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DESTINY-Breast07 - A Phase 1b/2 Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With HER2-positive Metastatic Breast Cancer - D967JC00001

Studio Clinico

Patologia: Neoplasie della mammella

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: 

Fase di studio: 1, I B, II

Richiesta mandatoria di tessuto: 

Linee di trattamento: Prima linea, Seconda linea, Terza/N linea

Criteri di inclusione: 

- Patients must be at least 18 years of age
- Pathologically documented breast cancer that:
    - 1. Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic
    - 2. HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment
    - 3. Is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting
- Patient must have adequate tumor sample for biomarker assessment
- ECOG Performance Status of 0 or 1

Part 1
- 1. Disease progression on or after the last systemic therapy prior to starting study treatment
- 2. At least 1 prior treatment line in metastatic setting required.

Part 2 (Modules 0 - 5)

- a) No prior lines of therapy for advanced/MBC allowed

Part 2 (Module 6 and 7) a) Zero or one prior lines of therapy for advanced/MBC allowed

CNS Inclusion
- Modules 0 - 5 Patients must have no brain metastases or stable brain metastases.
- Module 6 and 7 Patients must have untreated brain metastases not needing local therapy or previously treated brain metastases that have progressed since prior local therapy.

Criteri di esclusione: 

- Uncontrolled or significant cardiovascular disease
- Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
- Lung-specific intercurrent clinically significant illnesses
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Spinal cord compression or a history of leptomeningeal carcinomatosis
- Prior treatment with immune checkpoint inhibitors
- Prior treatment with an ADC containing a topoisomerase I inhibitor
- Prior treatment with tucatinib

CNS Exclusion
- Modules 0 - 5: Has untreated brain metastasis
- Module 6 and 7: Ongoing use of systemic corticosteroids for control of symptoms of brain metastases or brain lesion thought to require immediate local therapy.

Schema di trattamento: 

Drug: Trastuzumab deruxtecan
Drug: Durvalumab
Drug: Paclitaxel
Drug: Pertuzumab
Drug: Tucatinib

Trattamento sperimentale: 

Module 1- T-DXd and Durvalumab
Module 2- T-DXd and Pertuzumab
Module 3- T-DXd and Paclitaxel
Module 4- T-DXd and Durvalumab and Paclitaxel
Module 0- T-DXd
Module 5- T-DXd and Tucatanib
Module 6- T-DXd and Tucatinib
Module 7- T-DXd in patients with active brain metastases

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

- Occurrence of adverse events (AEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 53 months ]
Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0
- Occurrence of serious adverse events (SAEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 53 months ]
Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0
- Occurrence of adverse events (AEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 53 months ]
Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0
- Occurrence of serious adverse events (SAEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 53 months ] Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0

Obiettivi secondari dello studio: 

- Objective Response Rate (ORR)- Part 2 [ Time Frame: Until progression, assessed up to approximately 53 months ]
ORR is defined as the proportion of patients who have a CR or PR, as determined by the Investigator at local site per RECIST 1.1.
- Progression Free Survival (PFS)- Part 2 [ Time Frame: Until progression, assessed up to approximately 53 months ]
PFS is defined as time from the date of randomization until the date of progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause.
- Progression Free Survival 2 (PFS2)- Part 2 [ Time Frame: Assessed up to approximately 53 months ]
PFS2 is defined as time from the date of randomisation until the date of progression on next line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy) or death; second progression will be defined according to local standard clinical practice.
- Duration of Response (DoR)- Part 2 [ Time Frame: Until progression, assessed up to approximately 53 months ]
DoR is defined as time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
- Overall Survival (OS)- Part 2 [ Time Frame: Until death, assessed up to approximately 53 months ]
OS is defined as time from the date of randomisation until the date of death due to any cause.
- Serum Concentration of Trastuzumab Deruxtecan (T-DXd) [ Time Frame: While on study drug up to study completion, approximately 53 months ]
Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
- Serum Concentration of Durvalumab [ Time Frame: While on study drug up to study completion, approximately 53 months ]
Determination of durvalumab concentration in serum at different time points after administration
- Serum Concentration of Pertuzumab [ Time Frame: While on study drug up to study completion, approximately 53 months ]
Determination of pertuzumab concentration in serum at different time points after administration
- Plasma Concentration of Paclitaxel [ Time Frame: While on study drug up to study completion, approximately 53 months ]
Determination of paclitaxel concentration in plasma at different time points after administration
- Plasma Concentration of Tucatinib [ Time Frame: While on study drug up to study completion, approximately 53 months ]
Determination of tucatinib concentration in plasma at different time points after administration
- Immunogenicity of trastuzumab deruxtecan [ Time Frame: Up to follow-up period, approximately 53 months ]
Percentage of patients who develop ADA for trastuzumab deruxtecan
- Immunogenicity of Durvalumab [ Time Frame: Up to follow-up period, approximately 53 months ]
Percentage of patients who develop ADA for durvalumab
- Immunogenicity of Pertuzumab [ Time Frame: Up to follow-up period, approximately 53 months ]
Percentage of patients who develop ADA for pertuzumab.

Centri partecipanti

Nord Italia

Ospedale S.Orsola Malpighi, Università di Bologna
Via Pietro Albertoni 15 - 40138 Bologna - BO

 

Istituto Europeo di Oncologia
Via Ripamonti 435 - 20141 Milano - MI

Riferimento: Prof. Giuseppe Curigliano
Telefono: 0257489599
Email: giuseppe.curigliano@ieo.it

 

Centro Italia

Fondazione Policlinico A. Gemelli
Largo Agostino Gemelli 8 - 00168 Roma - RM

 

Sud Italia e isole

Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA

Informazioni Generali

Protocollo

Numero di iscrizione a registro: NCT04538742

Data di inserimento: 24.02.2022

Promotore

AstraZeneca

Principal Investigator ITALIA

IEO - Istituto Europeo di Oncologia, Milano

Riferimento: Prof. Giuseppe Curigliano

Telefono: 0257489599

Email: giuseppe.curigliano@ieo.it

Localita: Milano

 

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