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Adj. Dyn. Marker-adjusted Personalized Therapy Comparing Abemaciclib + SOC ET vs. SOC ET in Clinical or Genomic High Risk, HR+/HER2- EBC (ADAPTlate)

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ClinicalTrials.gov Identifier: NCT04565054
Recruitment Status : Recruiting
First Posted : September 25, 2020
Last Update Posted : August 25, 2021
Sponsor:
Collaborators:
Eli Lilly and Company
Genomic Health®, Inc.
Information provided by (Responsible Party):
West German Study Group

Brief Summary:
Patients with breast cancer, who have completed first line therapy (e.g., radiotherapy, chemotherapy, surgery), and who have to be identified with having a high risk of recurrence of cancer, will be eligible for the study. This patient group is currently offered a standard of care chemotherapy plus endocrine therapy (ET). The study investigates whether the patient group with high-risk early breast cancer benefits from treatment with the medication abemaciclib in combination with ET compared to ET alone.

Condition or disease Intervention/treatment Phase
Breast Cancer Female Drug: Abemaciclib 50 MG; 150mg 1-0-1 per os Phase 3

Detailed Description:

The WSG ADAPT trial program is one of the first new generation trials addressing the issue of individualization of (neo)-adjuvant decision-making in early breast cancer (EBC) in a subtype-specific manner. The first WSG ADAPT umbrella trial (NCT01779206) aimed to establish early predictive molecular surrogate markers for response after a short 3-week induction treatment.

The goals of the WSG ADAPT trial program - early response assessment and subtype-specific therapy tailoring to those patients who are most likely to benefit - have contributed to the positive national and international feedback regarding the ADAPT-concept as a whole.

The aim of this ADAPTlate phase-III-trial is to gain further knowledge of the group of patients at high risk for disease recurrence, who have completed definite locoregional therapy (with or without neoadjuvant or adjuvant chemotherapy). This patient group is currently offered an adjuvant chemotherapy plus endocrine therapy. Yet, the high-risk population only receives suboptimum benefit from standard ET and often develops resistance against ET at time of recurrence. With ADAPTlate it is planned to investigate if the high-risk patient group identified during the screening phase derives additional benefit from treatment with abemaciclib in combination with ET compared to ET alone.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: multicenter, interventional, prospective, two-arm, randomized, open-label, controlled adjuvant, phase-III trial evaluating the efficacy and safety of abemaciclib with endocrine therapy (ET) versus standard-of-care endocrine therapy in early breast cancer (EBC) patients with molecular HR+/HER2- subtype.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjuvant Dynamic Marker - Adjusted Personalized Therapy Comparing Abemaciclib Combined With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy in (Clinical or Genomic) High Risk, HR+/HER2- Early Breast Cancer (ADAPTlate)
Actual Study Start Date : September 2, 2020
Estimated Primary Completion Date : August 2026
Estimated Study Completion Date : December 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Abemaciclib

Arm Intervention/treatment
Experimental: Abemaciclib plus ET
Abemaciclib 150 mg, 2 x daily, resulting in 300 mg/day, oral, 24 months plus endocrine treatment of physician´s choice
Drug: Abemaciclib 50 MG; 150mg 1-0-1 per os
Experimental: Abemaciclib plus ET Abemaciclib 150 mg, 2 x daily, resulting in 300 mg/day, oral, 24 months plus endocrine treatment of physician´s choice

No Intervention: Standard-of-care ET

Standard-of-care ET according to clinical guidelines.

Premenopausal patients:

  • Either aromatase inhibitor + GnRH agonist
  • or Tamoxifen +/- GnRH-agonist (as per investigator´s decision) or

Postmenopausal patients:

  • Either Aromatase inhibitor
  • or Tamoxifen OR



Primary Outcome Measures :
  1. invasive disease-free survival (iDFS) [ Time Frame: at end of study, 3-6 years after start of study treatment ]
    superiority in invasive disease-free survival (iDFS) of abemaciclib + endocrine therapy vs. standard-of-care endocrine therapy in patients with HR+/HER2- high risk breast cancer.


