RECRUITING

Olaparib With Cediranib or AZD6738 for the Treatment of Advanced or Metastatic Germline BRCA Mutated Breast Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase II trial studies how well olaparib with cediranib or AZD6738 works in treating patients with germline BRCA mutated breast cancer that has spread to other places in the body (advanced or metastatic). Olaparib, cediranib, and AZD6738 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Official Title

Overcoming PARP Inhibitor Resistance in BRCA Germline Mutation Positive Advanced Breast Cancer

Quick Facts

Study Start:2020-07-28

Study Completion:2025-03-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04090567

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Provision of informed consent prior to any study specific procedures 2. Women age greater than 18 years with advanced/metastatic HER2 negative, BRCA germline positive breast cancer. Estrogen receptor positive (ER+) patients must have progressed on a prior endocrine therapy or are considered inappropriate for any FDA approved endocrine therapies for ER+ breast cancer. 3. Eligible patients must agree to a mandatory fresh biopsy (excluding bone) at screening. In addition, if available, an archival tissue sample will also be collected at screening. 4. Patients must have normal organ and bone marrow function measured within 28 days (baseline screening) as defined below: * Hemoglobin (Hgb) \>/= 10.0 g/dL with no blood transfusion in the past 28 days prior to the administration * Absolute neutrophil count (ANC) \>/= 1.5 x 109/L with no GCSF administration within 28 days prior to administration of study treatment * Platelet count \>/= 100 x 109/L * Total bilirubin \</= 1.5 x institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) \</=3.0 x institutional upper limit of normal unless liver metastases are present in which case they must be \</=5x ULN	1. Patients who have had chemotherapy or RT within 3 weeks ( or less than 1 week if on weekly chemotherapy) prior to start of the study agents. or persisting \>/= Grade 2 CTCAE toxicity (except alopecia and Grade 2 peripheral neuropathy) from previous anti-cancer treatment(s), or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. No washout time period is needed for PARP inhibitors. 2. Patients received any other investigational agents within the past 4 weeks. 3. Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should be excluded from this clinical trial. Patient with known and treated brain metastases is allowed in this study if they fulfil the following criteria: The lesions have improved or remained stable radiographically and clinically for at least 6 weeks after completion of brain irradiation or stereotactic brain radiosurgery. Patients can be on steroids not more than 10 mg/day if started 4 weeks prior to initiation of study drug). 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Olaparib or ceralasertib. 5. Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 (See Appendix A) are ineligible, unless discontinues within the washout period (2 weeks for CYP3A4 inhibitors and 4weeks for CYP3A4 inducers) as described in Appendix A. Dihydropyridine calcium-channel blockers are permitted for management of hypertension. Other medications described in Appendix A should be discontinued within the washout period prior to the initiation of study drugs. In addition, patients enrolled in Olaparib+ ceralasertib arm, co-administration of study drug with substrates of OATP1B1 and Pgp (P-glycoprotein) inhibitor or inducer is prohibited. 6. Current use of natural herbal products (see Appendix A) or other complementary alternative medications (CAM) or "folk remedies" should be discontinued 7 days prior to the initiation of study drugs. * 4cm in diameter, all the following criteria must be met: * An ultrasound (US) within the last 6 months will be required to document that it is \</= 5cm * Patient must be asymptomatic from the aneurysm. * Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \>450 milli-second, or patients with congenital long QT syndrome or family history of unexplained sudden death under 40 years of age * Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block).

Inclusion Criteria

Exclusion Criteria

1. Provision of informed consent prior to any study specific procedures
2. Women age greater than 18 years with advanced/metastatic HER2 negative, BRCA germline positive breast cancer. Estrogen receptor positive (ER+) patients must have progressed on a prior endocrine therapy or are considered inappropriate for any FDA approved endocrine therapies for ER+ breast cancer.
3. Eligible patients must agree to a mandatory fresh biopsy (excluding bone) at screening. In addition, if available, an archival tissue sample will also be collected at screening.
4. Patients must have normal organ and bone marrow function measured within 28 days (baseline screening) as defined below:
* Hemoglobin (Hgb) \>/= 10.0 g/dL with no blood transfusion in the past 28 days prior to the administration
* Absolute neutrophil count (ANC) \>/= 1.5 x 109/L with no GCSF administration within 28 days prior to administration of study treatment
* Platelet count \>/= 100 x 109/L
* Total bilirubin \</= 1.5 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) \</=3.0 x institutional upper limit of normal unless liver metastases are present in which case they must be \</=5x ULN

1. Patients who have had chemotherapy or RT within 3 weeks ( or less than 1 week if on weekly chemotherapy) prior to start of the study agents. or persisting \>/= Grade 2 CTCAE toxicity (except alopecia and Grade 2 peripheral neuropathy) from previous anti-cancer treatment(s), or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. No washout time period is needed for PARP inhibitors.
2. Patients received any other investigational agents within the past 4 weeks.
3. Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should be excluded from this clinical trial. Patient with known and treated brain metastases is allowed in this study if they fulfil the following criteria: The lesions have improved or remained stable radiographically and clinically for at least 6 weeks after completion of brain irradiation or stereotactic brain radiosurgery. Patients can be on steroids not more than 10 mg/day if started 4 weeks prior to initiation of study drug).
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Olaparib or ceralasertib.
5. Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 (See Appendix A) are ineligible, unless discontinues within the washout period (2 weeks for CYP3A4 inhibitors and 4weeks for CYP3A4 inducers) as described in Appendix A. Dihydropyridine calcium-channel blockers are permitted for management of hypertension. Other medications described in Appendix A should be discontinued within the washout period prior to the initiation of study drugs. In addition, patients enrolled in Olaparib+ ceralasertib arm, co-administration of study drug with substrates of OATP1B1 and Pgp (P-glycoprotein) inhibitor or inducer is prohibited.
6. Current use of natural herbal products (see Appendix A) or other complementary alternative medications (CAM) or "folk remedies" should be discontinued 7 days prior to the initiation of study drugs.
* 4cm in diameter, all the following criteria must be met:
* An ultrasound (US) within the last 6 months will be required to document that it is \</= 5cm
* Patient must be asymptomatic from the aneurysm.
* Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \>450 milli-second, or patients with congenital long QT syndrome or family history of unexplained sudden death under 40 years of age
* Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block).

Contacts and Locations

Study Contact

Banu Arun

CONTACT

713-792-2817

barun@mdanderson.org

Principal Investigator

Banu Arun

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

M D Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Banu Arun, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-07-28

Study Completion Date2025-03-31

Study Record Updates

Study Start Date2020-07-28

Study Completion Date2025-03-31

Terms related to this study

Additional Relevant MeSH Terms

Advanced Breast Carcinoma
Anatomic Stage III Breast Cancer AJCC v8
Anatomic Stage IIIA Breast Cancer AJCC v8
Anatomic Stage IIIB Breast Cancer AJCC v8
Anatomic Stage IIIC Breast Cancer AJCC v8
Anatomic Stage IV Breast Cancer AJCC v8
Germline BRCA1 Gene Mutation
Germline BRCA2 Gene Mutation
HER2/Neu Negative
Metastatic Breast Carcinoma
Prognostic Stage III Breast Cancer AJCC v8
Prognostic Stage IIIA Breast Cancer AJCC v8
Prognostic Stage IIIB Breast Cancer AJCC v8
Prognostic Stage IIIC Breast Cancer AJCC v8
Prognostic Stage IV Breast Cancer AJCC v8