Trial Title:
TRADE: Dose Escalation Tolerability of Abemaciclib in HR+ HER2- Early Stage Breast Cancer
NCT ID:
NCT06001762
Condition:
Breast Cancer
Early-stage Breast Cancer
High Risk Breast Carcinoma
Conditions: Official terms:
Breast Neoplasms
Tamoxifen
Letrozole
Anastrozole
Exemestane
Conditions: Keywords:
Breast Cancer
Early-stage high-risk breast cancer
Early-stage breast cancer
High risk breast carcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Abemaciclib
Description:
CDK4 and CDK6 inhibitor, tablet taken orally
Arm group label:
Abemaciclib
Intervention type:
Drug
Intervention name:
Tamoxifen
Description:
Selective estrogen receptor modulator, taken orally per institutional standard of care
Arm group label:
Abemaciclib
Intervention type:
Drug
Intervention name:
Anastrozole
Description:
Non-steroidal aromatase inhibitor, taken orally per institutional standard of care
Arm group label:
Abemaciclib
Intervention type:
Drug
Intervention name:
Letrozole
Description:
Non-steroidal aromatase inhibitor, taken orally per institutional standard of care
Arm group label:
Abemaciclib
Intervention type:
Drug
Intervention name:
Exemestane
Description:
Steroidal aromatase inhibitor, taken orally per institutional standard of care
Arm group label:
Abemaciclib
Intervention type:
Drug
Intervention name:
LHRH Agonist
Description:
Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard
of care
Arm group label:
Abemaciclib
Summary:
In this research study, investigators are testing if a dose-increasing strategy for
abemaciclib will have less side effects and be better tolerated than the standard dosage
of abemaciclib for participants with early-stage high-risk hormone receptor positive
breast cancer.
The names of the study drugs involved in this study are:
- Abemaciclib (CDK4 and CDK6 inhibitor)
- Tamoxifen (Selective estrogen receptor modulator)
- Anastrozole/Letrozole (Non-steroidal aromatase inhibitors)
- Exemestane (steroidal aromatase inhibitor)
- LHRH (Gonadotropin-releasing hormone agonist, or Luteinizing hormone-releasing
hormone agonist)
Detailed description:
This research study is a prospective, single-arm, open label, phase 2 study designed to
evaluate if a dose-increasing strategy for abemaciclib will have less side effects and be
better tolerated than the standard dosage of abemaciclib for participants with
early-stage high-risk hormone receptor positive breast cancer.
This research study involves adjuvant abemaciclib plus endocrine (anti-hormone) therapy
that works to target breast cancer. Adjuvant therapy is treatment given after surgery,
chemotherapy, and/or radiation therapy.
The U.S. Food and Drug Administration (FDA) has approved abemaciclib as a treatment
option for early-stage high-risk hormone receptor breast cancer. The FDA has also
approved hormonal therapies as treatment for hormone receptor positive breast cancer.
The research study procedures include screening for eligibility, study treatment
including laboratory evaluations and questionnaires, blood tests, tumor biopsies, and
stool collections.
Participation in this research study is expected to last for at least 2 years and up to 5
years.
It is expected that about 90 people will take part in this research study.
Eli Lilly and Company is supporting this study by providing funding for the study and
supplying the study drug, abemaciclib.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Stage II or III node-positive HR+/HER2- breast cancer per local laboratory
assessment.
- Eligible participants must be appropriate candidates for adjuvant abemaciclib, per
assessment of their treating physician.
- Participants must be candidates for adjuvant endocrine therapy, which may have
started before or at time of entry onto the trial. Patient may be receiving adjuvant
aromatase inhibitor or tamoxifen, +/- ovarian suppression.
- Participants must have undergone definitive surgery of the primary breast tumor(s)
within 16 months of study entry.
- At least 21 days must have elapsed between last dose of chemotherapy and
registration. Participants who previously received chemotherapy must have recovered
(Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute
effects of chemotherapy except for residual alopecia or Grade 2 peripheral
neuropathy prior to randomization.
- At least 14 days must have elapsed between end of radiotherapy and day 1 of
treatment with abemaciclib. Participants who received prior radiotherapy must have
completed and fully recovered from the acute effects of radiotherapy. No
radiotherapy should be planned to occur during study therapy.
- At least 14 days must have elapsed since most recent breast surgery prior to
registration and patient has recovered from side effects of prior surgery.
- Bilateral or multifocal/multicentric breast cancers that meet eligibility criteria
are allowed.
- ECOG performance status 0-1
- Men and women with any menopausal status ≥18 years of age
- Adequate organ function as defined below:
- Absolute neutrophil count (ANC) ≥ 1500 x 10^9/L
- Platelets ≥ 100 x 10^9/L
- Hemoglobin ≥ 8g/dL; patients may receive erythrocyte transfusions to achieve
this hemoglobin level at the discretion of the investigator. Initial treatment
must not begin earlier than the day after the erythrocyte transfusion.
- Bilirubin ≤ 1.5 x ULN. For patients with Gilbert syndrome, the limit is ≤ 2 x
institutional ULN AND direct bilirubin within the normal range of normality.
- AST/ALT ≤ 3 x institutional ULN
- Premenopausal women must have a negative serum or urine pregnancy test. Pregnancy
testing does not need to be pursued in female patients who are:
- Age > 60 years; or
- Age < 60 with intact uterus and amenorrhea for 12 consecutive months or more
AND FSH/estradiol levels within postmenopausal range; or
- Status-post bilateral oophorectomy, total hysterectomy, or bilateral tubal
ligation.
- Women of child-bearing potential and men with partners of childbearing potential
must be willing to employ one highly effective form of nonhormonal contraception
(with the exception of hormonal IUDs) or two effective forms of nonhormonal
contraception by the patient and/or partner and continue its use for the duration of
the study treatment and for 3 months after the last dose of abemaciclib.
- Subject must be able to swallow and retain oral medication.
- Ability to understand and the willingness to sign a written informed consent
document.
- Non-English-speaking patients are eligible but will be exempt from patient-completed
questionnaires.
Exclusion Criteria:
- Prior treatment with any CDK4/6 inhibitor.
- Patients with node-negative breast cancer are not eligible for the trial.
- Concurrent therapy with other investigational agents.
- Diagnosis of inflammatory breast cancer (T4d).
- History of allergic reactions attributed to abemaciclib or similar chemical or
biologic composition or excipients.
- Participants with a history of malignancy are ineligible except in the following
circumstances:
--Individuals with a history of invasive breast cancer are not eligible unless they
have been disease-free for a minimum of five years.
- Individuals with a malignancy history other than invasive breast cancer are eligible
if they have no active malignancy and are deemed by the investigator to be at low
risk for recurrence of that malignancy.
- Individuals with the following cancer history are eligible: adequately treated non-
melanoma skin cancers, curatively treated in situ cancer of the cervix, ductal
carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma. Other
exceptions may exist following review with the sponsor-investigator
- Serious and/or uncontrolled preexisting medical condition(s) that, in the judgment
of the investigator, would preclude participation in this study (for example,
interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy,
severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of
major surgical resection involving the stomach or small bowel, or preexisting
uncontrolled Crohn's disease or ulcerative colitis or a preexisting chronic
condition resulting in baseline Grade 2 or higher diarrhea) or other conditions that
in the opinion of the investigator limit compliance with study requirements.
- History of any of the following conditions: syncope of cardiovascular etiology,
ventricular arrhythmia of pathological origin (including, but not limited to,
ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
- Any of the following due to teratogenic potential of the study drugs:
- Pregnant women
- Nursing women
- Women of childbearing potential who are unwilling to employ adequate
contraception (condoms, diaphragms, IUDS, surgical sterilization, abstinence,
etc). Hormonal birth control methods are not permitted.
- Men who are unwilling to employ adequate contraception (condoms, surgical
sterilization, abstinence, etc).
- Receipt of an experimental treatment in a clinical trial within the last 30 days or
5 half-lives, whichever is longer, prior to enrollment, or is currently enrolled in
any other type of medical research (for example: medical device) judged by the
sponsor-investigator not to be scientifically or medically compatible with this
study.
- Active systemic bacterial infection (requiring intravenous [IV] antibiotics at time
of initiating study treatment) or invasive/ systemic fungal infection\
- For patients with known HIV infection, CD4 baseline count should be evaluated:
patients with a CDK count ≥ 350 cells/uL can be enrolled. Participants should be on
established anti-retroviral therapy (ART) for at least four weeks and have an HIV
viral load less than 400 copies/mL prior to enrollment. Potential pharmacological
interactions of the ART with abemaciclib and endocrine therapy must be reviewed,
particularly for the effects on CYP3A4.
- Patients with active or chronic Hepatitis B or C are eligible provided they meet
liver function laboratory criteria and cannot be on any medication with a known
interaction with the study agents.
- Participants receiving any medications or substances that are strong inhibitors or
inducers of CYP3A4, including selected herbals (e.g., hypericum) and food (e.g.,
grapefruit) known for pharmacological interactions, cannot be enrolled, due to
interference with the dose-escalation, unless the food or supplement has been
discontinued at least after an interval equivalent to 3-5 half-lives of the
inhibitor.
Gender:
Female
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Stamford Hospital
Address:
City:
Stamford
Zip:
06904
Country:
United States
Facility:
Name:
Eastern Maine Medical Center (Northern Light)
Address:
City:
Brewer
Zip:
04412
Country:
United States
Facility:
Name:
New England Cancer Specialists
Address:
City:
Scarborough
Zip:
04074
Country:
United States
Facility:
Name:
Boston Medical Center
Address:
City:
Boston
Zip:
02118
Country:
United States
Facility:
Name:
Beth Israel Deaconess Medical Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Facility:
Name:
Dana-Farber Cancer Institute at Steward St. Elizabeth's
Address:
City:
Brighton
Zip:
02135
Country:
United States
Facility:
Name:
Dana-Farber Cancer Institute at Foxborough
Address:
City:
Foxborough
Zip:
02035
Country:
United States
Facility:
Name:
Dana-Farber Cancer Institute at Merrimack Valley
Address:
City:
Methuen
Zip:
01844
Country:
United States
Facility:
Name:
Dana-Farber Cancer Institute at Milford
Address:
City:
Milford
Zip:
01757
Country:
United States
Facility:
Name:
Dana-Farber Cancer Institute at South Shore
Address:
City:
South Weymouth
Zip:
02190
Country:
United States
Facility:
Name:
Dana-Farber Cancer Insitute at Londonderry Hospital
Address:
City:
Londonderry
Zip:
03053
Country:
United States
Start date:
October 5, 2023
Completion date:
January 1, 2027
Lead sponsor:
Agency:
Dana-Farber Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Eli Lilly and Company
Agency class:
Industry
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06001762
