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Hormone Receptor Positive Breast CancerPhase 2KENDONCT03227328

CDK4/6-inhibitor or Chemotherapy, in Combination with ENDOcrine Therapy, for Advanced Breast Cancer / KENDO

A Phase 2 study testing concomitant cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy and chemotherapy plus endocrine therapy (administered either concomitantly or sequentially) in people with Hormone Receptor Positive Breast Cancer and Metastatic Breast Cancer, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 20 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Prospective, open label, multicenter, group sequential response adaptive randomized phase 2 study, comparing two treatments for locally advanced or metastatic luminal breast cancer: Arm A: concomitant cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor (palbociclib, ribociclib or abemaciclib) plus endocrine therapy… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
concomitant cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy and chemotherapy plus endocrine therapy (administered either concomitantly or sequentially)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
20 sitesItaly
Study dates
2 Aug 2017to 1 Jul 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological diagnosis of HR-positive (ER ≥10% of tumor cells), HER2-negative breast cancer, determined by local laboratory on most recent available tumor tissue.
  • Locally advanced (not susceptible to locoregional therapy) or metastatic disease (herein globally defined as "advanced breast cancer (ABC)").
  • At least one of the following signs of disease aggressiveness:
  • The main criteria are a low expression of ER (10% ≤ ER < 50%) and/or a relapse while on the first 2 years of adjuvant endocrine therapy or disease progression (PD) within the first 6 months of first-line endocrine therapy for ABC
  • Other tumor characteristics of aggressiveness that make the patient potentially candidate to chemotherapy, according to the guidelines of the Italian Association of Medical Oncology [AIOM guidelines 2017], such as: elevated Ki67 (preferably documented, if available, on a metastatic biopsy), low expression of hormone receptors (e.g. progesterone receptor <20%), extended visceral involvement or visceral involvement at risk for organ failure, uncontrolled symptoms; these patients are eligible if chemotherapy is considered a suitable option by the treating physician.
  • Postmenopausal women, or premenopausal women undergoing treatment with LHRH analog, or men (either receiving treatment with LHRH analog or not).
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  • Measurable disease according to RECIST 1.1 criteria, or not measurable but evaluable disease.
  • Any prior adjuvant chemotherapy or endocrine therapy
  • No prior chemotherapy for advanced disease.
  • Up to one prior line of endocrine therapy for ABC.
  • Age ≥ 18 years.
  • Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤2 (see Appendix A).
  • Adequate organ (renal, hepatic, bone marrow, cardiac) functions.
  • Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to use effective contraception during the study period and for 4 months thereafter. Effective contraception methods include: total abstinence (when this is in line with the preferred and usual lifestyle of the subject); tubal ligation; male sterilization; combination of the placement of an intrauterine device or intrauterine system and barrier methods of contraception with spermicidal suppository.
  • Participant is willing and able to give informed consent for participation in the study.

Who cannot join

  • Any prior chemotherapy or CDK4/6 inhibitor for advanced breast cancer
  • More than 1 prior line of endocrine therapy for ABC.
  • Patients who have not recovered from adverse events due to prior therapies to grade ≤1 (excluding alopecia).
  • Active central nervous system metastases.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in the study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Prior history of non-breast malignancy (except for adequately controlled basal cell carcinoma of the skin, carcinoma in situ of the cervix, in situ carcinoma of the bladder), unless treated with curative intent and disease free for at least 3 years.

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

Italy20 sites

  • A.O.U. Ospedali Riuniti Umberto I - GM Lancisi - G Salesi

    Ancona

  • U.O. Oncologia Medica; Ist. Tumori Giovanni Paolo II - IRCCS Osp. Oncologico di Bari

    Bari

  • U.O. Oncologia Medica, P.O. Bellaria-Maggiore

    Bologna, BO

  • Dip. Medicina Interna e Riabilitazione - U.O. Medicina Interna Oncologica, Ospedale Ramazzini

    Carpi, MO

  • Terapia Molecolare e Farmaco Genomica, Azienda Socio-Sanitaria Territoriale di Cremona

    Cremona

  • A.O.U. di Ferrara Arcispedale Sant'Anna

    Ferrara

  • Ospedale Civile di Guastalla - AUSL di Reggio Emilia

    Guastalla

  • AUSL Imola

    Imola

  • Ospedale Mater Salutis - Azienda ULSS9 Scaligera

    Legnago

  • UO Oncologia Medica IRST IRCCS

    Meldola, FC, 47014

  • A.O.U. Policlinico di Modena

    Modena

  • A.O.U. Maggiore della Carità di Novara

    Novara

  • U.O. Oncologia Medica, AOU di Parma

    Parma

  • A.O. Santa Maria della Misericordia di Perugia

    Perugia

  • Dip. Oncologia-Ematologia - U.O. Oncologia Medica,Azienda USL di Piacenza - Ospedale Civile

    Piacenza, PC

  • Ospedale di Macerata, ASUR AV3

    Province of Macerata

  • UOC Oncologia Medica AUSL Romagna-Ravenna

    Ravenna, RA, 48121

  • A.O. Arcispedale S. Maria Nuova IRCCS di Reggio Emilia

    Reggio Emilia

  • UO Oncologia Medica AUSL Romagna-Rimini

    Rimini, RI

  • Ospedale di Sondrio - ASST Valtellina e Alto Lario

    Sondrio

Other trials in Italy

About this study

Official title: Group Sequential Response Adaptive Randomized Clinical Trial of Concomitant Chemotherapy Plus Endocrine Therapy Versus Cyclin-dependent Kinase 4/6 (CDK4/6) Inhibitor Plus Endocrine Therapy for Advanced Hormone Receptor-positive, HER2-negative Breast Cancer.

Prospective, open label, multicenter, group sequential response adaptive randomized phase 2 study, comparing two treatments for locally advanced or metastatic luminal breast cancer:

  • Arm A: concomitant cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor (palbociclib, ribociclib or abemaciclib) plus endocrine therapy (aromatase inhibitor [AI] or fulvestrant)
  • Arm B: chemotherapy plus endocrine therapy (AI or fulvestrant, administered either concomitantly from the beginning of chemotherapy or sequentially after 4-6 months of chemotherapy) Treatments will continue until disease progression or toxicity or patient refusal.
Read the detailed description

Group sequential response adaptive randomized clinical trial of concomitant chemotherapy plus endocrine therapy versus cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy for advanced hormone receptor-positive, HER2-negative breast cancer Primary Objective: To compare the efficacy of concomitant CDK4/6 inhibitor plus endocrine therapy versus chemotherapy plus endocrine therapy (administered either concomitantly from the beginning or sequentially) in terms of progression-free survival (PFS).

Secondary objectives: To compare between treatment arms:

  • quality of life (EORTC quality of life questionnaire(QLQ) QLQ -C30 and QLQ-BR23)
  • toxicity (CTCAE version 5.0)
  • time to treatment failure
  • best response rate
  • duration of response
  • clinical benefit rate
  • overall survival (OS)
  • PFS and clinical benefit with the subsequent line of treatment after cross-over: CDK4/6 inhibitors plus endocrine therapy in patients treated with chemotherapy plus endocrine therapy, chemotherapy (with or without endocrine therapy) in patients treated with CDK4/6 inhibitors plus endocrine therapy
  • correlative biomarkers of response to CDK4/6 inhibitors and chemotherapy:
  • tissue markers (on the primary tumor and / or metastatic tissue)
  • circulating markers (e.g. CTCs, ctDNA)

The patients will be allocated according to block randomization until two events are observed in each arm, and then according to the time-to-event adaptation of the group sequential Doubly-adaptive Biased Coin Design (DBCD) whose allocation probabilities are computed at the end of the block randomization and after around 70% and 85% of the 150 maximum patients are enrolled during a 23 month period. At these last two (i.e. after 105 and 128 patients, respectively), interim analysis on efficacy will be carried out allowing for early stopping. At the end of the 16-month follow up, administrative censoring is introduced. Therefore, the total study duration is 39 months.

Previous results on palbociclib and fulvestrant combination in second line and the characteristics of our target population lead us to assume a median PFS of 8 and 12 months for arm A and B, respectively. Under this scenario, for a sample size of at the most 150 patients, the proposed design strategy has led to a simulated power of 0.911 compared with a 0.717 one for the Complete Randomisation design.

Being tested
concomitant cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy, chemotherapy plus endocrine therapy (administered either concomitantly or sequentially)
Keywords
HR-positive Breast Cancer, metastatic breast cancer, First line treatment, endocrine therapy, chemotherapy, randomized phase III trial, aromatase inhibitor, HR-negative Breast Cancer, CDK4/6 inhibitor
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • concomitant cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor plus endocrine therapyDrug

    CDK4/6 inhibitor:

    • palbociclib
    • ribociclib
    • abemaciclib

    Endocrine therapy:

    • non-steroidal or steroidal AI
    • fulvestrant

  • chemotherapy plus endocrine therapy (administered either concomitantly or sequentially)Drug

    Standard Chemotherapy regimens will be classified as:

    • anthracycline + taxane,
    • taxane,
    • anthracycline,
    • capecitabine / fluoropyrimidines,
    • others.

    Endocrine therapy:

    • non-steroidal or steroidal AI
    • fulvestrant
Study groups in NCT03227328
Study groupRoleWhat they receive
Treatment Arm AActive comparatorconcomitant cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy
Receives: Drug: concomitant cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy
Treatment Arm BExperimentalchemotherapy plus endocrine therapy (administered either concomitantly or sequentially)
Receives: Drug: chemotherapy plus endocrine therapy (administered either concomitantly or sequentially)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS)

    time from randomization until first disease progression or death; disease progression is defined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1

    Measured: up to 39 months

Secondary outcomes (10)

  1. EORTC QLQ-C30 quality of life between the 2 arms

    evaluation of EORTC QLQ-C30 Version 3.0

    Measured: up to 39 months

  2. QLQ-BR23 quality of life between the 2 arms

    evaluation of QLQ-BR23 (breast cancer specific)

    Measured: up to 39 months

  3. toxicity

    evaluation of toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measured: up to 39 months

  4. time to treatment failure (TTF)

    the time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient refuse or death.

    Measured: up to 39 months

  5. best objective response rate

    best objective (partial or complete) response rate according to RECIST 1.1

    Measured: up to 39 months

  6. duration of response

    time from documentation of tumor response to disease progression

    Measured: up to 39 months

  7. clinical benefit rate (CBR)

    the percentage of patients who achieved complete response, partial response or stable disease lasting longer than 24 weeks

    Measured: up to 39months

  8. overall survival (OS)

    time from randomization until death for any cause

    Measured: up to 39 months

  9. Progression free survival (PFS)

    PFS and clinical benefit with the subsequent line of treatment after cross-overtime calculated from randomization until the date of start of the subsequent treatment line

    Measured: up to 39 months

  10. correlative biomarkers of response to chemotherapy and endocrine therapy

    correlative biomarkers assessed on baseline tumor specimens (from primary tumor or metastatic biopsies) and blood samples collected at baseline and at different timepoints until evidence of disease progression

    Measured: up to 39 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jul 2017
  2. Study start2 Aug 2017
  3. Primary completion1 Feb 2022
  4. Study completion1 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
group sequential response adaptive Randomized, open label, multicenter,
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03227328
Sponsor's protocol ID
IRST174.19
Other IDs
2016-004107-31, 2016
Acronym
KENDO
Status last verified
Nov 2024
First submitted
19 Jul 2017
Last updated
7 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing concomitant cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy and chemotherapy plus endocrine therapy (administered either concomitantly or sequentially) in people with Hormone Receptor Positive Breast Cancer and Metastatic Breast Cancer, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 20 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: up to 39 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03227328.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2024.

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