- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT02575781
A Study of SAR428926 in Patients With Advanced Solid Tumors
A First-in-human Phase 1 Dose Escalation Study of SAR428926 in Patients With Advanced Solid Tumors
Primary Objectives:
To determine the maximum tolerated dose (MTD) of SAR428926 when administered as a single agent in patients with advanced solid tumors.
To evaluate the anti-tumor response of SAR428926 when administered as a single agent in patients with advanced triple negative breast cancer (TNBC) positive for the protein targeted by SAR428926 To assess the preliminary anti-tumor response of SAR428926 when administered as a single agent in patients with advanced solid tumors positive for the protein targeted by SAR428926
Secondary Objectives:
To determine the overall safety profile of SAR428926 as a single agent. To characterize the pharmacokinetics (PK) profile of SAR428926 and its metabolites.
To identify the recommended Phase 2 dose (RP2D) of SAR428926 as a single agent. To evaluate the immunogenicity of SAR428926. To assess the tumor response and duration of tumor response in all treated patients.
To evaluate the benefit of primary prophylaxis on the occurrence of corneal (keratopathy/keratitis) toxicity (Expansion cohorts).
Panoramica dello studio
Descrizione dettagliata
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 1
Contatti e Sedi
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion criteria :
- Patients with advanced solid tumor with no standard alternative treatment.
- Availability of archived tumor tissue for SAR428926 targeted antigen testing.
- For participants in the Escalation Phase: human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC), gastric cancer, colorectal cancer (CRC), ovarian cancer, prostate cancer and non small-cell lung cancer (NSCLC).
- For participants in the Expansion Phase: patients with TNBC, prostate cancer, CRC, ovarian cancer or NSCLC and positive SAR428926 targeted antigen.
- At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and one lesion amenable to biopsy in expansion cohort only (except for NSCLC patients).
Exclusion criteria:
- Age less than 18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status more than 1.
- New or progressing brain metastases.
- Concurrent treatment with any other anticancer therapy or inadequate wash-out period for prior anticancer therapies, including other experimental anticancer treatment, before first administration of SAR428926, or non resolution of toxicities induced by these anticancer therapies.
- Women of reproductive potential and male subjects with female partners of childbearing potential who are not willing to avoid pregnancy.
- Pregnancy or breast feeding.
- Prior maytansinoid treatments (DM1 or DM4 antibody drug conjugates [ADCs]).
- Unwillingness and inability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
- Significant concomitant illness, including psychiatric condition that, in the opinion of the Investigator or Sponsor, would adversely affect the patient's participation in the study.
- Any surgery within the preceding 3 weeks.
- Known human immunodeficiency virus (HIV) infection or active hepatitis B or C viral infection.
- Poor bone marrow reserve.
- Poor kidney and liver function.
- Previous history of chronic corneal diseases (even if asymptomatic) or unresolved acute non-recurrent corneal conditions. Patients wearing contact lenses who are not willing to stop wearing them for the duration of the study.
- Unresolved signs and symptoms of peripheral neuropathy; Grade 1 is acceptable.
- Abnormal cardiac function defined by a left ventricular ejection fraction (LVEF) <50%.
- Known intolerance to infused protein products including other monoclonal antibodies and ADCs.
- Medical conditions requiring concomitant administration of medications with narrow therapeutic window, metabolized by CYPs and which a dose reduction cannot be considered.
- Medical conditions requiring concomitant administration of strong CYP3A inhibitors, unless it can be discontinued at least two weeks before first administration of SAR428926.
- Other prior neoplasm.
- Contraindications to the use of ophthalmic vasoconstrictor and/or corticosteroid as per package insert of each drug, including the following: increase intraocular pressure, prior or current glaucoma, narrow-angle glaucoma, ongoing eye infection, uncontrolled hypertension, known/suspected allergy to constituents of the preparation (such as sodium bisulfite).
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: SAR428926-Escalating cohort
SAR428926 will be administered intravenously up to disease progression or dose limiting toxicities
|
Pharmaceutical form:concentrate for solution for infusion Route of administration: intravenous
|
Sperimentale: SAR428926 in triple negative breast cancer-Expansion Cohort 1
SAR428926 will be administered intravenously at maximum tolerated dose (MTD) up to disease progression or unacceptable toxicity
|
Pharmaceutical form:concentrate for solution for infusion Route of administration: intravenous
|
Sperimentale: SAR428926 in solid tumors-Expansion Cohort 2
SAR428926 will be administered intravenously at the MTD up to disease progression or unacceptable toxicity
|
Pharmaceutical form:concentrate for solution for infusion Route of administration: intravenous
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
---|---|
Number of patients with dose limiting adverse events (Escalation cohort)
Lasso di tempo: 4 weeks
|
4 weeks
|
Number of patients with corneal adverse events impacting study treatment (Escalation cohort)
Lasso di tempo: 8 weeks
|
8 weeks
|
Assessment of overall response rate using standard imaging and RECIST v1.1 criteria (Expansion cohort)
Lasso di tempo: Tumor assessment every 2 months until disease progression or up to 36 months, whichever came first
|
Tumor assessment every 2 months until disease progression or up to 36 months, whichever came first
|
Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
---|---|
Number of treatment emergent adverse events
Lasso di tempo: Up to 3 years
|
Up to 3 years
|
Assessment of PK parameter: maximum concentration (Cmax)
Lasso di tempo: 2 months
|
2 months
|
Assessment of PK parameter: time to reach maximum concentration (tmax)
Lasso di tempo: 2 months
|
2 months
|
Assessment of PK parameter: trough plasma concentration (Ctrough)
Lasso di tempo: Every 2 weeks until approximately 14 weeks
|
Every 2 weeks until approximately 14 weeks
|
Assessment of PK parameter: area under the plasma concentration curve versus time curve between 1 and 14 days (AUC0-14 day)
Lasso di tempo: 2 months
|
2 months
|
Assessment of PK parameter: mean systemic clearance (CL)
Lasso di tempo: 2 months
|
2 months
|
Assessment of PK parameter: clearance at steady state (CLss)
Lasso di tempo: 2 months
|
2 months
|
Assessment of PK parameter: accumulation ratio on AUC0-14
Lasso di tempo: 2 months
|
2 months
|
Assessment of PK parameter: accumulation ratio on Cmax
Lasso di tempo: 2 months
|
2 months
|
Preliminary tumor response by RECIST v1.1 (Escalation)
Lasso di tempo: 2 months
|
2 months
|
Number of corneal events according to the presence or not of preventive measures
Lasso di tempo: 12 weeks
|
12 weeks
|
Collaboratori e investigatori
Sponsor
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- TED14147
- 2015-001441-92 (Numero EudraCT)
- U1111-1168-4706 (Altro identificatore: UTN)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .