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

ConditionsAdvanced Breast CarcinomaAnatomic Stage III Breast Cancer AJCC v8Anatomic Stage IIIA Breast Cancer AJCC v8Anatomic Stage IIIB Breast Cancer AJCC v8Anatomic Stage IIIC Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Germline BRCA1 Gene MutationGermline BRCA2 Gene MutationHER2/Neu NegativeMetastatic Breast CarcinomaPrognostic Stage III Breast Cancer AJCC v8Prognostic Stage IIIA Breast Cancer AJCC v8Prognostic Stage IIIB Breast Cancer AJCC v8Prognostic Stage IIIC Breast Cancer AJCC v8Prognostic Stage IV Breast Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorM.D. Anderson Cancer Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Hemoglobin (Hgb) >/= 10.0 g/dL with no blood transfusion in the past 28 days prior to the administration

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Cediranib

    Drug

    Given PO

  • Ceralasertib

    Drug

    Given PO

  • Olaparib

    Drug

    Given PO

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: Arm I (olaparib plus cediranib)Experimental treatment 2 interventions
Group B: Arm II (olaparib plus ceralasertib)Experimental treatment 2 interventions

Trial outcomes

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.

Time frame
Up to 30 days post treatment

Secondary outcomes

1

Progression free survival (PFS)

PFS will be estimated using the Kaplan-Meier method with the 95% confidence intervals (CIs). Will analyze aggregate data from selected arms of the trial using Cox proportional hazards and logistic regression to identify study factors related to outcomes including response and PFS. Hazard ratios and odds ratios with their 95% confidence intervals and p-values will be reported. Model assumptions will be verified.

Time frame
Up to 30 days post treatment
2

Duration of response (DOR)

DOR will be estimated using the Kaplan-Meier method with the 95% CIs. Will analyze aggregate data from selected arms of the trial using Cox proportional hazards and logistic regression to identify study factors related to outcomes including response and PFS. Hazard ratios and odds ratios with their 95% confidence intervals and p-values will be reported. Model assumptions will be verified.

Time frame
Up to 30 days post treatment

Other outcomes

1

Biomarker analysis

Will be done using Fisher's exact tests, Mann-Whitney U tests or McNemar's test will be applied depending the type of data we observe. For the pre- and post- therapy biomarker and outcome analysis, paired t- test or Wilcoxon signed-rank will be applied for the continuous variables. McNemar's test will be applied for categorical variables. Fisher's exact test will be applied for the association between hypoxia positivity and objective response. Will use this information to estimate the 95% confidence intervals for future pivotal trials.

Time frame
Up to 30 days post treatment

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

M.D. Anderson Cancer Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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