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JOURNAL ONKOLOGIE – STUDIE
CAPItello-292

Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)

Rekrutierend

NCT-Nummer:
NCT04862663

Studienbeginn:
Mai 2021

Letztes Update:
16.04.2024

Wirkstoff:
Capivasertib, Fulvestrant, Palbociclib, Ribociclib, Abemaciclib

Indikation (Clinical Trials):
Breast Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
AstraZeneca

Collaborator:
-

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com» Kontaktdaten anzeigen
AZ Breast Cancer Study Navigators
Kontakt:
Phone: +1-877-400-4656
E-Mail: AstraZeneca@CareboxHealth.com» Kontaktdaten anzeigen

Studienlocations
(3 von 228)

Research Site
86150 Augsburg
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
10967 Berlin
(Berlin)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
13125 Berlin
(Berlin)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
46236 Bottrop
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
01307 Dresden
(Sachsen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
91054 Erlangen
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
79106 Freiburg
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
49124 Georgsmarienhütte
(Niedersachsen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
20357 Hamburg
(Hamburg)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
30625 Hannover
(Niedersachsen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
74078 Heilbronn
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
24105 Kiel
(Schleswig-Holstein)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
04103 Leipzig
(Sachsen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
68167 Mannheim
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
41061 Mönchengladbach
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
48149 Münster
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
93053 Regensburg
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
21680 Stade
(Niedersachsen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
54290 Trier
(Rheinland-Pfalz)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
85719 Tucson
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
90033 Los Angeles
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
90048 Los Angeles
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
93105 Santa Barbara
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
06510 New Haven
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
19713 Newark
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
46804 Fort Wayne
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
40202 Louisville
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
21401 Annapolis
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
02215 Boston
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
48236 Detroit
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
63110 Saint Louis
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
08103 Camden
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
10016 New York
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
10065 New York
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
97030 Gresham
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
15213 Pittsburgh
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
75246 Dallas
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
76104 Fort Worth
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
77030 Houston
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
78240 San Antonio
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
22042 Falls Church
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
20176 Leesburg
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
23114 Midlothian
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
23502 Norfolk
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
1439 Buenos Aires
ArgentinaNoch nicht rekrutierend» Google-Maps
Research Site
B6620LUD Chivilcoy
ArgentinaNoch nicht rekrutierend» Google-Maps
Research Site
6009 Nedlands
AustraliaAktiv, nicht rekrutierend» Google-Maps
Research Site
89010-340 Blumenau
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
90035-903 Porto Alegre
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
76834-899 Porto Velho
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
04014-002 São Paulo
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
12030-200 Taubaté
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
J1H 5N4 Sherbrooke
CanadaNoch nicht rekrutierend» Google-Maps
Research Site
441000 Xiangyang City
ChinaNoch nicht rekrutierend» Google-Maps
Research Site
63011 Clermont Ferrand
FranceNoch nicht rekrutierend» Google-Maps
Research Site
10408 Goyang-si
Korea, Republic ofNoch nicht rekrutierend» Google-Maps
Research Site
03080 Seoul
Korea, Republic ofNoch nicht rekrutierend» Google-Maps
Research Site
10350 George Town
MalaysiaNoch nicht rekrutierend» Google-Maps
Research Site
50586 Kuala Lumpur
MalaysiaNoch nicht rekrutierend» Google-Maps
Research Site
59100 Kuala Lumpur
MalaysiaNoch nicht rekrutierend» Google-Maps
Research Site
10450 Pulau Pinang
MalaysiaNoch nicht rekrutierend» Google-Maps
Research Site
85-796 Bydgoszcz
PolandAktiv, nicht rekrutierend» Google-Maps
Research Site
15706 Santiago de Compostela
SpainNoch nicht rekrutierend» Google-Maps
Research Site
10400 Ratchathewi
ThailandNoch nicht rekrutierend» Google-Maps
Research Site
CU2 7XX Guildford
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
700000 Ho Chi Minh city
VietnamNoch nicht rekrutierend» Google-Maps
Research Site
70000 Ho Chi Minh
VietnamNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

