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ABemaciclib, ET ± paclItaxel in aGgressive HR+/HER2- MBC trIaL (ABIGAIL)

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: NCT04603183
Recruitment Status : Recruiting
First Posted : October 26, 2020
Last Update Posted : July 13, 2022
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
MedSIR

Brief Summary:
This is a multicenter, randomized, 2 arm, open label, phase II study. It is designed to compare the efficacy and safety of abemaciclib combined with ET (letrozole or fulvestrant) versus a short course with induction chemotherapy with paclitaxel followed by maintenance therapy with abemaciclib combined with ET (letrozole or fulvestrant) in patients with previously untreated, unresectable locally advanced, or metastatic HR positive/HER2 negative breast cancer with aggressive disease criteria.

Condition or disease Intervention/treatment Phase
Breast Cancer Metastatic Drug: Abemaciclib Drug: Paclitaxel Drug: Letrozole Drug: Fulvestrant Phase 2

Detailed Description:
The ABIGAIL study aims to provide consistent evidence that the combination of abemaciclib with ET -consisting of letrozole or fulvestrant-as first-line regimen is non-inferior to the optimal first-line chemotherapy -consisting of weekly paclitaxel-in terms of early ORR after the first 12 weeks of treatment in patients with HR-positive/HER2-negative ABC and at least one feature of aggressive disease associated with poor prognosis.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, 2-Arm, Open-Label, Ph-II Study of Abemaciclib Combined With ET w/ or w/o CT With Paclitaxel as 1L in Patients With Unresectable Locally Advanced or Metastatic HR(+)/HER2(-) BC With Aggressive Disease Criteria
Actual Study Start Date : June 2, 2021
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Interventional Arm (Arm A)
Abemaciclib 150 mg orally twice daily (BID) during each 28 day cycle combined with ET (2.5 mg letrozole, orally administered and taken daily during each 28-day cycle, or 500 mg fulvestrant, by intramuscular [IM] administration on Days 1 and 15 (±3 days) of the first treatment cycle and Day 1 of each cycle thereafter.
Drug: Abemaciclib
Patients will receive abemaciclib 150 mg orally twice daily (BID) (300 mg daily, administered as six 50 mg tablets) during each 28 day cycle combined with either letrozole or fulvestrant.
Other Name: Verzenios

Drug: Letrozole
Patients will receive 2.5 mg letrozole, orally administered and taken daily during each 28-day cycle combined with abemaciclib.

Drug: Fulvestrant
Patients will receive 500 mg fulvestrant, by intramuscular [IM] administration on Days 1 and 15 (±3 days) of the first treatment cycle and Day 1 of each cycle thereafter combined with abemaciclib.

Active Comparator: Control Arm (Arm B)
Paclitaxel 90 mg/m² infused over 1 hour on Days 1, 8, and 15 of the 28 day cycle, with at least a 6-day time span between separated doses.
Drug: Paclitaxel
Paclitaxel 90 mg/m² infused over 1 hour on Days 1, 8, and 15 of the 28 day cycle, with at least a 6-day time span between separated doses.
Other Name: Paclitaxel Teva




Primary Outcome Measures :
  1. 12-week overall response rate (ORR) [ Time Frame: 12 weeks ]
    Complete response (CR) or partial response (PR), during the first 12 weeks of treatment as per blinded independent central review, using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.


Secondary Outcome Measures :
  1. ORR [ Time Frame: Baseline up to 24 months ]
    The best overall response of CR or PR, as per investigator assessment and per blinded independent central review, using RECIST v 1.1.

  2. Clinical benefit rate (CBR) [ Time Frame: Baseline up to 24 months ]
    An objective response (CR or PR), or stable disease for at least 24 weeks, as per investigator assessment and blinded independent central review using RECIST v 1.1.

  3. 12-week progression-free survival (PFS) rate [ Time Frame: Baseline up to 12 weeks ]
    The proportion of patients with disease progression or death from any cause, whichever occurs first during the first 12 weeks from randomization, as per investigator assessment and blinded independent central review using RECIST v 1.1.

  4. PFS [ Time Frame: Baseline up to 24 months ]
    The period of time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, as per investigator assessment and blinded independent central review using RECIST v 1.1.

  5. Time to response (TTR) [ Time Frame: Baseline up to 24 months ]
    The time from randomization to time of the first objective tumor response (tumor shrinkage of ≥30%) observed in patients who achieved a CR or PR, as per investigator assessment and blinded independent central review using RECIST v 1.1.

