A Phase II Randomized Trial of Olaparib (NSC-747856) Administered Concurrently With Radiotherapy Versus Radiotherapy Alone for Inflammatory Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Biospecimen Collection
- Conditions
- Breast Inflammatory Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 300
- Locations
- 426
- Primary Endpoint
- Invasive Disease-Free Survival (IDFS)
- Status
- Active, Not Recruiting
- Last Updated
- 19 days ago
Overview
Brief Summary
This phase II trial studies how well radiation therapy with or without olaparib works in treating patients with inflammatory breast cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. It is not yet known whether radiation therapy with or without olaparib may work better in treating patients with inflammatory breast cancer.
Detailed Description
PRIMARY OBJECTIVE: I. To compare the invasive disease-free survival (IDFS) of patients with inflammatory breast cancer receiving concurrent administration of olaparib with standard doses of radiotherapy to the chest wall and regional lymph nodes compared to standard doses of radiotherapy alone to the chest wall and regional lymph nodes. SECONDARY OBJECTIVE: I. To compare the effect of concurrent administration of olaparib with radiotherapy versus radiotherapy alone on improvement in locoregional control (measured by locoregional recurrence-free interval), distant relapse-free survival, and overall survival in inflammatory breast cancer patients. ADDITIONAL OBJECTIVE: I. To collect tissue and whole blood for processing and banking in anticipation of future correlative studies in this patient population. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive olaparib orally (PO) twice daily (BID) the day before standard radiation therapy (RT) commences (Day 0) and throughout the RT course until the last day of RT administration. Olaparib is also continued on weekends (routine days without RT) throughout the RT course. Patients undergo radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. GROUP II: Patients undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. After completion of study treatment, patients are followed up within 5 weeks, then every 3 months until 3 years after registration, and then every 6 months for up to 8 years after registration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have inflammatory breast cancer without distant metastases. All biomarker subtype groups (estrogen receptor \[ER\], progesterone receptor \[PR\], HER2) are eligible. Inflammatory disease will be defined per American Joint Committee on Cancer (AJCC) 8th edition with documentation by history/exam and pathology at the time of diagnosis.
- •All patients must have completed neoadjuvant chemotherapy prior to mastectomy. The chemotherapy regimen is at the discretion of the treating physician but it is recommended that it include at least 4 cycles of anthracycline and/or taxane-based therapy (plus targeted therapy for patients with HER2+ disease). Response to chemotherapy is not a criterion for eligibility (both complete responders and those with residual disease are eligible). Please note that although pathologic complete response (pCR) is not required or excluded, pCR status must be determined post-surgery prior to randomization.
- •All patients must have undergone modified radical mastectomy (with negative margins on ink) with pathologic nodal evaluation (from level I and II axillary lymph node dissection \[ALND\]) at least 3 weeks and no more than 12 weeks prior to randomization, unless they receive additional chemotherapy after mastectomy. Patients must not have gross residual tumor or positive microscopic margins after mastectomy.
- •Additional adjuvant chemotherapy after surgery is allowed at the discretion of the treating physician, either completed prior to randomization or planned for after completion of protocol treatment. If adjuvant chemotherapy is administered after mastectomy, the patient must be randomized at least 3 weeks but no more than 12 weeks after the last dose of adjuvant chemotherapy.
- •Patients must not have a history of radiation therapy to the ipsilateral chest wall and/or regional nodes. Prior radiation therapy to other body sites is allowed.
- •Patients must not be planning to receive any other investigational agents during radiation therapy. Prior therapy, including prior treatment with olaparib or other PARP inhibitor, is allowed.
- •Patients must not have a known hypersensitivity to olaparib or any of the excipients of the product.
- •Patients must not have unresolved or unstable grade 2 or greater toxicity (with the exception of alopecia) from prior administration of another investigational drug and/or prior anti-cancer treatment.
- •Patients must not be planning to receive strong or moderate CYP3A inhibitors or inducers while on olaparib treatment. Patients receiving strong or moderate CYP3A inhibitors must agree to discontinue use at least 2 weeks prior to receiving olaparib. Patients receiving strong or moderate CYP3A inducers must agree to discontinue use at least 5 weeks prior to receiving olaparib.
- •Patients must not be planning to receive live virus or live bacterial vaccines while receiving olaparib and during the 30 day follow up period
Exclusion Criteria
- Not provided
Arms & Interventions
Group I (olaparib, radiation therapy)
Patients receive olaparib PO BID the day before standard RT commences (Day 0) and throughout the RT course until the last day of RT administration. Olaparib is also continued on weekends (routine days without RT) throughout the RT course. Patients undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
Intervention: Biospecimen Collection
Group I (olaparib, radiation therapy)
Patients receive olaparib PO BID the day before standard RT commences (Day 0) and throughout the RT course until the last day of RT administration. Olaparib is also continued on weekends (routine days without RT) throughout the RT course. Patients undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
Intervention: Olaparib
Group II (radiation therapy)
Patients undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
Intervention: Radiation Therapy
Group I (olaparib, radiation therapy)
Patients receive olaparib PO BID the day before standard RT commences (Day 0) and throughout the RT course until the last day of RT administration. Olaparib is also continued on weekends (routine days without RT) throughout the RT course. Patients undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
Intervention: Survey Administration
Group I (olaparib, radiation therapy)
Patients receive olaparib PO BID the day before standard RT commences (Day 0) and throughout the RT course until the last day of RT administration. Olaparib is also continued on weekends (routine days without RT) throughout the RT course. Patients undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
Intervention: Radiation Therapy
Group II (radiation therapy)
Patients undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
Intervention: Biospecimen Collection
Group II (radiation therapy)
Patients undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
Intervention: Survey Administration
Outcomes
Primary Outcomes
Invasive Disease-Free Survival (IDFS)
Time Frame: Up to 8 years
Time from date of registration to date of first invasive recurrence (local, regional or distant), second invasive primary cancer (breast or not), or death due to any cause. Patients last known to be alive who have not experienced recurrence or second primary cancer are censored at their last contact date. Analysis will be on an intent-to-treat basis and will estimate the survival endpoints using the product-limit method of Kaplan-Meier and will compare the time-to-event distributions using log-rank test statistics. Hazard ratios will be calculated from Cox regression analyses. Effect modification by the stratification variables will be tested as interactions with treatment and separate hazard ratios with 95% confidence intervals by major subgroups will be displayed in a forest plot to examine for consistency of the treatment effect over these subgroups.
Secondary Outcomes
- Distant Relapse-Free Survival (Distant Recurrence-Free Survival)(Up to 8 years)
- Locoregional Recurrence-Free Interval (Local Disease-Free Interval [LDFI])(Up to 8 years)
- Overall Survival(Up to 8 years)