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JOURNAL ONKOLOGIE – STUDIE
DB-07

A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer

Rekrutierend

NCT-Nummer:
NCT04538742

Studienbeginn:
Dezember 2020

Letztes Update:
25.03.2021

Wirkstoff:
Trastuzumab Deruxtecan, Durvalumab, Paclitaxel, Pertuzumab, Tucatinib

Indikation (Clinical Trials):
Breast Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
AstraZeneca

Collaborator:
Daiichi Sankyo Company, Limited

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 74)

Research Site
12200 Berlin
(Berlin)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
46236 Bottrop
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
40225 Düsseldorf
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
91054 Erlangen
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
81675 München
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
97080 Würzburg
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
51101 Saint Paul
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
11725 Commack
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
10016 New York
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
27599-7097 Chapel Hill
United StatesZurückgezogen» Google-Maps
Research Site
84112 Salt Lake City
United StatesZurückgezogen» Google-Maps
Research Site
22031 Fairfax
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
14784-400 Barretos
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
30150-270 Belo Horizonte
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
90610-000 Porto Alegre
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
91350-200 Porto Alegre
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
20560-120 Rio de Janeiro
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
01317-001 Sao Paulo
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
04029-000 Sao Paulo
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
18030-510 Sorocaba
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
94805 Villejuif Cedex
FranceNoch nicht rekrutierend» Google-Maps
Research Site
111123 Moscow
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
115478 Moscow
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
117997 Moscow
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
121205 Moscow
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
195271 Saint Petersburg
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
197758 Sankt-Peterburg
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
08908 L'Hospitalet de Llobregat
SpainNoch nicht rekrutierend» Google-Maps
Research Site
IG9 5HX Buckhurst Hill
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
CB2 2QQ Cambridge
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
EC1A 7BE London
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
SE19RT London
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
OX3 7LE Oxford
United KingdomNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

This study is modular in design allowing assessment of safety, tolerability and anti-tumour

activity of T-DXd in combination with other anti-cancer agents. Combination-treatment modules

will have 2 parts: a dose-finding phase (Part 1), and a dose expansion phase (Part 2); the

recommended Phase 2 dose (RP2D) determined in Part 1 will be used for the dose-expansion in

Part 2.

The target population of interest in this study is patients with HER2-positive (as per

ASCO/CAP 2018 guidelines) advanced/MBC inclusive of patients with active and stable brain

metastases. Part 1 of each module will enroll patients with locally assessed HER2-positive

advanced/MBC in second-line or later patients. Part 2 of each module will enroll patients

with locally assessed HER2-positive breast cancer who have not received prior treatment for

advanced/metastatic disease.

Ein-/Ausschlusskriterien

Key Inclusion Criteria:

- 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

Key Exclusion Criteria:

- 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

Studien-Rationale

Primary outcome:

1. 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

2. 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

3. 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

4. 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

Secondary outcome:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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

7. 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

8. 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

9. 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

10. 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

11. Immunogenicity of trastuzumab deruxtecan (Time Frame - Up to follow-up period, approximately 53 months):
Percentage of patients who develop ADA for trastuzumab deruxtecan

12. Immunogenicity of Durvalumab (Time Frame - Up to follow-up period, approximately 53 months):
Percentage of patients who develop ADA for durvalumab

13. Immunogenicity of Pertuzumab (Time Frame - Up to follow-up period, approximately 53 months):
Percentage of patients who develop ADA for pertuzumab

Studien-Arme

  • Experimental: Module 1- T-DXd and Durvalumab
    T-DXd and Durvalumab
  • Experimental: Module 2- T-DXd and Pertuzumab
    T-DXd and Pertuzumab
  • Experimental: Module 3- T-DXd and Paclitaxel
    T-DXd and Paclitaxel
  • Experimental: Module 4- T-DXd and Durvalumab and Paclitaxel
    T-DXd and Durvalumab and Paclitaxel
  • Experimental: Module 0- T-DXd
    T-DXd
  • Experimental: Module 5 - T-DXd and Tucatanib
    T-DXd and tucatinib
  • Experimental: Module 6 - T-DXd and Tucatinib
    T-DXd and tucatinib in patients with active brain metastases (Part 2 Only)
  • Experimental: Module 7 - T-DXd
    T-DXd monotherapy in patients with active brain metastases (Part 2 Only)

Geprüfte Regime

  • Trastuzumab deruxtecan (DS-8201a, T-DXd):
    T-DXd: administered as an IV infusion
  • Durvalumab (MEDI4736):
    Durvalumab: administered as an IV infusion
  • Paclitaxel:
    Paclitaxel: administered as an IV infusion
  • Pertuzumab:
    Pertuzumab: administered as an IV infusion
  • Tucatinib (ONT-380):
    Tucatinib administered orally (tablet) twice daily

Quelle: ClinicalTrials.gov


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