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JOURNAL ONKOLOGIE – STUDIE
SERENA-6

Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)

Rekrutierend

NCT-Nummer:
NCT04964934

Studienbeginn:
Juni 2021

Letztes Update:
30.04.2024

Wirkstoff:
AZD9833, AZD9833 placebo, Anastrozole, Anastrozole placebo, Letrozole, Letrozole placebo, Palbociclib, Abemaciclib, Luteinizing hormone-releasing hormone (LHRH) agonist, Ribociclib

Indikation (Clinical Trials):
Disease Progression

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

Studienlocations
(3 von 289)

Research Site
53111 Bonn
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
45130 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
79110 Freiburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
56068 Koblenz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Research Site
68167 Mannheim
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
33098 Paderborn
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
40878 Ratingen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
88212 Ravensburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
72076 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
71913 Hot Springs National Park
United StatesRekrutierend» Google-Maps
Research Site
33705 Saint Petersburg
United StatesRekrutierend» Google-Maps
Research Site
60657 Chicago
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
60453 Oak Lawn
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
10469 Bronx
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
10028 New York
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
13620 Seongnam-si
Korea, Republic ofRekrutierend» Google-Maps
Research Site
463-712 Seongnam-Si
Korea, Republic ofRekrutierend» Google-Maps
Research Site
603126 Nizhny Novgorod
Russian FederationSchwebend» Google-Maps
Research Site
197758 Saint Petersburg
Russian FederationSchwebend» Google-Maps
Research Site
197758 Sankt-Peterburg
Russian FederationSchwebend» Google-Maps
Research Site
194017 St. Petersburg
Russian FederationSchwebend» Google-Maps
Research Site
08908 L'Hospitalet de Llobregat
SpainRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

Breast cancer is the most common type of cancer among women. In people with breast cancer,

the body is not able to control the growth of some cells. These extra cells can form tumors

in the breast. When tumor cells move to different parts of the body this is called advanced

cancer. Researchers are looking for better ways to treat advanced breast cancer.

This trial will look at six drugs: palbociclib, abemaciclib, ribociclib, letrozole,

anastrozole, and AZD9833. AZD9833 is the trial drug, and is the only drug not yet approved

for use. Palbociclib, abemaciclib and ribociclib work in the same way and are a type of

cancer drug called a CDK4/6 inhibitor. Letrozole and anastrozole work in the same way and are

both a type of cancer drug called an aromatase inhibitor (AI). CDK4/6 inhibitors and AIs work

together to block the tumor's ability to grow. These drugs have been approved for combined

use in people with advanced breast cancer that is HR-positive and HER2-negative. But if

people get mutations in the ESR1 gene, it can make the AI and CDK4/6 inhibitor treatment work

less well.

The trial drug, AZD9833, is designed to work with a CDK4/6 inhibitor in the same way that an

AI does. Researchers think that AZD9833 might work better with a CDK4/6 inhibitor than an AI

does in people who get mutations in their ESR1 gene.

Participants in this trial will have already been receiving one of the following combinations

of a CDK4/6 inhibitor and an AI:

- palbociclib + anastrozole

- palbociclib + letrozole

- abemaciclib + anastrozole

- abemaciclib + letrozole

- ribociclib + anastrozole

- ribociclib + letrozole

During the trial, participants will remain on the same CDK4/6 inhibitor that they were taking

before the trial.

In this trial, the researchers want to find out how well switching a participant with an ESR1

gene mutation from an AI (letrozole or anastrozole) to AZD9833 works in the treatment of

advanced breast cancer that is HR-positive and HER2-negative.

The researchers will look at which trial treatment helps the participants live longer with

the cancer before it gets worse.

The researchers also want to know more about how safe AZD9833 is.

The trial participants will be split into 2 groups:

- Participants in Group A will receive AZD9833, a CDK4/6 inhibitor, and a placebo

- Participants in Group B will receive an AI, a CDK4/6 inhibitor, and a placebo

A placebo looks like a treatment but does not have any medicine in it.

A computer program will be used to randomly choose the treatments each participant gets. This

helps make sure the groups are chosen fairly. Researchers do this so that comparing the

results of each treatment will be as accurate as possible.

The participants will take their trial treatments over 28-day cycles, with a placebo and

either AZD9833 or an AI taken once daily by mouth for all 28 days. If the participant is

taking abemaciclib, they will take it twice daily by mouth for all 28 days. If the

participant is taking palbociclib or ribociclib, they will take it once daily by mouth for 21

days and then stop taking it for the final 7 days of the cycle. The participant will then

repeat the 28-day cycle receiving the trial treatment in the same way for as long as they are

in the trial.

Participants will visit their trial site regularly throughout the trial. At these visits, the

trial doctors will check the health of the participants. They will also take blood samples

and do scans of the participants' tumors.

Participants will take their trial treatment until their cancer gets worse or they decide to

leave the trial.

*Palbociclib and Abemacliclib cohorts are currently ongoing. Ribociclib cohort will be open

pending on availability of the data.

Ein-/Ausschlusskriterien

INCLUSION CRITERIA:

INFORMATION FOR TRIAL PARTICIPANTS - Participants can join the trial if they:

- Have advanced breast cancer that is not able to be treated with surgery or radiation;

- Have an ESR1 mutation in their cancer;

- Have breast cancer that is HR-positive and HER2-negative;

- Are currently being treated with a CDK4/6 inhibitor and an AI and have been taking

these drugs for at least 6 months;

- Have not had their cancer get worse after taking an AI and CDK4/6 inhibitor;

- Are able to do their daily activities;

- Are at least 18.

Full list of inclusion criteria:

- Proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally

recurrent or metastatic disease not amenable to resection or radiation therapy with

curative intent;

- Documentation of histologically confirmed diagnosis of estrogen receptor positive

(ER+) /HER2- breast cancer based on local laboratory results;

- Currently on AI (letrozole or anastrozole) + CDK4/6 inhibitor (palbociclib,

abemaciclib or ribociclib) ± LHRH as the initial endocrine based treatment for

advanced disease;

- Eastern Cooperative Oncology Group performance status of 0 or 1;

- ESR1m detected by central testing of ctDNA;

- Willingness and ability to comply with scheduled visits, treatment plan, laboratory

tests, and other study procedures;

- Adequate organ and marrow function.

EXCLUSION CRITERIA:

INFORMATION FOR TRIAL PARTICIPANTS - Participants cannot join the trial if they:

- Had certain types of tumors in the past that may come back;

- Are currently taking any other treatments for their cancer or other conditions

including hormone replacements, medications, or supplements that could interfere with

the trial treatment;

- Have or have had any major health problem, infection, or recent surgery that could

make it difficult or dangerous to participate in this trial.

Full list of exclusion criteria:

- Advanced, symptomatic, visceral spread, that are at risk of life-threatening

complications in the short term;

- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or

leptomeningeal disease;

- Any evidence of severe or uncontrolled systemic diseases which, in the investigator's

opinion, makes it undesirable for the participant to participate in the study or that

would jeopardize compliance with the protocol;

- Patient with known or family history of severe heart disease;

- Previous treatment with AZD9833, investigational SERDs or fulvestrant;

- Currently pregnant (confirmed with positive pregnancy test) or breastfeeding;

- Persistent non-haematological toxicities (CTCAE Grade > 2) caused by CDK4/6 inhibitor

and/or AI treatment.

Studien-Rationale

Primary outcome:

1. Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST version 1.1) (Time Frame - From randomization until the earlier of the progression event or death (approximately 2 years)):
PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST 1.1) or death.



Secondary outcome:

1. Progression-free survival 2 (PFS2) (Time Frame - From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (approximately 3.5 years)):
PFS2 is defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.

2. Overall survival (OS) (Time Frame - From randomization until the date of death due to any cause (approximately 5 years)):
The OS is defined as the time from randomization to death due to any cause.

3. Chemotherapy free survival (Time Frame - From randomization until the earlier of the start date of chemotherapy or death due to any cause (approximately 5 years)):
Time to chemotherapy is defined as the time from randomization until the earlier of the start date of chemotherapy or death due to any cause.

4. Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1 (Time Frame - From randomization until a response or in the absence of a response from randomization up until progression, or the last evaluable assessment in the absence of progression (approximately 5 years)):
ORR is defined as the proportion of patients who have a complete response (CR) or partial response (PR), as determined by the investigator at local site per RECIST 1.1.

5. Clinical benefit rate at 24 weeks (CBR24) (Time Frame - At least 23 weeks after randomisation for each patient (1 week window for RECIST assessment)):
CBR at 24 weeks is defined as the percentage of participants who have a complete response (CR) or partial response or who have stable disease (SD) per RECIST 1.1 as assessed by the investigator at local site for At least 23 weeks after randomisation for each patient to allow for an early assessment within the assessment window (1 week window for RECIST assessment)

6. Change from baseline in EORTC QLQ-C30 scale scores (Time Frame - From baseline until second progression (approximately 5 years)):
Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.

7. Change from baseline in EORTC QLQ-BR23 scale scores (Time Frame - From baseline until second progression (approximately 5 years)):
Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Scale scores range from 0-100. For functioning scales, higher scores indicate better functioning. For symptom scales, higher scores indicate greater symptom burden.

8. Plasma concentration of AZD9833 at specified timepoints (Time Frame - on Day 15 for each patient):
To assess the steady state PK of AZD9833 in combination with palbociclib or abemaciclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration.

Studien-Arme

  • Experimental: AZD9833 + palbociclib, abemaciclib or ribociclib
    The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily)
  • Active Comparator: Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib
    The patients will recieve anastrozole (1 mg, PO, once daily) or letrozole (2.5 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)

Geprüfte Regime

  • AZD9833:
    Dosage formulation: AZD9833 tablets will be administered orally
  • AZD9833 Placebo:
    Dosage formulation: AZD9833 placebo tablets will be administrated orally.
  • Anastrozole:
    Dosage formulation: anastrozole tablets will be administered orally.
  • Anastrozole placebo:
    Dosage formulation: anastrozole placebo tablets will be administrated orally.
  • Letrozole:
    Dosage formulation: letrozole tablets will be administered orally.
  • Letrozole placebo:
    Dosage formulation: letrozole placebo tablets will be administered orally.
  • Palbociclib:
    Dosage formulation: palbociclib tablets/capsules will be administered orally
  • Abemaciclib:
    Dosage formulation: abemaciclib tablets will be administered orally
  • Luteinizing hormone-releasing hormone (LHRH) agonist:
    Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.
  • Ribociclib:
    Dosage formulation: ribociclib tablets will be administered orally

Quelle: ClinicalTrials.gov


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