Implementing Geriatric Assessment for Dose Optimization of CDK 4/6-inhibitors in Older Breast Cancer Patients - a Pragmatic Randomized-controlled Trial (IMPORTANT Trial)
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Enrollment
- 495
- Locations
- 12
- Primary Endpoint
- Time to treatment failure
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 70 Years to — (Older Adult)
- Sex
- 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.
- •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.
Arms & Interventions
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.
Intervention: CDK 4/6 inhibitors (Drug)
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.
Intervention: Endocrine therapy (Drug)
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.
Intervention: CDK 4/6 inhibitors (Drug)
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.
Intervention: Endocrine therapy (Drug)
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.
Intervention: CDK 4/6 inhibitors (Drug)
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.
Intervention: Endocrine therapy (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Overall treatment utility (OTU)(Three months after treatment initiation)
- Overall survival(Up to 5 years from treatment initiation)
- Progression free survival(Up to 5 years from treatment initiation)
- Time to chemotherapy initiation(Up to 5 years from treatment initiation)
- Assessment of Quality of life(Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first)
- Frequency of adverse events(Up to 5 years from treatment initiation)
- Cost effectiveness(Up to 24 months from treatment initiation)
- Time until Quality of life deterioration(Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first)