Abemaciclib in Treating Patients With Surgically Resectable, Chemotherapy Resistant, Triple Negative Breast Cancer

Launched by MAYO CLINIC · Jun 5, 2019

Keywords

ClinConnect Summary

This clinical trial is studying a medication called abemaciclib to see how well it works for women with a specific type of breast cancer known as triple-negative breast cancer. This trial focuses on patients whose cancer can be surgically removed but has not responded to previous treatments with chemotherapy alone or in combination with another drug called pembrolizumab. Abemaciclib works by blocking certain enzymes that cancer cells need to grow, which may help stop the cancer from getting worse.

To participate in this trial, women must be at least 18 years old and have a confirmed diagnosis of triple-negative breast cancer that has not spread to other parts of the body. They should have already undergone neoadjuvant chemotherapy (treatment given before surgery) and still have some cancer present. Participants should be able to take oral medication and be willing to provide samples for research. Throughout the trial, participants will receive abemaciclib and will be monitored closely for any side effects or changes in their condition. If you or a loved one meet the eligibility criteria and are interested in participating, this trial could offer an opportunity to contribute to important breast cancer research.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • Women of age \>=18 years
• • PRE-REGISTRATION: Clinical T1-4, N0-3, M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy) by American Joint Committee on Cancer (AJCC) staging version 8.
• • Note: Benign breast disease, lobular carcinoma in situ (LCIS) or ductal carcinoma in situ (DCIS) in the ipsilateral or contralateral breast is allowed.
• • Note: Additional ipsilateral or contralateral invasive breast cancer is allowed. The index lesion is the largest triple-negative, chemotherapy-resistant lesion.
• • PRE-REGISTRATION: Histological confirmation of triple negative invasive breast cancer (defined as estrogen receptor \[ER\] =\< 10%, progesterone receptor \[PR\] =\< 10% and HER2 not amplified by in situ hybridization \[ISH\] or immunohistochemistry \[IHC\] 0/1) at diagnosis.
• * PRE-REGISTRATION: Cohort A: CLOSED TO PRE-REGISTRATION and REGISTRATION as of protocol amendment 6 (04/14/2023) Neoadjuvant chemotherapy (NAC) with one of the following regimens that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:
• • Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC)
• • Note: Carboplatin may be added to these regimens
• • AC or EC or FEC followed by docetaxel or paclitaxel
• • Note: Carboplatin may be added to these regimens
• • Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)
• • Docetaxel in combination with cyclophosphamide (TC) (for patients who are not candidates for anthracyclines)
• • Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel) (for patients who are not candidates for anthracyclines)
• * PRE-REGISTRATION: Cohort B: Neoadjuvant chemotherapy (NAC) with one of the following regimens in combination with pembrolizumab that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:
• • Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) Note: Carboplatin may be added to these regimens
• • AC or EC or FEC followed by docetaxel or paclitaxel \[Note: Carboplatin may be added to these regimens\]
• • Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)
• • Docetaxel in combination with cyclophosphamide (TC)
• • Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel)
• • PRE-REGISTRATION: Residual lesion/enhancement seen in the breast on breast imaging performed after completion of NAC.
• • PRE-REGISTRATION: Able to swallow oral medication.
• • PRE-REGISTRATION: Willing to undergo biopsy for research.
• • PRE-REGISTRATION: Willing to provide tissue and blood samples for correlative research purposes.
• • PRE-REGISTRATION: Willing to stop use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =\< 7 days prior to registration.
• • PRE-REGISTRATION: Provide written informed consent.
• • REGISTRATION: Registration must occur =\< 56 days after last dose of NAC.
• • REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2.
• * REGISTRATION: COHORT B GROUP 4 ONLY: The following laboratory values obtained after completion of NAC but =\< 14 days prior to registration:
• • REGISTRATION: COHORT B GROUP 4 ONLY: Absolute neutrophil count (ANC) \>= 1500/mm\^3.
• • REGISTRATION: COHORT B GROUP 4 ONLY: Platelets (PLT) \>= 100,000/mm\^3.
• • REGISTRATION: COHORT B GROUP 4 ONLY: Hemoglobin (HgB) \>= 8.0 g/dL.
• • REGISTRATION: COHORT B GROUP 4 ONLY: Total bilirubin =\< 1.5 x upper limit of normal (ULN).
• • REGISTRATION: COHORT B GROUP 4 ONLY: Aspartate transaminase (AST) serum glutamic oxaloacetic transaminase (SGOT) =\< 3 x ULN.
• • REGISTRATION: COHORT B GROUP 4 ONLY: Alanine transaminase (ALT) serum glutamate pyruvate transaminase (SGPT) =\< 3 x ULN.
• • REGISTRATION: COHORT B GROUP 4 ONLY: Serum creatinine =\< 1.5 x ULN.
• • REGISTRATION: GROUP 2 ONLY: Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only.
• Exclusion Criteria:
• • PRE-REGISTRATION: History of deep venous thrombosis (DVT) or pulmonary embolisms (PE) =\< 12 months prior to preregistration; OR Active DVT and/or PE requiring anti-coagulant therapy.
• • NOTE: Patients who are on anti-coagulant therapy for maintenance are eligible as long as the DVT and/or PE was \> 12 months prior to enrollment and there is no evidence for active thrombosis (either DVT or PE).
• • NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.
• • PRE-REGISTRATION: Prior treatment with CDK 4/6 inhibitors (e.g. palbociclib, ribociclib, abemaciclib, etc.)
• • PRE-REGISTRATION: Prior treatment with radiation for this breast cancer.
• • PRE-REGISTRATION: Prior incisional or excisional breast biopsy for this cancer.
• • PRE-REGISTRATION: Any contraindications to pre-registration biopsy (such as bleeding diatheses, etc.).
• • PRE-REGISTRATION: Receiving any investigational agent which would be considered as a treatment for the primary neoplasm.
• • PRE-REGISTRATION: Other active malignancy =\< 3 years prior to registration.
• • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
• • NOTE: If there is a history of prior malignancy, they must not be receiving another specific treatment for prior malignancy.
• • PRE-REGISTRATION: Biopsy proven Stage IV breast cancer.
• • PRE-REGISTRATION: Serious pre-existing medical conditions that 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 preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea).
• * PRE-REGISTRATION: 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).
• • Sudden cardiac arrest.
• • NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.
• * REGISTRATION: COHORT B GROUP 4: Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• • Pregnant persons.
• • Nursing persons.
• • Persons of childbearing potential who are unwilling to employ adequate contraception.
• • REGISTRATION: COHORT B GROUP 4: Failure to recover to grade 1 or lower from effects of neoadjuvant chemotherapy.
• • Exceptions: Residual alopecia and grade 2 peripheral neuropathy are allowed.
• • REGISTRATION: COHORT B GROUP 4: Concurrent use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =\< 7 days prior to registration.
• * REGISTRATION: COHORT B GROUP 4: Known infections as follows (NOTE: Screening is not required for enrollment):
• • Active systemic bacterial infection requiring intravenous antibiotics.
• • Active fungal infection (requiring intravenous or oral antifungal treatment).
• • Detectable viral infections (e.g. known human immunodeficiency virus \[HIV\], known active hepatitis B or C).
• • REGISTRATION: COHORT B GROUP 4: Concurrent use of chemotherapy, radiotherapy, immunotherapy, or other components of neoadjuvant treatment.
• • NOTE: Patients must complete all elements of NAC ≥21 days prior to starting abemaciclib.