This Phase Ib/III study (CAPItello-292) aims to evaluate the efficacy, safety and the degree

of added benefit of capivasertib combined with CDK4/6i and fulvestrant in participants with

locally advanced (inoperable) or metastatic HR+/HER2- breast cancer. Although the dosing

regimens of capivasertib + fulvestrant and of CDK4/6i + fulvestrant are established

separately, the dose and schedule for the triplet combinations (capivasertib + CDK4/6i +

fulvestrant) need to be confirmed. Therefore, the initial dose finding Phase Ib part of the

study will determine the recommended Phase III doses (RP3D) of the triplet combinations. The

Phase III part of the study will evaluate the efficacy, safety and the degree of added

benefit of the triplet combinations of capivasertib and fulvestrant with investigator's

choice of CDK4/6i (either palbociclib or ribociclib at safe and tolerable doses, once

identified) in comparison with a control arm (fulvestrant + investigator's choice of CDK4/6i

[palbociclib or ribociclib]) in a ER+ HER2- maC high risk population that did not receive

prior endocrine therapy in the advanced setting.

Ein-/Ausschlusskriterien

Key inclusion criteria for both phases:

1. Adult females (pre-/peri-/ and post-menopausal), and adult males.

2. Histologically confirmed HR+/ HER2- breast cancer determined from the most recent

tumour sample (primary or metastatic) per the American Society of Clinical Oncology

and College of American Pathologists guideline. To fulfil the requirement of HR+

disease, a breast cancer must express ER with or without co-expression of progesterone

receptor.

3. Eligible for fulvestrant therapy and at least one of the following: palbociclib,

ribociclib, or abemaciclib, as per local investigator assessment. Previous tolerance

to specific CDK4/6 inhibitors and dose levels required.

4. Adequate organ and bone marrow functions.

5. Consent to provide a mandatory FFPE tumour sample.

Inclusion criteria only for phase III:

1. Previous treatment with an ET (tamoxifen, AI, or oral SERD) as a single agent or in

combination, with:

a. radiological evidence of breast cancer recurrence or progression while on, or within 12

months of, completing a (neo)adjuvant ET regimen

Key exclusion criteria for both phases:

1. History of another primary malignancy except for malignancy treated with curative

intent with no known active disease ≥ 2 years before the first dose of study

intervention and of low potential risk for recurrence.

2. Radiotherapy within 2 weeks prior to study treatment initiation.

3. Major surgery or significant traumatic injury within 4 weeks of the first dose of

study treatment.

4. Persistent toxicities (CTCAE Grade >1) caused by previous anticancer therapy,

excluding alopecia. Participants with irreversible toxicity that is not reasonably

expected to be exacerbated by study intervention may be included (eg, hearing loss or

peripheral sensory neuropathy) after consultation with the AstraZeneca study

physician.

5. Spinal cord compression, brain metastases or leptomeningeal metastases unless these

lesions are definitively treated (eg. radiotherapy, surgery) and clinically stable off

steroids for management of symptoms for at least 4 weeks prior to study treatment

initiation.

6. Any of the following cardiac criteria at screening:

(a). Mean resting corrected QT interval (QTcF): (i) Participants to be treated with

palbociclib:: QTcF ≥ 470 ms obtained from the average of 3 consecutive (triplicate)

ECGs (ii) Participants to be treated with ribociclib: QTcF ≥ 450 ms obtained from the

average of 3 consecutive (triplicate) ECGs (iii) Participants to be treated with

abemaciclib (Phase Ib only): QTcF ≥ 470 ms obtained from the average of 3 consecutive

(triplicate) ECGs (b). Any clinically important abnormalities in cardiac rhythm,

conduction or morphology of resting ECG (eg, complete left bundle branch block,

third-degree heart block) (c). Any factors that increase the risk of QTc prolongation

or risk of arrhythmic events (d). Experience of any of the following procedures or

conditions in the preceding 6 months: coronary artery bypass graft, angioplasty,

vascular stent, myocardial infarction, unstable angina pectoris, congestive heart

failure New York Heart Association (NYHA) grade ≥ 2 (e). Uncontrolled hypotension (f)

uncontrolled hypertension (g). Cardiac ejection fraction outside institutional range

of normal or < 50% (whichever is higher)

7. uncontrolled or high grade or symptomatic arrhythmia and atrial fibrillation

8. Any of these clinically significant abnormalities of glucose metabolism at screening:

1. . diabetes mellitus type I or type II requiring insulin treatment

2. . HbA1c ≥ 8.0% (63.9 mmol/mol)

9. Previous allogeneic bone marrow transplant or solid organ transplant.

Key exclusion criteria for the phase III only:

1. Any prior treatment with, AKT, PI3K or mTOR inhibitors.

2. Prior treatment with CDK4/6 inhibitors in the metastatic setting (prior CDK4/6

inhibitors permitted in the adjuvant setting provided there was a CDK4/6i treatment

free interval of at least 12 months).

3. More than 1 line of chemotherapy for metastatic disease

Studien-Rationale

Primary outcome:

1. Phase Ib: 1. The number of participants with dose-limiting toxicity, as defined in the protocol. (Time Frame - Within the first 28 day cycle.):
Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria.

2. Phase Ib: 2. The number of participants with treatment-related adverse events. (Time Frame - From baseline up to approximately 36 months.):
Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.

3. Phase Ib: 3. The number of participants with treatment-related serious adverse events. (Time Frame - From baseline up to approximately 36 months.):
Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.

4. Phase III: 1. Progression Free Survival (PFS). (Time Frame - Up to approximately 37 months.):
Progression Free Survival (PFS) is defined as time from randomization until progression per RECIST v1.1. as assessed by BICR or death due to any cause. RECIST related endpoints such as PFS, ORR, DoR, CBR will be collected

Secondary outcome:

1. Phase Ib: 1. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmax. (Time Frame - Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days).):
Maximum observed plasma (peak) drug concentration.

2. Phase Ib: 2. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-72h. (Time Frame - Cycle 0 (Cycle 0 is 3 days).):
Partial area under the plasma concentration-time curve from zero to 72 hours post-dose.

3. Phase Ib: 3. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-24h. (Time Frame - Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days).):
Partial area under the plasma concentration-time curve from zero to 24 hours post-dose.

4. Phase Ib: 4. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmin. (Time Frame - Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 0 is 3 days and Cycle 1 is 28 days).):
Minimum observed plasma drug concentration.

5. Phase Ib: 5. PK parameters for capivasertib: Cmax. (Time Frame - Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).):
Maximum observed plasma (peak) drug concentration.

6. Phase Ib: 6. PK parameters for capivasertib: AUC0-12h. (Time Frame - Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).):
Partial area under the plasma concentration-time curve from zero to 12 hours post-dose.

7. Phase Ib: 7. PK parameters for capivasertib: Cmin. (Time Frame - Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).):
Minimum observed plasma drug concentration.

8. Phase Ib: 8. Objective Response Rate (ORR). (Time Frame - Up to approximately 36 months.):
Objective Response Rate (ORR) is defined as the proportion of patients with measurable disease at baseline who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator at local site per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

9. Phase Ib: 9. Clinical Benefit Rate (CBR) at 24 weeks. (Time Frame - Up to approximately 36 months.):
Clinical Benefit Rate (CBR) 24 weeks is defined as the percentage of patients who have a CR or PR or who have SD per RECIST v1.1 as assessed by the investigator at local site for at least 23 weeks after date of first dose.

10. Phase Ib: 10. Duration of Response (DoR). (Time Frame - Up to approximately 36 months.):
Duration of Response (DoR) will be defined as the time from the date of first documented confirmed response until date of documented progression per RECIST v1.1 as assessed by the investigator at local site or death due to any cause.

11. Phase Ib: 11. Progression Free Survival (PFS). (Time Frame - Up to approximately 36 months.):
Progression Free Survival (PFS) is defined as time from date of first dose until progression per RECIST v1.1. as assessed by the investigator at local site or death due to any cause.

12. Phase III: 1. Overall Survival (OS). (Time Frame - Up to approximately 64 months.):
Overall Survival (OS) - time from randomisation until the date of death due to any cause.

