Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
This is an open-label, multicenter, two-arm Phase II clinical trial that will evaluate the impact of 2nd line chemotherapy (i.e. capecitabine) on survival in patients with non-Luminal A hormone receptor-positive (HR+) metastatic breast cancer (MBC)
Breast
Phase II
Adults
Chemotherapy - cytotoxic,
Hormonal Therapy
Capecitabine
Reid, Sonya
Local
UT Southwestern Medical Center, University of Alabama - Birmingham, Vanderbilt University
03-31-2023
Eligibility
18 Years and older
ALL
false
Inclusion Criteria:
Signed and dated written informed consent.
Subjects 18 years of age.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Clinical stage IV invasive mammary carcinoma or unresectable locoregional recurrence of invasive mammary carcinoma that is: * ER (>/=1%) and/or PR (>/= 1%) by IHC and HER2 negative (by IHC or FISH)
Previously exposed to an aromatase inhibitor (AI) or a selective estrogenreceptor modulator/ downregulator (SERM; SERD) + a CDK4/6 inhibitor.
Prior radiation permitted (if completed at least 2 weeks prior to study entry. Patients who have received prior radiotherapy must have recovered from toxicity ( grade 1) induced by this treatment (except for alopecia)
Patients with brain metastasis secondary to breast cancer and clinically stable for more than 4 weeks from completion of radiation treatment and off steroids
Evaluable disease (measurable or non-measurable) * Measurable disease, ie, at least 1 measurable lesion as per RECIST 1.1 (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation) * Patients with bone only disease allowed if possible to evaluate on radiological exams (eg.bone scan, PET/CT, CT, MRI) even if lesions are non-measurable according to RECIST1.1.
Adequate organ function including: * Absolute neutrophil count (ANC) 1.5 10\^9/L * Platelets 100 10\^9/L * Hemoglobin 8/g/dL (may have been transfused) * Total serum bilirubin 1.5 times upper limit of normal (ULN) * Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) 2.5 ULN (or 5 ULN if liver metastases are present) * Serum creatinine 1.5 x ULN or estimated creatinine clearance 50mL/min as calculated using the Cockcroft-Gault (CG) equation
For randomized patients only: tumors must be diagnosed as non-Luminal A using the Blueprint and Mammaprint tests
Exclusion Criteria:
Prior chemotherapy in the metastatic setting
Previous malignant disease other than breast cancer within the last 2 years with associated competing risk, with the exception of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or low-risk cancers considered curatively treated (i.e. complete remission achieved at least 2 years prior to first dose of study drugs AND additional therapy not required while receiving study treatment).
Persisting symptoms related to prior therapy that has not reduced to Grade 1 \[National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.0\]; however, menopausal symptoms, alopecia, and sensory neuropathy Grade 2 is acceptable
Pregnant or breastfeeding females.
Signed and dated written informed consent.
Subjects 18 years of age.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Clinical stage IV invasive mammary carcinoma or unresectable locoregional recurrence of invasive mammary carcinoma that is: * ER (>/=1%) and/or PR (>/= 1%) by IHC and HER2 negative (by IHC or FISH)
Previously exposed to an aromatase inhibitor (AI) or a selective estrogenreceptor modulator/ downregulator (SERM; SERD) + a CDK4/6 inhibitor.
Prior radiation permitted (if completed at least 2 weeks prior to study entry. Patients who have received prior radiotherapy must have recovered from toxicity ( grade 1) induced by this treatment (except for alopecia)
Patients with brain metastasis secondary to breast cancer and clinically stable for more than 4 weeks from completion of radiation treatment and off steroids
Evaluable disease (measurable or non-measurable) * Measurable disease, ie, at least 1 measurable lesion as per RECIST 1.1 (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation) * Patients with bone only disease allowed if possible to evaluate on radiological exams (eg.bone scan, PET/CT, CT, MRI) even if lesions are non-measurable according to RECIST1.1.
Adequate organ function including: * Absolute neutrophil count (ANC) 1.5 10\^9/L * Platelets 100 10\^9/L * Hemoglobin 8/g/dL (may have been transfused) * Total serum bilirubin 1.5 times upper limit of normal (ULN) * Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) 2.5 ULN (or 5 ULN if liver metastases are present) * Serum creatinine 1.5 x ULN or estimated creatinine clearance 50mL/min as calculated using the Cockcroft-Gault (CG) equation
For randomized patients only: tumors must be diagnosed as non-Luminal A using the Blueprint and Mammaprint tests
Exclusion Criteria:
Prior chemotherapy in the metastatic setting
Previous malignant disease other than breast cancer within the last 2 years with associated competing risk, with the exception of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or low-risk cancers considered curatively treated (i.e. complete remission achieved at least 2 years prior to first dose of study drugs AND additional therapy not required while receiving study treatment).
Persisting symptoms related to prior therapy that has not reduced to Grade 1 \[National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.0\]; however, menopausal symptoms, alopecia, and sensory neuropathy Grade 2 is acceptable
Pregnant or breastfeeding females.
