Clinical trial • Phase I/II • Oncology

CAPECITABINE for Breast cancer | Metastatic breast cancer

Phase I/II trial of CAPECITABINE for Breast cancer | Metastatic breast cancer. Randomised, open-label, adaptive. 44 participants.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Breast cancer | Metastatic breast cancer
Trial Stage
Phase I/II
Drug Modality
Radiopharmaceutical | Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
13-12-2023
First CTIS Authorization Date
23-04-2024

Trial design

Randomised, open-label, adaptive Phase I/II trial in Italy, Germany, Spain and others.

Randomised
Yes
Open Label
Yes
Adaptive
True - Phase I includes dose-escalation to determine Recommended Doses (RD) and dosing regimens; Phase II evaluates preliminary anti-tumor activity across two randomized cohorts of two different doses/regimens to optimize dosing. Specific escalation rules and stopping rules not provided in CTIS summary.
Biomarker Stratified
True, biomarker: GRPR status assessed by [68Ga]Ga-NeoB PET uptake (requirement: uptake above liver in target lesions); strata not specified
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
44

Eligibility

Recruits 44 Vulnerable population flag selected in CTIS. However the protocol inclusion criteria restrict participation to adults ≥18 years. Informed consent is required from adult participants (adult main ICF documents provided). Country-specific ICFs and information sheets are provided (multiple languages). A Child Assent document exists among the submission documents (France), and there are follow-up and partner information sheets for pregnant participants/partners, but children are not eligible per inclusion criteria. Consent/assent handling: adult participants provide informed consent using country/language-specific ICFs; additional informational documents for female partners, pregnancy follow-up and (where present) child assent templates are provided for regulatory completeness..

Pregnancy Exclusion
For Phase II part only · Pregnant or breast-feeding women · Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) UNLESS they are using highly effective methods of contraception throughout the study and for up to 7 months after the last administration of [177Lu]Lu-NeoB or 6 months after the last dose of capecitabine (or as per locally prescribing information) whichever is longer.
Vulnerable Population
Vulnerable population flag selected in CTIS. However the protocol inclusion criteria restrict participation to adults ≥18 years. Informed consent is required from adult participants (adult main ICF documents provided). Country-specific ICFs and information sheets are provided (multiple languages). A Child Assent document exists among the submission documents (France), and there are follow-up and partner information sheets for pregnant participants/partners, but children are not eligible per inclusion criteria. Consent/assent handling: adult participants provide informed consent using country/language-specific ICFs; additional informational documents for female partners, pregnancy follow-up and (where present) child assent templates are provided for regulatory completeness.

Inclusion criteria

  • {"criterion_text":"- Participant is female or male adult ≥ 18 years old at the time of informed consent(s)\n- For Phase I part and stand alone Japanese cohort only: Female participant must be in postmenopausal status at the time of starting study treatment, as defined in Section 5.1 Male participants, provided that they do not require continued GnRHas while on study treatment For Phase II part only Female participant is post-menopausal as per criteria above at the time of starting study treatment. Female participant is pre/peri-menopausal at the time of starting study treatment, as defined in Section 5.1 Male participants, regardless of their need of GnRHas while on study treatment.\n- Participant has a histologically and/or cytologically documented diagnosis of ER+ breast cancer (ER expression >10% of tumor cell nuclei stain (regardless of PgR expression) (based on the most recently analyzed tissue sample tested by a local laboratory).\n- Participant has HER2- breast cancer defined as a negative in situ hybridization test (ISH) or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative ISH (e.g., FISH, CISH, or SISH) (based on the most recently analyzed tissue sample tested by a local laboratory) is required.\n- Participant received no more than three prior endocrine therapy/ies (single agent or in combination with targeted therapy) regimen/s in the metastatic setting of which at least one included endocrine therapy in combination with a CDK4/6i. In addition: - In case of confirmed presence of deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation, the participant may also have received a PARP inhibitor-based therapy. - In case of HER2-low breast cancer, the participant may also have received Enhertu®. Note: disease progression while on adjuvant ET (with or without CDK4/6i) or within 12 months of completing adjuvant endocrine therapy (with or without CDK4/6i), will be considered a line of therapy.\n- Participant has metastatic breast cancer with radiologically confirmed progression of disease after the most recent therapy\n- Participant must have measurable disease, i.e., at least one measurable lesion as per RECIST 1.1. (a lesion at a previously irradiated site may only be counted as a target lesion if there is a clear sign of progression since the irradiation) as per local assessment. Note: If only lytic bone lesions are present, they must have at least one lesion with a soft tissue component that can be evaluated by CT or MRI and meets the definition of measurability as per RECIST 1.1 criteria (participants with only one predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation).\n- Participant has at least one target lesion [as per RECIST 1.1 and based on the baseline contrast-enhanced CT (or MRI)] with [68Ga]Ga-NeoB uptake above the liver at PET/CT or PET/MRI, as per local reading. In addition: Participant with liver or lung disease involvement must show [68Ga]Ga-NeoB uptake above the liver as follows: If there is liver disease involvement (in the absence of lung involvement), in ≥ 50% of all CT measurable liver lesions (RECIST 1.1) If there is lung disease involvement (in the absence of liver involvement), in ≥ 50% of all CT measurable lung lesions (RECIST 1.1) Participants with both liver and lung disease involvement must show [68Ga]Ga-NeoB uptake above the liver in ≥ 50% of all CT measurable lesions either in liver or lung (RECIST 1.1) and in at least one measurable lesion in the remaining organ (lung or liver)\n- Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n- Participant has adequate bone marrow and organ function as defined by laboratory values in section 5.1 (as assessed by local laboratory)."}

Exclusion criteria

  • {"criterion_text":"- Participant with symptomatic visceral disease or any disease burden that are at risk of life-threatening complications as per the investigator’s judgment.\n- Sexually active male participants unwilling to: remain abstinent (refrain from sexual intercourse) or use a condom, while taking study treatment and for at least 4 months after the last administration of [177Lu]Lu-NeoB, or 3 months after the last dose of capecitabine (or as per locally prescribing information) whichever is longer, in addition to the highly effective method used by the partner who is a female of child-bearing potential.\n- For Phase II part only ·\tPregnant or breast-feeding women ·\tWomen of childbearing potential (defined as all women physiologically capable of becoming pregnant) UNLESS they are using highly effective methods of contraception throughout the study and for up to 7 months after the last administration of [177Lu]Lu-NeoB or 6 months after the last dose of capecitabine (or as per locally prescribing information) whichever is longer.\n- Participant has received >1 prior treatment with chemotherapy and/or Antibody Drug Conjugate (ADCs) in the metastatic setting. Chemotherapy in neoadjuvant/ adjuvant setting is not considered a line of therapy, unless progression or recurrence occurred during or within 12 months after completion of adjuvant chemotherapy).\n- Participant has received prior treatment with capecitabine\n- Participant has inflammatory breast cancer at screening.\n- Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, cause unacceptable safety risks, contraindicate participant participation in the clinical study or compromise compliance with the protocol\n- History or current diagnosis of impaired cardiac function, clinically significant cardiac disease or ECG abnormalities\n- Participant is currently receiving brivudine which cannot be discontinued at least 4-week prior to start of capecitabine therapy.\n- Participant is currently receiving NEP inhibitors (i.e., Entresto®) and images for dosimetry assessments cannot be acquired for this participant as per Section 8.7.3 of the protocol.\n- Participant with known deficiency or family history of deficiency of dihydropyrimidine dehydrogenase."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Phase I: Incidence and severity of AEs including dose limiting toxicities (DLTs), serious Adverse Events (SAEs), changes in laboratory parameters, vital signs and ECGs Tolerability: Dose interruptions, discontinuations, and reductions Phase II: ORR, CBR, TTR, DOR, PFS as per RECIST v1.1 by local investigator assessment Overall Survival (OS)","definition_or_measurement_approach":"Phase I safety endpoints assessed by incidence and severity of AEs (including DLTs, SAEs), laboratory parameters, vital signs and ECGs; tolerability assessed by dose interruptions, discontinuations and reductions. Phase II efficacy endpoints (ORR, CBR, TTR, DOR, PFS) assessed as per RECIST v1.1 by local investigator assessment; Overall Survival (OS) measured as time from randomization/first treatment to death."}