13. Phase III: 2. Progression Free Survival (PFS) in PIK3CA/ AKT1/ PTEN-altered population. (Time Frame - Up to approximately 37 months.):
Progression Free Survival (PFS) - time from randomisation until progression per RECIST v 1.1 as assessed by BICR or death due to any cause.

14. Phase III: 3. Progression Free Survival 2 (PFS2). (Time Frame - Up to approximately 64 months.):
Progression Free Survival (PFS2) - time from randomisation to the earliest of the progression event, after first subsequent therapy or death.

15. Phase III: 4. Objective Response Rate (ORR). (Time Frame - Up to approximately 37 months.):
Objective Response Rate (ORR) - the proportion of patients who have a complete or partial response), as determined by BICR per RECIST v1.1.

16. Phase III: 5. Duration of Response (DoR). (Time Frame - Up to approximately 37 months.):
Duration of Response (DoR) - the time from the date of first documented response until the date of progression per RECIST v1.1 as assessed by BICR, or death due to any cause.

17. Phase III: 6. Clinical Benefit Rate (CBR) at 24 weeks. (Time Frame - Up to approximately 37 months.):
Clinical Benefit Rate (CBR) at 24 weeks-the % of patients who have a CR or PR or who have SD per RECIST v1.1 as assessed by BICR for at least 23 weeks after randomisation.

18. Phase III: 7. Participant-reported physical functioning (Time Frame - Up to approximately 64 months.):
TTD of physical functioning as measured by the physical functioning subscale of the EORTC QLQ-C30.

19. Phase III: 8. participant-reported GHS/QoL in participants (Time Frame - Up to approximately 64 months.):
TTD of GHS/QoL as measured by the GHS/QoL subscale of the EORTC QLQ-C30.

20. Phase III: 9. Participant-reported overall side effect bother in participants in the capivasertib arm relative to control arm (Time Frame - Up to approximately 64 months.):
Proportion of participants experiencing different levels of overall treatment tolerability as measured by the Patient Global Impression-Treatment Tolerability (PGI-TT).

21. Phase III: 10. Plasma concentration of capivasertib pre- and post-dose. (Time Frame - Up to approximately 64 months.):
Plasma concentration of capivasertib pre-, and post-dose.

22. Phase III: 11. The number of participants with adverse events. (Time Frame - Up to approximately 64 months.):
Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with adverse events.

23. Phase III: 12. The number of participants with serious adverse events. (Time Frame - Up to approximately 64 months.):
Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with serious adverse events.

Studien-Arme

  • Experimental: Capivasertib Plus Palbociclib and Fulvestrant
    Capivasertib Plus Palbociclib and Fulvestrant (Ph 1b)
  • Experimental: Capivasertib Plus Ribociclib and Fulvestrant
    Capivasertib Plus Ribociclib and Fulvestrant (Ph 1b)
  • Experimental: Capivasertib Plus Abemaciclib and Fulvestrant
    Capivasertib Plus Abemaciclib and Fulvestrant (Ph 1b)
  • Experimental: Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib)
    Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III)
  • Active Comparator: Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib)
    Fulvestrant and investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III)

Geprüfte Regime

  • Capivasertib:
    Phase Ib: Capivasertib 320 mg/ 400 mg administered PO BD 4 days on /3 days off per week for 4 weeks (28 days cycle) Phase III: : Capivasertib, administered PO BD 4 days on / 3 days off per week for 4 weeks (28 days cycle) at the dose confirmed in the phase Ib portion
  • Fulvestrant:
    Phase Ib and Phase III: 500 mg (2 injections of 250 mg) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter
  • Palbociclib:
    Phase Ib: 100 mg/ 125 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose of 125 mg.
  • Ribociclib:
    Phase Ib: 200 mg/ 400 mg/ 600 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose confirmed in the phase 1b portion.
  • Abemaciclib:
    Phase Ib: 50 mg/ 100 mg/ 150 mg. Twice daily for 28 consecutive days to comprise a complete 28-day cycle

Quelle: ClinicalTrials.gov


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"Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)"

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