  6. Duration of response (DoR) [ Time Frame: Baseline up to 24 months ]
    The time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as per investigator assessment and per blinded independent central review using RECIST v 1.1.

  7. Overall survival (OS) [ Time Frame: Baseline up to 24 months ]
    The time from randomization to death from any cause, as per investigator assessment and blinded independent central review using RECIST v 1.1.

  8. Maximum tumor shrinkage (MTS) [ Time Frame: Baseline up to 24 months ]
    The biggest decrease, or smallest increase if no decrease will be observed, as per investigator assessment and blinded independent central review using RECIST v 1.1.

  9. Time to first subsequent therapy (TFST) [ Time Frame: Baseline up to 24 months ]
    The time from randomization to the time a patient starts his/her first line treatment (first subsequent therapy).

  10. Time to second subsequent therapy (TSST) [ Time Frame: Baseline up to 24 months ]
    The time from randomization to the time a patient starts his/her second line treatment (second subsequent therapy).

  11. Time to first chemotherapy (TFC) [ Time Frame: Baseline up to 24 months ]
    The time from randomization to the time a patient included in Arm A starts his/her first line chemotherapy.

  12. Incidence of adverse events (AEs) [ Time Frame: Baseline up to 24 months ]
    Number of patients with treatment-related AEs (Grade 3 and 4 AEs and serious adverse events [SAEs]) by using the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent form (ICF) prior to participation in any study-related activities.
  2. Male or female patients ≥18 years at the time of signing the ICF.
  3. Eastern Cooperative Oncology Group performance status of 0 or 1.
  4. Life expectancy of at least 24 weeks.
  5. Pre menopausal or peri menopausal women who are being treated with a luteinizing hormone-releasing hormone analog for at least 28 days prior to study entry (if shorter, post-menopausal levels of serum estradiol/follicle-stimulating hormone [FSH] must be confirmed analytically) or post menopausal women as defined by any of the following criteria:

    1. Documented bilateral oophorectomy;
    2. Age ≥60 years;
    3. Age <60 years and cessation of regular menses for ≥12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and/or FSH level within the laboratory's reference range for post-menopausal females.
  6. Unresectable locally advanced or MBC that is not amenable to resection with curative intent.
  7. At least one of the following aggressive disease criteria:

    1. Presence of visceral disease;
    2. Either radiological as per RECIST v1.1 or clinical evidence of progressive disease (PD) on or within 36 months of completing adjuvant ET;
    3. High histological grade and/or PgR-negative status on primary tumor;
    4. Lactate dehydrogenase (LDH) >1.5 × the upper limit of normal (ULN).
  8. Histologically confirmed estrogen receptor and/or progesterone receptor (PgR) positive (with ≥1% positive stained cells according to National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines) and HER2 negative (0 to 1+ by immunohistochemistry or 2+ and negative by in situ hybridization test) breast cancer based on local testing on the most recent analyzed biopsy.
  9. Measurable disease as per RECIST v 1.1 with at least one site of disease amenable to biopsy. Patients with bone lesions as the only sites of metastatic disease are not eligible, except for patients with identifiable soft tissue components, evaluable by cross sectional imaging techniques such as CT or magnetic resonance imaging (MRI), and that meet the definition of measurability according to RECIST v1.1.

    Note: Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation.

  10. Willingness and ability to provide a tumor biopsy from a metastatic site or the primary breast tumor at the time of the inclusion to perform exploratory studies. If not feasible, patient eligibility should be evaluated by Sponsor's qualified designee.
  11. Willingness to provide blood samples for exploratory studies at baseline, after two weeks of study treatment and at progression (or study treatment termination prior to start alternative anti cancer therapy).
  12. Patients relapsing on a cyclin-dependent kinase (CDK) 4/6 inhibitor based regimen in the neoadjuvant or adjuvant setting will be suitable for the study if disease progression is confirmed after at least 12 months following CDK 4/6 treatment completion.
  13. No prior systemic therapy for unresectable locally advanced or metastatic disease.
  14. Radiation therapy for metastatic disease is permitted but the patient must have fully recovered from the acute effects and at least 14 days must have elapsed between the last dose and randomization.

    Note: For limited-field radiotherapy, at least 7 days must have elapsed between the last dose and randomization.