Secondary Outcome Measures :
  1. overall survival (OS) [ Time Frame: at end of study, 3-6 years after start of treatment ]
    assessment of overall survival (OS) and distant DFS (dDFS) in both arms

  2. differences in overall survival (OS) and dDFS [ Time Frame: at end of study, 3-6 years after start of study treatment ]
    differences in overall survival (OS) and dDFS between arms

  3. subgroup and multivariable survival analyses [ Time Frame: at end of study, 3-6 years after start of study treatment ]
    subgroup and multivariable survival analyses

  4. CNS metastases [ Time Frame: at end of study, 3-6 years after start of study treatment ]
    occurrence of CNS metastases

  5. EORTC QLQ-C30 [ Time Frame: at end of study, on average 3-6 years after start of treatment ]
    quality of life (QoL)

  6. EORTC QLQ-BR23 [ Time Frame: at end of study, on average 3-6 years after start of treatment ]
    quality of life (QoL)

  7. EQ-5D-5L [ Time Frame: at end of study, on average 3-6 years after start of treatment ]
    quality of life (QoL)



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:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A. Prior to REGISTRATION

  1. Written informed consent prior to any study procedures (outcomes of standard-of-care procedures performed before signing of informed consent by the patient but within allowed screening period can be used for screening of patient).
  2. Female.
  3. ≥ 18 years of age. 4a. EITHER: (Post)menopausal status at the time of initiation of adjuvant study medication

    • patient underwent bilateral oophorectomy, or
    • age ≥ 60, or
    • age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, or ovarian suppression) and/or FSH and estradiol in the postmenopausal range per local normal range.

      4b. OR: Pre-menopausal patients:

    • confirmed negative serum or urine pregnancy test (β-hCG) before starting study treatment, or
    • patient has had a hysterectomy.

5. Histologically confirmed diagnosis of primary estrogen-receptor positive and/or progesterone-receptor positive early breast cancer by local laboratory. In case the receptor status from local pathology is unclear a central pathology review is obligatory. Results must be known prior to randomization.

6. Patient has HER2-negative breast cancer defined as

  • a negative in-situ hybridization test or an IHC status of 0, 1+, or 2+,
  • if IHC is 2+, a negative in-situ hybridization (FISH, CISH, or SISH) test is required (based on the analyzed tissue sample at initial diagnosis by a local laboratory).

    7. Completed local therapy of breast cancer according to current guidelines. 8. Completed or ongoing endocrine therapy for 2-6 years after primary diagnosis without any signs of distant or local relapse as well secondary malignancy.

    9a. Known high clinical risk, defined as either one of the following criteria:

  • c/pN 2-3,
  • pN 0-1 and high CTS5 score,
  • cN 1 or G3 tumor and non-pCR after neoadjuvant chemotherapy
  • pN0-1 and G3 with Ki-67 pre-treatment > 40%; OR 9b. Known high genomic risk, defined as either one of the following criteria:
  • c/pN 1 with RS (Oncotype Dx®) >18,
  • c/pN 0 with RS >25,
  • high risk by PROSIGNA® (score > 60 in N 0 and >40 in N+) or EPclin® (Score >3.3287), or MammaPrint® within clinical routine; OR

In case the tumor is of intermediate clinical risk, but genomic risk is not known at registration:

9c. Intermediate clinical and unknown genomic risk c/pN 0-1 in luminal-B-like tumor (G3 and/or Ki-67 pre-treatment ≥ 20%), AND

  • RS >18 (Oncotype Dx® in screening phase) in patients with c/pN 1, or
  • RS >25 (Oncotype Dx® in screening phase) in patients with c/pN 0.

B. Prior to RANDOMIZATION in the study 10. No clinical evidence of distant metastasis (confirmation recommended prior to randomization by CT thorax / abdomen, chest X-ray, liver ultrasound, bone scan, or PET-CT, respectively).

11. Patient has available tumor tissue from primary diagnostic biopsy. 12. No contraindication for adjuvant ET. 13. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 14. Patient has adequate bone marrow and organ function as defined by the following laboratory values:

  • absolute neutrophil count ≥ 1.5 × 109/L (without administration of any growth stimulation factors within 30 days prior to inclusion),
  • platelets ≥ 100 × 109/L,
  • hemoglobin ≥ 8.0 g/dL (without any RBC transfusion within 30 days prior to inclusion),
  • total bilirubin <1.5 ULN, except for patients with Gilbert's Syndrome who may only be included if the total bilirubin is ≤ 2.0 × ULN or direct bilirubin within normal ranges,
  • aspartate transaminase (AST) < 3 × ULN,
  • alanine transaminase (ALT) < 3 × ULN,
  • serum creatinine ≤ 1.5 x ULN. 15. Ability to swallow abemaciclib tablets or to administer other study medication, respectively.

    16. Ability to communicate with the investigator and comply with study procedures.

    17. Willing to receive therapy by the clinical site, as required by the protocol.

Exclusion Criteria:

Patients eligible for inclusion in this study must not meet any of the following criteria:

  1. Patient with distant metastases of breast cancer beyond regional lymph nodes.
  2. Previously received CDK 4/6 inhibitor.
  3. Patient with a known hypersensitivity to any of the excipients of abemaciclib or standard-of-care endocrine therapy.
  4. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
  5. Patient has not recovered from clinical and laboratory acute toxicities related to prior anticancer therapies to NCI CTCAE version 5.0 Grade ≤ 1 (polyneuropathy ≤ 2 is allowed).
  6. Patient has a concurrent malignancy or non-breast malignancy within 5 years prior to randomization.
  7. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small-bowel resection).
  8. Patient has any active systemic bacterial infection (requiring intravenous antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment.
  9. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator´s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study, or compromise compliance with the protocol (e.g., 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 Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea, etc.).
  10. Patient has a personal 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.
  11. Patient is currently receiving any of the following substances, which cannot be discontinued 7 days prior to day 1 of study treatment:

    o concomitant medications and herbal supplements, that are strong inducers or inhibitors of CYP3A4.

  12. Participation in a prior investigational study within 30 days prior to enrollment.
  13. Not able to understand and to comply with study instructions and requirements.
  14. Pregnant or nursing (lactating) woman.
  15. Woman of child-bearing potential defined as woman physiologically capable of becoming pregnant, unless she is using highly effective methods of contraception during the study treatment and for 21 days after stopping the treatment:

    1. total abstinence (when this is in line with the preferred and usual lifestyle of the patient).
    2. female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment.
    3. male partner sterilization (at least 6 months prior to study screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient.
    4. placement of an intrauterine device (IUD).
    5. use of condom + spermicide.
  16. Use of oral (estrogen and progesterone), transdermal, injected, or implanted hormonal methods of contraception as well as hormonal replacement therapy.

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): NCT04565054


Contacts
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Contact: Anja Braschoß, MD +4917682119153 anja.braschoss@wsg-online.com
Contact: Bettina Bonn, Dr. +4921615662328 bettina.bonn@wsg-online.com

Locations
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Germany
Praxis für interdisziplinäre Onkologie & Hämatologie Recruiting
Freiburg, Baden-Württemberg, Germany, 79110
Contact: Matthias Zaiss, Dr         
Contact: Norbert Marschner, Dr         
Brustzentrum, LMU Klinikum, Ludwig-Maximilians-Universität, Recruiting
Muenchen, Bayern, Germany
Contact: Nadia Harbeck, Prof. Dr. med.       nadia.harbeck@med.uni-muenchen.de   
Sub-Investigator: Tom Degenhardt, Dr. med.         
Principal Investigator: Nadia Harbeck, PRof. Dr. med.         
Niels-Stensen-Kliniken Franziskus-Hospital Recruiting
Georgsmarienhütte, Niedersachsen, Germany, 49124
Contact: Kerstin Lüdtke-Heckenkamp, Dr. med.    +49 541 5022466    jost.wamhoff@niels-stensen-kliniken.de   
Contact: Jost Wamhoff, Dr. med.    +49 541 5022466    jost.wamhoff@niels-stensen-kliniken.de   
Principal Investigator: Kerstin Lüdtke-Heckenkamp, Dr. med.         
Sub-Investigator: Jost Wamhoff, Dr. med.         
Diakovere Henriettenstift Frauenklinik Recruiting
Hannover, Niedersachsen, Germany, 30559
Contact: Angela Kentsch, Dr. med.    +49 511 2893455    angela.kentsch@diakovere.de   
Contact: Sabine Anolke    +49 511 2893455    sabine.anolke@diakovere.de   
Principal Investigator: Kristina Lübbe, Dr. med.         
Sub-Investigator: Angela Kentsch, Dr. med.         
Krankenhaus Köln Holweide, Brustzentrum Recruiting
Köln, Nordrhein-Westfalen, Germany, 51067
Contact: Mathias Warm, MD    +49 221 8907 ext 6707    warmm@kliniken-koeln.de   
Principal Investigator: Mathias Warm, Prof. Dr. med.         
Sub-Investigator: Myriam Vincent, Dr. med.         
Universitätsklinikum Aachen, Frauenklinik - Senologie Recruiting
Aachen, NRW, Germany, 52074
Contact: Katja Krauss, Dr    +49-241-8080700    kkrauss@ukaachen.de   
Principal Investigator: Katja Krauss, Dr. med.         
Sub-Investigator: Elmar Stickeler, Prof. Dr. med.         
Kliniken Essen-Mitte, Klinik für Senologie/Interdisziplinäres Brustzentrum Recruiting
Essen, NRW, Germany, 45136
Contact: Sherko Kuemmel, Prof. Dr    +49-201-17433005    s.kuemmel@kliniken-essen-mitte.de   
Contact: Dorothea Schindowski    +49-201-17433005    d.schindowski@kliniken-essen-mitte.de   
Principal Investigator: Sherko Kuemmel, Prof. Dr.         
Sub-Investigator: Mattea Reinisch, Dr. med.         
Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus Recruiting
Moenchengladbach, NRW, Germany, 41061
Contact: Oleg Gluz, PD. Dr. med.       oleg.gluz@wsg-online.com   
Contact: Iris Scheffen, Dr. med.       iris.scheffen@wsg-online.com   
Principal Investigator: Oleg Gluz, PD Dr. med.         
Mammazentrum HH am Krankenhaus Jerusalem Recruiting
Hamburg, Germany, 20357
Contact: Felix Hilpert, Prof. Dr. med.    +49 40 44190671    hilpert@mammazentrum.eu   
Contact: Silke Kassner    +49 40 44190557    kassner@mammazentrum.eu   
Sub-Investigator: Felix Hilpert, Prof. Dr. med.         
Principal Investigator: Christian Schem, Prof. Dr. med.         
Sponsors and Collaborators
West German Study Group
Eli Lilly and Company
Genomic Health®, Inc.
Investigators
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Principal Investigator: Oleg Gluz, PD Dr. med. Westdeutsche Studiengruppe GmbH
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Responsible Party: West German Study Group
ClinicalTrials.gov Identifier: NCT04565054    
Other Study ID Numbers: WSG-AM11
2019-001488-60 ( EudraCT Number )
First Posted: September 25, 2020    Key Record Dates
Last Update Posted: August 25, 2021
Last Verified: August 2021
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
Keywords provided by West German Study Group:
early breast cancer
ADAPT
endocrine therapy
abemaciclib
high risk
HER2 negative
HR positive
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases