the documentation. No assent or minor consent procedures are indicated..

Pregnancy Exclusion
Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (ofchildbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 8 weeks after the last trial treatment.
Vulnerable Population
No vulnerable population selected; only adults (Age ≥ 18 years). Written informed consent is required (including written informed consent to molecular analyses). Subject information and informed consent forms are provided in the documentation. No assent or minor consent procedures are indicated.

Inclusion criteria

  • {"criterion_text":"- Age ≥ 18 years\n- Written informed consent to molecular analyses.\n- Histologically proven diagnosis of CRC\n- At least one measurable lesion according to RECIST1.1\n- ECOG PS ≤ 1.\n- mCRC previously treated for metastatic disease with, or not considered candidates for, fluoropyrimidine, oxaliplatin, irinotecan and anti-angiogenic monoclonal antibody (bevacizumab or aflibercept);\n- RAS (codons 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes) and BRAF (V600E mutation) wt status of primary CRC or related metastasis (local laboratory assessment).\n- Previous first-line anti-EGFR-containing therapy producing at least a partial response or a stable disease ≥ 6 months;\n- At least 4 months elapsed between the end of first-line anti-EGFR administration and screening;\n- At least one line of therapy between the end of first-line anti-EGFR administration and screening;\n- Availability of plasma sample for liquid biopsy within 28 days prior enrolment\n- RAS (codons 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes) and BRAF (V600E mutation) wt status of ct-DNA at screening (central laboratory assessment by means of IdyllaTM ctKRAS-NRAS-BRAF Mutation Test, Biocartis, Inc.).\n- Written informed consent to study procedures\n- Life expectancy of at least 12 weeks\n- Availability of archival tumour tissue (primary tumour and metastases or at least one of the two) for biomarker analysis;\n- Availability of biological samples for translational molecular analyses\n- Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl.\n- Total bilirubin ≤ 1.5 fold the upper-normal limits (UNL), ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or <5 x UNL in the case of liver metastases), alkaline phosphatase ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases).\n- Creatinine clearance ≥ 50 mL/min or serum creatinine ≤1.5 x UNL.\n- Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient\n- Subjects and their partners must be willing to avoid pregnancy during the trial and until 8 weeks after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception)\n- Will and ability to comply with the protocol."}

Exclusion criteria

  • {"criterion_text":"- Previous treatment with regorafenib.\n- Radiotherapy to any site within 4 weeks before the study.\n- Untreated brain metastases or spinal cord compression or primary brain tumours\n- Evidence of bleeding diathesis or coagulopathy\n- Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.\n- Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.\n- Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment\n- Any previous venous thromboembolism ≥ NCI CTCAE Grade 4.\n- History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment\n- Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ\n- Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication\n- Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs.\n- Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies\n- Diagnosis of interstitial pneumonitis or pulmonary fibrosis.\n- Active uncontrolled infections or other clinically relevant concomitant illness contraindicating administration of panitumumab and regorafenib\n- Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer).\n- Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (ofchildbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 8 weeks after the last trial treatment."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary endpoint is Overall Survival. OS is defined as the time from randomization to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive","definition_or_measurement_approach":"OS is defined as the time from randomization to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive"}

Secondary endpoints

  • {"endpoint_text":"- Overall Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during panitumumab and regorafenib\n- G3/4 Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during panitumumab and regorafenib.\n- 1st-Progression free survival (1st-PFS) is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first.\n- 2nd-Progression free survival (2nd-PFS) is defined as the time from the beginning of the second-line study treatment to the documentation of objective disease progression according to RECIST 1.1 criteria or death due to any cause, whichever occurs first.\n- Time to Failure of strategy (TFS) is defined as the time from randomization till the first of any of the following events: a) death; b) disease progression according to RECIST 1.1 criteria on any treatment given after 1st progression. For patients that will not receive any treatment within 3 months after 1st progression, TFS will be equal to PFS.\n- Objective Response Rate (ORR) is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, during panitumumab and regorafenib. The determination of clinical response will be based on investigator reported measurements. Responses will be evaluated every 8 weeks","definition_or_measurement_approach":"Overall Toxicity Rate: percentage of patients experiencing any adverse event per NCI CTCAE v5.0 during treatments. G3/4 Toxicity Rate: percentage experiencing grade 3/4 events per NCI CTCAE v5.0 during treatments. 1st-PFS: time from randomization to first objective progression or death. 2nd-PFS: time from start of second-line study treatment to progression per RECIST 1.1 or death. TFS: time from randomization to death or progression on any post-1st-progression treatment (or equal to PFS if no treatment within 3 months). ORR: percentage achieving CR or PR per RECIST 1.1 based on investigator-reported measurements, assessed every 8 weeks."}

Recruitment

Planned Sample Size
214
Recruitment Window Months
55
Consent Approach
Written informed consent is required from participants for study procedures and for molecular analyses. Subject information and informed consent forms are provided (documents L1_Main ICF_Redatto and related ICF documents). Participants are adults (Age ≥ 18 years); no assent or minor-consent procedures are specified. Languages of forms not specified in available records.

Geography

Total Number Of Sites
50
Total Number Of Participants
214

Italy

Earliest CTIS Part Ii Submission Date
09-08-2024
Latest Decision Or Authorization Date
16-09-2024
Processing Time Days
38
Number Of Sites
50
Number Of Participants
214

Sites

Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
Oncologia Medica
Contact Person Name
Michele Ghidini
Site Name
Azienda USL Toscana Centro
Department Name
Oncologia Medica
Contact Person Name
Samantha Di Donato
Site Name
Ospedale San Raffaele S.r.l.
Department Name
DIPARTIMENTO DI ONCOLOGIA MEDICA
Contact Person Name
Monica Ronzoni
Contact Person Email
ronzoni.monica@hsr.it
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
SSD Colo-Rectal Cancer Unit
Contact Person Name
Patrizia Racca
Contact Person Email
pracca@cittadellasalute.to.it
Site Name
Azienda Sanitaria Universitaria Friuli Centrale
Department Name
Dipartimento di Attività integrata di Oncologia
Contact Person Name
Nicoletta Pella
Site Name
Azienda Unita' Sanitaria Locale Toscana Sud Est
Department Name
UOC Oncologia Medica
Contact Person Name
Gemma Zucchelli
Site Name
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Department Name
SCDU Oncologia
Contact Person Name
Alessandra Gennari
Contact Person Email
alessandra.gennari@uniupo.it
Site Name
Centro Di Riferimento Oncologico Di Aviano
Department Name
SOC Oncologia Medica e Prevenzione Oncologica
Contact Person Name
Angela Buonadonna
Contact Person Email
abuonadonna@cro.it
Site Name
Azienda Sociosanitaria Ligure 2
Department Name
S.C.oncologia
Contact Person Name
Claudia Sonaglio
Contact Person Email
oncologia.sv@asl2.liguria.it
Site Name
Azienda Ospedaliera Papardo
Department Name
UOC Oncologia medica 1
Contact Person Name
Rosa Berenato
Contact Person Email
rosyberenato@hotmail.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
U.O.C. Oncologia Medica 1
Contact Person Name
Alberto Sobrero
Contact Person Email
alberto.sobrero@hsanmartino.it
Site Name
Careggi University Hospital
Department Name
Oncologia Medica
Contact Person Name
Lorenzo Antonuzzo
Site Name
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
DIPARTIMENTO DI MEDICINA DI PRECISIONE
Contact Person Name
Fortunato Ciardiello
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Oncologia Medica 1
Contact Person Name
Filippo Pietrantonio
Site Name
Fondazione Poliambulanza
Department Name
U.O. ONCOLOGIA MEDICA
Contact Person Name
Michela Libertini
Site Name
Istituto Oncologico Veneto
Department Name
Oncologia Medica 1
Contact Person Name
Sara Lonardi
Contact Person Email
sara.lonardi@iov.veneto.it
Site Name
Azienda Sanitaria Locale Roma 2
Department Name
DH Oncologia
Contact Person Name
Teresa Gamucci
Contact Person Email
teresa.gamucci@aslroma2.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
U.O. Clinica di Medicina Interna a indirizzo Oncologico
Contact Person Name
Alberto Ballestrero
Contact Person Email
aballestrero@unige.it
Site Name
Ospedale Fabrizio Spaziani
Department Name
UO Oncologia Medica
Contact Person Name
Roberta Grande
Contact Person Email
robertagrande@virgilio.it
Site Name
Azienda Ospedaliera Policlinico Universitario Tor Vergata
Department Name
DIPARTIMENTO DI ONCOEMATOLOGIA
Contact Person Name
Vincenzo Formica
Contact Person Email
frmvcn01@uniroma2.it
Site Name
Ente Ospedaliero Ospedali Galliera Di Genova
Department Name
S.C. Oncologia Medica
Contact Person Name
Matteo Clavarezza
Contact Person Email
matteo.clavarezza@galliera.it
Site Name
Ospedale Isola Tiberina Gemelli Isola
Department Name
U.O. Oncologia
Contact Person Name
Domenico Cristiano Corsi
Site Name
Azienda Sanitaria Locale Br
Department Name
U.O.C. Oncologia Medica
Contact Person Name
Saverio Cinieri
Contact Person Email
saverio.cinieri@icloud.com
Site Name
Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon
Department Name
Oncologia Medica
Contact Person Name
Daniele Santini
Contact Person Email
d.santini@unicampus.it
Site Name
I.F.O. Istituti Fisioterapici Ospitalieri
Department Name
Oncologia Medica
Contact Person Name
Emanuela Dell'Aquila
Contact Person Email
emanuela.dellaquila@ifo.it
Site Name
Azienda Ospedaliera Santa Croce E Carle
Department Name
Dip. Area Medica
Contact Person Name
Elena Fea
Contact Person Email
fea.e@ospedale.cuneo.it
Site Name
Azienda Sanitaria Locale Citta Di Torino
Department Name
S.C. Oncologia
Contact Person Name
Cristiano Oliva
Contact Person Email
cristiano.oliva@gmail.com
Site Name
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
Department Name
U.O.C Oncologia Medica
Contact Person Name
Laura Noto
Contact Person Email
lauranoto1983@hotmail.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Oncologia Medica
Contact Person Name
Giampaolo Tortora
Site Name
Azienda Ospedaliero Universitaria Delle Marche
Department Name
Oncologia Medica
Contact Person Name
Rossana Berardi
Site Name
Azienda Unita' Sanitaria Locale Toscana Nord Ovest
Department Name
SC Oncologia
Contact Person Name
Editta Baldini
Site Name
Azienda Unita Locale Socio Sanitaria N 8 Berica
Department Name
Dipartimento di Oncologia
Contact Person Name
Francesca Simionato
Site Name
Azienda Ospedaliera Ospedali Riuniti Marche Nord
Department Name
Oncologia
Contact Person Name
Rita Chiari
Site Name
Azienda Ospedaliero-Universitaria Di Cagliari
Department Name
SC Oncologia Medica
Contact Person Name
Mario Scartozzi
Contact Person Email
marioscartozzi@gmail.com
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
U.O. Oncologia Medica 2 Universitaria
Contact Person Name
Roberto Moretto
Contact Person Email
robertomoretto8468@gmail.com
Site Name
Azienda Sanitaria Locale Della Provincia Di Biella
Department Name
S.C. Oncologia
Contact Person Name
Myriam Paris
Contact Person Email
myriam.paris@aslbi.piemonte.it
Site Name
Azienda Unita' Sanitaria Locale Toscana Nord Ovest
Department Name
UOC Oncologia Medica
Contact Person Name
Giacomo Allegrini
Site Name
Azienda Provinciale Per I Servizi Sanitari
Department Name
Oncologia Medica
Contact Person Name
Michela Frisighelli
Contact Person Email
michela.frisighelli@apss.tn.it
Site Name
Azienda Unita' Sanitaria Locale Toscana Sud Est
Department Name
Oncologia
Contact Person Name
Carlo Milandri
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
Dipartimento di Oncologia AUSL della Romagna
Contact Person Name
Stefano Tamberi
Contact Person Email
ste.tamberi@gmail.com
Site Name
Azienda Sanitaria Locale Viterbo
Department Name
U.O. Oncologia
Contact Person Name
Mario Giovanni Chilelli
Contact Person Email
mgchilelli@libero.it
Site Name
Ospedale A. Murri ASUR Marche AV4 Fermo
Department Name
UOC Oncologia
Contact Person Name
Renato Bisonni
Site Name
Pia Fondazione Di Culto E Religione Card G Panico
Department Name
UOC Oncologia
Contact Person Name
Emiliano Tamburini
Contact Person Email
emilianotamburini@icloud.com
Site Name
Azienda Ospedaliera Ordine Mauriziano Di Torino
Department Name
Oncologia
Contact Person Name
Elisa Sperti
Contact Person Email
esperti@mauriziano.it
Site Name
Azienda USL IRCCS Di Reggio Emilia
Department Name
S.C. Oncologia Medica
Contact Person Name
Maria Banzi
Contact Person Email
maria.banzi@ausl.re.it
Site Name
Azienda Unita' Sanitaria Locale Toscana Sud Est
Department Name
U.O.C. Oncologia Medica
Contact Person Name
Angelo Martignetti
Site Name
Istituto Di Candiolo Fondazione Del Piemonte Per L'Oncologia IRCCS
Department Name
Oncologia Medica
Contact Person Name
Elisabetta Fenocchio
Contact Person Email
elisabetta.fenocchio@ircc.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Oncologia Medica
Contact Person Name
Alessandro Passardi
Site Name
Casa Sollievo Della Sofferenza
Department Name
Oncologia
Contact Person Name
Tiziana Pia Latiano
Contact Person Email
latianotiziana@gmail.com
Site Name
University Hospital Consorziale Policlinico
Department Name
U.O. Oncologia Medica Universitaria
Contact Person Name
Francesco Mannavola
Contact Person Email
francesco.mannavola@gmail.com

Sponsor

Primary sponsor

Full Name
Gruppo Oncologico Del Nord Ovest
Organisation Type
Patient organisation/association
Country Of Registered Address
Italy

Third parties

  • {"country":"Italy","full_name":"Fondazione IRCCS Istituto Nazionale Dei Tumori","duties_or_roles":"Screen molec stato RAS (cod 12 13 59 61 117 146 geni KRAS NRAS BRAF mut V600E wt DNA tumor circ","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Italy","full_name":"DataRiver","duties_or_roles":"code: 7","organisation_type":"SME"}
  • {"country":"Italy","full_name":"Azienda Ospedaliero Universitaria Pisana","duties_or_roles":"storage of biological samples, exploratory analysis of biomarkers responsible for possible mechanisms of resistance,X-ray image storage and review","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Italy","full_name":"Opis S.r.l.","duties_or_roles":"code: 12","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Vectibix 20 mg/ml concentrate for solution for infusion
Active Substance
PANITUMUMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous use
Route
Intravenous
Authorisation Status
Authorised in EU (Marketing Authorisation EU/1/07/423/001)
Maximum Dose
6 mg/kg (maxDailyDoseAmount 6 mg/kg; maxTotalDoseAmount 216)
Investigational Product Name
Stivarga 40 mg film-coated tablets
Active Substance
REGORAFENIB
Modality
Small molecule
Routes Of Administration
Oral use
Route
Oral
Authorisation Status
Authorised in EU (Marketing Authorisation EU/1/13/858/001)
Maximum Dose
160 mg (maxDailyDoseAmount 160 mg)

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