  15. Resolution of all acute toxic effects of prior anti cancer therapy to Grade ≤1 as determined by the NCI-CTCAE v 5.0 (except for Grade ≤2 neuropathy, alopecia, or other toxicities not considered a safety risk for the patient at investigator's discretion) within at least 14 days prior to study Day 1.
  16. Adequate hematologic and organ function within 14 days before the first study treatment on Day 1 of Cycle 1, defined by the following:

    1. Hematological: White blood cell count >3.0 × 109/L; Absolute neutrophil count ≥1.5 × 109/L (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1); Platelet count ≥100 × 109/L (without transfusion within 2 weeks prior to Cycle 1, Day 1); Hemoglobin >9.0 g/dL (without transfusion within 2 weeks prior to Cycle 1, Day 1).
    2. Hepatic:

    i. Serum albumin ≥ 3 g/dL; ii. Total bilirubin ≤ 1.5 × ULN (≤2 × ULN in the case of Gilbert's disease); iii. Aspartate transaminase and alanine transaminase ≤3.0 × ULN (in the case of liver metastases ≤5 × ULN); iv. Alkaline phosphatase ≤2.5 × ULN (in the case of liver and/or bone metastases ≤ 5 × ULN).

    c. Renal: i. Serum creatinine <1.5 × ULN or creatinine clearance ≥30 mL/min based on Cockcroft-Gault glomerular filtration rate estimation.

    d. Coagulation: i. Partial thromboplastin time (or activated partial thromboplastin time and international normalized ratio ≤1.5×ULN.

  17. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods, or two effective contraceptive methods, as defined in the protocol during the treatment period and for at least 3 weeks after the last dose of study treatment, and agreement to refrain from donating eggs during this same period. Women of childbearing potential must have a negative serum pregnancy test within 7 days before study treatment initiation.
  18. Male patients should also have their partners who are women of childbearing potential use highly effective contraceptive methods, or two effective contraceptive methods, as defined in the protocol during the treatment period and for at least 3 weeks after the last dose of study treatment and refrain from donating sperm during this period.
  19. Able to swallow oral medication.
  20. Patients who are reliable, willing to be available for the duration of the study and are willing to follow study procedures.

Exclusion Criteria:

  1. Known hypersensitivity to abemaciclib, letrozole, fulvestrant, paclitaxel, and/or any of their excipients.
  2. Are currently receiving an investigational drug in a clinical study or participating in any other type of medical research judged not to be scientifically or medically compatible with this study.

    Note: For patients who stopped receiving an investigational drug in another clinical study, a washout period of 21 days or 5-half-lives (whichever is shorter) must be observed before entering the trial.

  3. Formal contraindication to ET defined as visceral crisis and rapidly or symptomatic progressive visceral disease.
  4. Known concurrent malignancy or malignancy within 5 years of study enrollment except for carcinoma in situ of the cervix, non melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the medical monitor is required.
  5. Known active brain metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable for ≥4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for ≥14 days prior to first dose of study treatment.
  6. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  7. Major surgical procedure within 14 days prior to treatment initiation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis.

    Note: Placement of central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure and is therefore permitted.

  8. Active bleeding diathesis, previous history of bleeding diathesis, or chronic anti-coagulation treatment (the use of low molecular weight heparin is allowed if used prophylactically).
  9. Serious and/or uncontrolled pre existing 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 <30 ml/min], history of major surgical resection involving the stomach or small bowel, or pre-existing Crohn's disease or ulcerative colitis or a pre existing chronic condition resulting in baseline Grade 2 or higher diarrhea).
  10. Current known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antibody [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  11. Active bacterial or fungal infection at the time of enrolment (requiring antibiotics or antifungal agents at time of initiating study treatment).
  12. 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.
  13. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through at least 3 weeks after the last dose of study treatment.

Information from the National Library of Medicine

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): NCT04603183


Contacts
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Contact: Carolina Herrero +34 673 973 252 carol.herrero@medsir.org
Contact: Alicia García-Sanz + 34 932 214 135 alicia.garcia@medsir.org

Locations
Show Show 30 study locations
Sponsors and Collaborators
MedSIR
Eli Lilly and Company
Investigators
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Principal Investigator: Antonio Llombart-Cussac Arnau de Vilanova Hospital, Valencia (Spain)
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Responsible Party: MedSIR
ClinicalTrials.gov Identifier: NCT04603183    
Other Study ID Numbers: MedOPP321
2020-001648-24 ( EudraCT Number )
First Posted: October 26, 2020    Key Record Dates
Last Update Posted: July 13, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Aggression
Behavioral Symptoms
Paclitaxel
Albumin-Bound Paclitaxel
Letrozole
Fulvestrant
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists