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

NCT03227328 | Completed Phase 2

• 2 other identifiers: IRST174.192016-004107-31
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 20

Brief 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 (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.

Conditions

Hormone Receptor Positive Breast Cancer; Metastatic Breast Cancer; Hormone Receptor Negative Breast Cancer

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

Outcome Measures

Primary Outcomes (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

  up to 39 months

Secondary Outcomes (10)

• EORTC QLQ-C30 quality of life between the 2 arms

  up to 39 months

• QLQ-BR23 quality of life between the 2 arms

  up to 39 months

• toxicity

  up to 39 months

• time to treatment failure (TTF)

  up to 39 months

• best objective response rate

  up to 39 months

Study Arms (2)

Treatment Arm A

ACTIVE COMPARATOR

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

Drug: concomitant cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy

Treatment Arm B

EXPERIMENTAL

chemotherapy plus endocrine therapy (administered either concomitantly or sequentially)

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

Interventions

concomitant cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy DRUG

CDK4/6 inhibitor: * palbociclib * ribociclib * abemaciclib Endocrine therapy: * non-steroidal or steroidal AI * fulvestrant

Treatment Arm A

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

Treatment Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead
• Agenzia Italiana del Farmaco: collaborator

Study Sites (20)

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

Bologna, BO, Italy

Location

UO Oncologia Medica IRST IRCCS

Meldola, FC, 47014, Italy

Location

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

Carpi, MO, Italy

Location

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

Piacenza, PC, Italy

Location

UOC Oncologia Medica AUSL Romagna-Ravenna

Ravenna, RA, 48121, Italy

Location

UO Oncologia Medica AUSL Romagna-Rimini

Rimini, RI, Italy

Location

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

Ancona, Italy

Location

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

Bari, Italy

Location

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

Cremona, Italy

Location

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

Ferrara, Italy

Location

Ospedale Civile di Guastalla - AUSL di Reggio Emilia

Guastalla, Italy

Location

AUSL Imola

Imola, Italy

Location

Ospedale Mater Salutis - Azienda ULSS9 Scaligera

Legnago, Italy

Location

Ospedale di Macerata, ASUR AV3

Macerata, Italy

Location

A.O.U. Policlinico di Modena

Modena, Italy

Location

A.O.U. Maggiore della Carità di Novara

Novara, Italy

Location

U.O. Oncologia Medica, AOU di Parma

Parma, Italy

Location

A.O. Santa Maria della Misericordia di Perugia

Perugia, Italy

Location

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

Reggio Emilia, Italy

Location

Ospedale di Sondrio - ASST Valtellina e Alto Lario

Sondrio, Italy

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Andrea Rocca

  Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Via Maroncelli 40, 47014 Meldola, ITALY

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: group sequential response adaptive Randomized, open label, multicenter,

Study Record Dates

• First Submitted: July 19, 2017
• First Posted: July 24, 2017
• Study Start: August 2, 2017
• Primary Completion: February 1, 2022
• Study Completion: July 1, 2022
• Last Updated: November 7, 2024

Record last verified: 2024-11

Locations

IT (20)