Implementing Geriatric Assessment for Dose Optimization of Cyclin-dependent Kinase (CDK) 4/6-inhibitors in Older Breast Cancer Patients (IMPORTANT)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT06044623 |
Recruitment Status :
Recruiting
First Posted : September 21, 2023
Last Update Posted : April 11, 2024
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
IMPORTANT study is a multicenter, open-label, prospective, randomized-controlled, non-inferiority trial with a pragmatic approach involving older patients (≥ 70 years old) with advanced hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, not amenable for curative treatment and without prior therapy for advanced disease, who are suitable to receive CDK 4/6-inhibitors plus endocrine therapy as first line therapy. The study implements two approaches with high level of evidence, namely the use of comprehensive geriatric assessment (CGA) approach in treatment decision making and the use of CDK 4/6-inhibitors as the initial treatment of choice, to investigate whether a common clinical practice (starting dose reduction of CDK 4/6-inhibitors in older patients) with evidence of low certainty can be standardized using a more individualized-based approach.
On the basis of baseline CGA assessment, patients will either receive full dose of CDK 4/6-inhibitors plus endocrine therapy (if patients are fit according to CGA) or be randomized to full dose vs. reduced initial dose of CDK 4/6-inhibitors (if vulnerable or frail according to CGA). The study hypothesis is that adjusting the dose according to vulnerability will allow patients to tolerate treatment better without jeopardizing the treatment efficacy.
This project has received funding from the European Union's HORIZON 2022 research and innovation actions supporting the implementation of the Mission on Cancer under grant agreement No 101104589.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Metastatic Breast Cancer Advanced Breast Cancer Quality of Life Toxicity Older Patients | Drug: CDK 4/6 inhibitors Drug: Endocrine therapy | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 495 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Implementing Geriatric Assessment for Dose Optimization of CDK 4/6-inhibitors in Older Breast Cancer Patients - a Pragmatic Randomized-controlled Trial (IMPORTANT Trial) |
Actual Study Start Date : | March 4, 2024 |
Estimated Primary Completion Date : | April 2028 |
Estimated Study Completion Date : | April 2031 |
Arm | Intervention/treatment |
---|---|
Experimental: Lower initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)
-1 level dose reduction as initial dose of either one of the CDK 4/6-inhibitors: Palbociclib 100 mg x 1 for 21 days with 7 days off; or Ribociclib 400 mg x 1 for 21 days with 7 days off; or Abemaciclib 100 mg x 2 daily added to endocrine therapy.
|
Drug: CDK 4/6 inhibitors
Either Palbociclib, Ribociclib or Abemaciclib Drug: Endocrine therapy Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor |
Active Comparator: Full initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)
Full initial dose of either one of the CDK 4/6-inhibitors: Palbociclib 125 mg x 1 for 21 days with 7 days off; or Ribociclib 600 mg x 1 for 21 days with 7 days off; or Abemaciclib 150 mg x 2 daily) added to physician's choice endocrine therapy.
|
Drug: CDK 4/6 inhibitors
Either Palbociclib, Ribociclib or Abemaciclib Drug: Endocrine therapy Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor |
Full initial dose of CDK 4/6-inhibitor (fit patient cohort)
Full initial dose of either one of the CDK 4/6-inhibitors: Palbociclib 125 mg x 1 for 21 days with 7 days off; or Ribociclib 600 mg x 1 for 21 days with 7 days off; or Abemaciclib 150 mg x 2 daily) added to physician's choice endocrine therapy.
|
Drug: CDK 4/6 inhibitors
Either Palbociclib, Ribociclib or Abemaciclib Drug: Endocrine therapy Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor |
- Time to treatment failure [ Time Frame: Up to 5 years from treatment initiation ]The time from randomization to treatment discontinuation because of any reason including disease progression, treatment toxicity, or death due to any cause.
- Overall treatment utility (OTU) [ Time Frame: Three months after treatment initiation ]A composite endpoint that will be assessed at the first efficacy evaluation. OTU incorporates objective and participant-reported outcome measures of anticancer efficacy, tolerability and acceptability of treatment providing a simple "good, intermediate or poor" categorization of outcome.
- Overall survival [ Time Frame: Up to 5 years from treatment initiation ]The time from randomization to death from any cause.
- Progression free survival [ Time Frame: Up to 5 years from treatment initiation ]The time from randomization to first documented evidence of disease progression or death from any cause.
- Time to chemotherapy initiation [ Time Frame: Up to 5 years from treatment initiation ]The time from randomization until the initiation of chemotherapy at any treatment line after CDK 4/6-inhibitors.
- Frequency of adverse events [ Time Frame: Up to 5 years from treatment initiation ]Adverse events will be assessed based on adverse events, as graded by CTCAE v 5.0 before each cycle and up to 28 days after the end of CDK 4/6-inhibitors.
- Assessment of Quality of life [ Time Frame: Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first ]Quality of life will be assessed using three validated questionnaires, EORTC Quality of Life Questionnaire (QLQ)-C30, Elderly (ELD)-14, and European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L).
- Time until Quality of life deterioration [ Time Frame: Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first ]QoL deterioration, defined as the time from randomization until any clinically meaningful worsening (using minimal important differences as cut-off) of any QoL aspect measured by the questionnaires.
- Cost effectiveness [ Time Frame: Up to 24 months from treatment initiation ]Resource use, length of life and quality of life data will be collected during the trial for the purpose of conducting an economic evaluation.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 70 Years and older (Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
The following inclusion criteria will be applied:
- Patients male or female aged at least 70 years old at the time of informed consent.
- Histologically or cytologically confirmed diagnosis of HR-positive (defined as estrogen-receptor ≥ 1%), HER2-negative breast cancer according to analysis of the most recent tumor specimen by local laboratory.
- Advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative treatment.
- No prior systemic treatment for advanced disease (recurrence during neo-/adjuvant endocrine therapy is allowed). A prior period of treatment with aromatase inhibitors or fulvestrant for up to 28 days from the CDK 4/6-inhibitor initiation is allowed.
- Adjuvant treatment with CDK 4/6-inhibitors is allowed provided a disease-free interval from treatment end >12 months.
- Either measurable disease or non-measurable bone only disease, but evaluable according to RECIST criteria 1.1.
- Written informed consent prior to any study-specific procedures.
- Adequate organ function as defined in the summary of product characteristics (SmPC) for the CDK 4/6-inhibitors that is planned to be used.
- Able to swallow capsules.
- Able to understand and consent in English language or in native language for each participating country.
Exclusion Criteria:
Eligible patients will be excluded if they have one of the following criteria:
- Patients considered from treating physician as non-suitable for treatment with CDK 4/6-inhibitors.
- Contraindications according to SmPC for the CDK 4/6-inhibitors that is planned to be used.
- Presence of visceral crisis, lymphangitis carcinomatosis, or leptomeningeal carcinomatosis.
- History of any other cancer (except of non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years.
- Participating in other interventional trial.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06044623
Contact: Antonios Valachis, Assoc Prof | +46196021792 | important@oru.se |
Finland | |
Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki | Recruiting |
Helsinki, Finland | |
Contact: Peeter Karihtala, Prof peeter.karihtala@hus.fi | |
Greece | |
Fourth Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital | Not yet recruiting |
Athens, Greece | |
Contact: Helena Linardou, Dr elinardou@otenet.gr | |
Second Department of Medical Oncology, Hygeia Hospital | Not yet recruiting |
Athens, Greece | |
Contact: Paris Kosmidis, Dr parkosmi@otenet.gr | |
Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School | Not yet recruiting |
Patras, Greece | |
Contact: Angelos Koutras, Prof angkoutr@otenet.gr | |
Medical Oncology Unit, S. Andrew Hospital | Not yet recruiting |
Patras, Greece | |
Contact: Athina Christopoulou, Dr athinachristo@hotmail.com | |
Second Department of Medical Oncology, Euromedica General Clinic | Not yet recruiting |
Thessaloníki, Greece | |
Contact: Elena Fountzila, Assoc Prof elenafou@gmail.com | |
Italy | |
Radiation Oncology Unit - Oncology Department, Azienda Ospedaliero Universitaria Careggi | Not yet recruiting |
Florence, Italy | |
Contact: Icro Meattini, Assoc Prof icro.meattini@unifi.it | |
Contact: Luca Visani, Dr l.visani88@gmail.com | |
"Sandro Pitigliani" Department of Medical Oncology, Hospital of Prato | Not yet recruiting |
Prato, Italy | |
Contact: Laura Biganzoli, Prof laura.biganzoli@uslcentro.toscana.it | |
Contact: Emanuela Risi, Dr emanuela.risi@uslcentro.toscana.it | |
Norway | |
Department of Oncology, Akershus University Hospital (AHUS) | Not yet recruiting |
Oslo, Norway | |
Contact: Jürgen Geisler, Prof jurgen.geisler@medisin.uio.no | |
Contact: Kamilla Fjermeros, Dr Kamilla.Fjermeros@ahus.no | |
Spain | |
Department of Medical Oncology, Hospital Clinic of Barcelona | Not yet recruiting |
Barcelona, Spain | |
Contact: Raquel Gomez, Dr ragomez@recerca.clinic.cat | |
Contact: Montserrat Munoz, Dr mmunoz@clinic.cat | |
Sweden | |
Department of Oncology, Uppsala University Hospital | Not yet recruiting |
Uppsala, Sweden, 75185 | |
Contact: Hendrik Lindman, Assoc Prof Henrik.lindman@igp.uu.se | |
Contact: Aglaia Schiza, Dr Aglaia.schiza@igp.uu.se | |
Department of Oncology, Örebro University Hospital | Recruiting |
Örebro, Sweden | |
Contact: Antonios Valachis, Assoc Prof antonios.valachis@oru.se |
Study Chair: | Antonios Valachis, Assoc Prof | Region Örebro Län |
Responsible Party: | Region Örebro County |
ClinicalTrials.gov Identifier: | NCT06044623 |
Other Study ID Numbers: |
280232 |
First Posted: | September 21, 2023 Key Record Dates |
Last Update Posted: | April 11, 2024 |
Last Verified: | April 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | Yes |
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases |