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

NCT04090567 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2018-0062NCI-2019-04148
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Breast Carcinoma; 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; 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

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Defined as proportion of patients with reduction in tumor burden (complete response \[CR\] or partial response \[PR\] as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The exact two-sided 95% confidence interval for the ORR will be reported.

  Up to 30 days post treatment

Secondary Outcomes (2)

• Progression free survival (PFS)

  Up to 30 days post treatment

• Duration of response (DOR)

  Up to 30 days post treatment

Other Outcomes (1)

• Biomarker analysis

  Up to 30 days post treatment

Study Arms (2)

Arm I (olaparib plus cediranib)

EXPERIMENTAL

Patients receive olaparib PO BID and cediranib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cediranib; Drug: Olaparib

Arm II (olaparib plus ceralasertib)

EXPERIMENTAL

Patients receive olaparib PO BID on days 1-28 and ceralasertib PO QD on days 1-7. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Ceralasertib; Drug: Olaparib

Interventions

Cediranib DRUG

Given PO

Also known as: AZD2171

Arm I (olaparib plus cediranib)

Ceralasertib DRUG

Given PO

Also known as: AZD6738

Arm II (olaparib plus ceralasertib)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Arm I (olaparib plus cediranib); Arm II (olaparib plus ceralasertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• 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.
• 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.
• 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
• \) Eastern Cooperative Oncology Group (ECOG) performance status 0-1 5) Patients must have life expectancy \>/= 16 weeks. 6) Negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on Cycle 1 day 1 and during the study for child bearing potential women.
• Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥ 60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry and be using highly effective contraception (that is, methods with a failure rate of less than 1% per year) for both male and female subjects if the risk of conception exists (Note: The effects of the trial treatment on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use highly effective contraception, defined in Appendix E or as stipulated in national or local guidelines). Highly effective contraception must be used 30 days prior to first trial treatment administration, for the duration of trial treatment, and at least for 1 month after stopping trial treatment.
• \) Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations. 8) Patient has measurable disease, per RECIST v 1.1. At least one lesion, not previously irradiated or biopsied for this study that can be accurately measured at baseline as \>/= 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI).
• \) Willingness to undergo baseline biopsy of metastatic lesion (repeat biopsy at progression/or end of the study is optional) 10) Willingness to have research blood draw at baseline and at progression/end of the study 11) Patient should have previously treated with any PARP inhibitor ((neo)adjuvant or metastatic) setting) and must have remained on treatment for \>/= 2 months prior to progression of disease.
• \) Able to swallow and retain oral medications and without gastrointestinal (GI) illnesses that would preclude absorption of Olaparib or ceralasertib.
• \) Non-english speaking subject can be enrolled

You may not qualify if:

• 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.
• Patients received any other investigational agents within the past 4 weeks.
• 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).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Olaparib or ceralasertib.
• 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.
• 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.
• \) Patients with concomitant or prior invasive malignancies within the past 5 years. Subjects with treated limited stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible.
• \) Uncontrolled inter-current illness including, but not limited to, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• \) History of myocardial infarction, stroke or transient ischemic attack within 6-12 months. Current condition requiring concurrent use of drugs or biologics with anti-arrhythmic or proarrhythmic potential 11) History of hypertensive crisis or hypertensive encephalopathy within 3 years.
• \) Clinically significant peripheral vascular disease or vascular disease (abdominal aortic aneurysm (\>5cm) or aortic dissection). If known history of abdominal aortic aneurysmwith
• cm 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.
• \) A major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting study drug (percutaneous/endobronchial biopsies are allowed). The patient must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment.
• \) Patients may not have current signs and/or symptoms of bowel obstruction within 3 months prior to starting study drugs, except if it was a temporary incident (improved within \< 24hrs with medical management).

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

cediranib; ceralasertib; olaparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Banu Arun

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Banu Arun

CONTACT

713-792-2817; barun@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: September 16, 2019
• Study Start: July 28, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)