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.
Signed and dated written informed consent.
Subjects 18 years of age.
Subjects 18 years of age.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
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)
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.
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)
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
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.
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
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
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
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).
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
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.
Pregnant or breastfeeding females.
Signed and dated written informed consent.
Signed and dated written informed consent.
Subjects 18 years of age.
Subjects 18 years of age.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
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)
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.
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)
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
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.
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
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
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
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).
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
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.
Pregnant or breastfeeding females.