Secondary endpoints

  • {"endpoint_text":"- Phase I and II: ● Time activity curves (TACs) and absorbed radiation doses of [177Lu]Lu-NeoB in organs and tumor lesions ● Concentration of [177Lu]Lu-NeoB in blood over time and derived PK parameters","definition_or_measurement_approach":"Dosimetry: time-activity curves and absorbed radiation doses in organs and tumor lesions; PK: blood concentration over time and derived pharmacokinetic parameters."}
  • {"endpoint_text":"- Phase I and II: ● Incidence and severity of adverse events following [68Ga]Ga-NeoB administration at screening","definition_or_measurement_approach":"Safety monitoring of adverse events following [68Ga]Ga-NeoB administration at screening; incidence and severity captured per standard AE/SAE reporting."}
  • {"endpoint_text":"- Phase I and II: ● Positive Percent Agreement (PPA) and Positive Predictive Agreement (PPrA) using conventional imaging as reference by central assessment, at screening","definition_or_measurement_approach":"Diagnostic concordance between [68Ga]Ga-NeoB PET and conventional imaging assessed centrally using PPA and PPrA metrics at screening."}
  • {"endpoint_text":"- Phase I only: ● Visual assessment of image quality by central assessment","definition_or_measurement_approach":"Central visual assessment of image quality for Phase I imaging evaluations."}
  • {"endpoint_text":"- Phase I only: ● ORR, CBR, TTR, DOR, PFS as per RECIST v1.1 by local investigator assessment ● OS","definition_or_measurement_approach":"Efficacy endpoints per RECIST v1.1 by local investigator assessment; OS measured as survival time."}
  • {"endpoint_text":"- Phase II only: ● Incidence and severity of AEs, SAEs, changes in laboratory parameters, vital signs and ECGs Dose interruptions, discontinuations, and reductions","definition_or_measurement_approach":"Safety and tolerability assessments in Phase II by standard AE/SAE reporting and recording of dose modifications."}

Recruitment

Registry Or Advocacy Recruitment
True, Fundacion General De La Universidad De Malaga (Patient organisation/association) is listed as a third party involved in sponsor duties
Planned Sample Size
44
Recruitment Window Months
86
Consent Approach
Informed consent obtained from adult participants using country- and language-specific ICFs (Main ICF - Adult documents provided per country). Documents include ICFs and information sheets for adult participants, follow-up ICFs for pregnant participants/partners, and information sheets for female partners. Languages and country-specific ICFs present include Italian, German, Spanish, French, Portuguese, Dutch and Polish (and English patient-facing summaries). A Child Assent template is present among submission documents (France) though children are excluded by inclusion criteria. Separate data protection consent forms and optional assessments/addenda are included where applicable.

Methods

  • Country-specific recruitment arrangements documented (K1 submissions exist for Italy, Germany, Spain, France, Portugal, Netherlands) - implies local recruitment processes per country.
  • Advertisements (K2 documents) - country/language specific advertisement materials were submitted (examples: Italy - Italian; Germany - German; Spain - Spanish; France - French; Portugal - Portuguese; Netherlands - Dutch).
  • Patient Recruitment Materials provided by Jumo Health USA Inc. (listed as third party with duty 'Patient Recruitment Materials').

Geography

Total Number Of Sites
17
Total Number Of Participants
40

Italy

Earliest CTIS Part Ii Submission Date
12-01-2024
Latest Decision Or Authorization Date
23-04-2024
Processing Time Days
102
Number Of Sites
2
Number Of Participants
5

Sites

Site Name
Azienda USL IRCCS Di Reggio Emilia
Department Name
4202: Oncology and High Technology Department, Nuclear Medicine Unit
Principal Investigator Name
Angelina Filice
Principal Investigator Email
angelina.filice@ausl.re.it
Contact Person Name
Angelina Filice
Contact Person Email
angelina.filice@ausl.re.it
Number Of Participants
5
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
4201: Nuclear Medicine
Principal Investigator Name
Federica Matteucci
Principal Investigator Email
federica.matteucci@irst.emr.it
Contact Person Name
Federica Matteucci
Contact Person Email
federica.matteucci@irst.emr.it

Germany

Earliest CTIS Part Ii Submission Date
11-03-2024
Latest Decision Or Authorization Date
23-04-2024
Processing Time Days
43
Number Of Sites
4
Number Of Participants
8

Sites

Site Name
Universitaetsklinikum Essen AöR
Department Name
4101:Klinik fuer Nuklearmedizin
Principal Investigator Name
Ken Herrmann
Principal Investigator Email
Ken.herrmann@uk-essen.de
Contact Person Name
Ken Herrmann
Contact Person Email
Ken.herrmann@uk-essen.de
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
4103:Frauenklinik mit Poliklinik
Principal Investigator Name
Peter Fasching
Principal Investigator Email
peter.fasching.studien@uk-erlangen.de
Contact Person Name
Peter Fasching
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
4104:Nuklearmedizin und Klinische Molekulare Bildgebung
Principal Investigator Name
Christian Lafougère
Principal Investigator Email
christian.lafougere@med.uni-tuebingen.de
Contact Person Name
Christian Lafougère
Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
4102:Klinik und Poliklinik für Nuklearmedizin
Principal Investigator Name
Matthias Eiber
Principal Investigator Email
matthias.eiber@tum.de
Contact Person Name
Matthias Eiber
Contact Person Email
matthias.eiber@tum.de
Number Of Participants
8

Spain

Earliest CTIS Part Ii Submission Date
19-02-2024
Latest Decision Or Authorization Date
23-04-2024
Processing Time Days
64
Number Of Sites
4
Number Of Participants
13

Sites

Site Name
Hospital Universitario 12 De Octubre
Department Name
4503:Servicio Oncología
Principal Investigator Name
Manuel Alva Bianchi
Principal Investigator Email
manuel.alva@salud.madrid.org
Contact Person Name
Manuel Alva Bianchi
Contact Person Email
manuel.alva@salud.madrid.org
Site Name
Hospital Clinic De Barcelona
Department Name
4501:Servicio Oncología
Principal Investigator Name
Maria Jesús Vidal Losada
Principal Investigator Email
mjvidal@clinic.cat
Contact Person Name
Maria Jesús Vidal Losada
Contact Person Email
mjvidal@clinic.cat
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
4504:Servicio Oncología
Principal Investigator Name
Marta Benavent Viñuales
Principal Investigator Email
marta.benavent.sspa@juntadeandalucia.es
Contact Person Name
Marta Benavent Viñuales
Site Name
Institut Catala D'oncologia
Department Name
4502:Servicio Oncología
Principal Investigator Name
Rafael Villanueva Vazquez
Principal Investigator Email
ravillanueva@iconcologia.net
Contact Person Name
Rafael Villanueva Vazquez
Contact Person Email
ravillanueva@iconcologia.net
Number Of Participants
13

France

Earliest CTIS Part Ii Submission Date
05-03-2024
Latest Decision Or Authorization Date
29-04-2024
Processing Time Days
55
Number Of Sites
5
Number Of Participants
8

Sites

Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
4004: Medecine Nucleaire
Principal Investigator Name
Loic DJAILEB
Principal Investigator Email
ldjaileb@chu-grenoble.fr
Contact Person Name
Loic DJAILEB
Contact Person Email
ldjaileb@chu-grenoble.fr
Site Name
Centre Regional Lutte Contre Le Cancer
Department Name
4005: Oncologie medicale
Principal Investigator Name
Laura BENDER-SOMME
Principal Investigator Email
l.bender@icans.eu
Contact Person Name
Laura BENDER-SOMME
Contact Person Email
l.bender@icans.eu
Site Name
Institut Gustave Roussy
Department Name
4007: Medecine Nucleaire
Principal Investigator Name
Desiree DEANDREIS
Principal Investigator Email
desiree.deandreis@gustaveroussy.fr
Contact Person Name
Desiree DEANDREIS
Site Name
Institut De Cancerologie De L Ouest
Department Name
4001: Oncologie
Principal Investigator Name
Mario CAMPONE
Principal Investigator Email
Mario.campone@ico.unicancer.fr
Contact Person Name
Mario CAMPONE
Contact Person Email
Mario.campone@ico.unicancer.fr
Site Name
Institut Bergonie
Department Name
4006: Medecine Nucleaire
Principal Investigator Name
Paul SCHWARTZ
Principal Investigator Email
p.schwartz@bordeaux.unicancer.fr
Contact Person Name
Paul SCHWARTZ
Number Of Participants
8

Portugal

Earliest CTIS Part Ii Submission Date
04-04-2024
Latest Decision Or Authorization Date
26-04-2024
Processing Time Days
22
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Instituto Portugues De Oncologia Do Porto Francisco Gentil E.P.E.
Department Name
4401: Serviço de Oncologia Médica
Principal Investigator Name
Ana Ferreira
Contact Person Name
Ana Ferreira
Number Of Participants
3

Netherlands

Earliest CTIS Part Ii Submission Date
12-04-2024
Latest Decision Or Authorization Date
23-04-2024
Processing Time Days
11
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Reinier de Graaf Groep
Department Name
4301: Oncology
Principal Investigator Name
Lemonitsa Mammatas
Principal Investigator Email
l.mammatas@rdgg.nl
Contact Person Name
Lemonitsa Mammatas
Contact Person Email
l.mammatas@rdgg.nl
Number Of Participants
3

Sponsor

Primary sponsor

Full Name
Novartis Pharma AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
Parexel International (IRL) Limited
Responsibilities
Role code 12 (clinical operations/monitoring functions as indicated in sponsor duties)
Name
Syneos Health Inc.
Responsibilities
Clinical operations support (sponsor duties code 1)
Name
Icon Clinical Research Limited
Responsibilities
Clinical operations support (sponsor duties code 1)
Name
IQVIA Limited / Iqvia Rds Inc.
Responsibilities
Randomization, management of drug supply logistics, dispensing, unblinding, ECG analysis and other trial support functions

Third parties

  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Database management and quality control","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Charles River Laboratories Edinburgh Limited","duties_or_roles":"Pharmacokinetics HPLC","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Invicro LLC","duties_or_roles":"Imaging for Dosimetry and Response Assessments","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"Management of drug supply logistics, dispensing, and unblinding. Randomization of patients.","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Services (sponsor duties code: 1)","organisation_type":"Pharmaceutical company"}
  • {"country":"Spain","full_name":"Advanced Accelerator Applications Iberica S.L.","duties_or_roles":"Role code 14 (specific duty text provided in sponsor documentation)","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"Role code 12","organisation_type":"Pharmaceutical company"}
  • {"country":"Spain","full_name":"Fundacion General De La Universidad De Malaga","duties_or_roles":"Role code 14 (patient organisation involvement)","organisation_type":"Patient organisation/association"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Role code 1","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)","duties_or_roles":"Role code 14 (trial pharmacy role)","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Sample storage; provision of sample collection kits","organisation_type":"Pharmaceutical company"}
  • {"country":"Spain","full_name":"Advanced Accelerator Applications Molecular Imaging Iberica S.L.","duties_or_roles":"Role code 14","organisation_type":"Pharmaceutical company"}
  • {"country":"Portugal","full_name":"Advanced Accelerator Applications (Portugal) Unipessoal Lda.","duties_or_roles":"Central RadioPharmacy","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"Electronic Patient Reported Outcomes (ePRO) formatting, translations, and licensing","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Clinical trial services including ECG analysis and other CRO services","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"Drug distribution, storage, relabeling, return and destruction","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"Patient Recruitment Materials","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Germany","full_name":"Saale-Apotheke Dr. Christian Wegner e.Kfm.","duties_or_roles":"Role code 14 (radio pharmacy role)","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Bbk Worldwide LLC","duties_or_roles":"Patient Reimbursement for Germany","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Kayentis","duties_or_roles":"Coordination of licensing, translation and development of electronic patient reported outcomes (PROs). Data capture and cleaning of completed PROs.","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"ePRO formatting/translations (duplicate entry consolidated)","organisation_type":"Pharmaceutical company"}
  • {"country":"Spain","full_name":"Advanced Accelerator Applications Iberica S.L. (Molecular Imaging)","duties_or_roles":"Role code 14 (radiopharmacy/imaging support)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
CAPECITABINE
Active Substance
CAPECITABINE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus:2
Investigational Product Name
[177Lu]-NeoB solution for infusion
Active Substance
LUTETIUM (177LU)-NEOBOMB1
Modality
Radiopharmaceutical
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS
Authorisation Status
prodAuthStatus:1
Investigational Product Name
AAA503
Active Substance
NEOB
Modality
Radiopharmaceutical (kit for radiopharmaceutical preparation)
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS
Authorisation Status
prodAuthStatus:1
Orphan Designation
Yes
Combination Treatment
Yes

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