Clinical Trials /

Radiation Therapy With or Without Olaparib in Treating Patients With Inflammatory Breast Cancer

NCT03598257

Description:

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 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy with or without olaparib may work better in treating patients with inflammatory breast cancer.

Related Conditions:
  • Inflammatory Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Radiation Therapy With or Without Olaparib in Treating Patients With Inflammatory Breast Cancer
  • Official Title: A Phase II Randomized Trial of Olaparib (NSC-747856) Administered Concurrently With Radiotherapy Versus Radiotherapy Alone for Inflammatory Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: NCI-2018-01519
  • SECONDARY ID: NCI-2018-01519
  • SECONDARY ID: S1706
  • SECONDARY ID: S1706
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT03598257

Conditions

  • Inflammatory Breast Carcinoma

Interventions

DrugSynonymsArms
OlaparibAZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP inhibitor AZD2281Group I (olaparib, radiation therapy)

Purpose

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 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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 OBJECTIVES:

      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 OBJECTIVES:

      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 OBJECTIVES:

      I. To collect tissue and whole blood for processing and banking in anticipation of future
      correlative studies in this patient population.

      OUTLINE: Participants are randomized to 1 of 2 groups.

      GROUP I: Participants 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. Participants undergo radiation therapy 5 days per week for 6 weeks
      in the absence of disease progression or unaccepted toxicity.

      GROUP II: Participants undergo standard radiation therapy 5 days per week for 6 weeks in the
      absence of disease progression or unaccepted toxicity.

      After completion of study treatment, participants 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.
    

Trial Arms

NameTypeDescriptionInterventions
Group I (olaparib, radiation therapy)ExperimentalParticipants 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. Participants undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unaccepted toxicity.
  • Olaparib
Group II (radiation therapy)Active ComparatorParticipants undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unaccepted toxicity

    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) 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 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
    
              -  Patients must not be planning to receive any additional anti-cancer therapy
                 (chemotherapy, endocrine therapy, immunotherapy, biological therapy or other novel
                 agent) while receiving radiotherapy with or without study medication. If a patient is
                 receiving concurrent anti-HER2 targeted therapies, they must not take these
                 medications during the period of radiotherapy (with or without study drug) while
                 enrolled on the study.
    
              -  Patients must have Zubrod performance status 0-2.
    
              -  Absolute neutrophil count (ANC) >= 1000/mm^3 (within 28 days prior to registration)
    
              -  Platelet count >= 100,000/mm^3 (within 28 days prior to registration)
    
              -  Hemoglobin >= 9.0 g/dL (after transfusion if required and within 28 days prior to
                 registration)
    
              -  Patients must have adequate renal function as evidenced by calculated creatinine
                 clearance >= 51 mL/min by Cockcroft-Gault equation, within 28 days prior to
                 registration.
    
              -  Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 28 days prior to
                 registration)
    
                   -  Patients with documented Gilbert's disease may have bilirubin up to 2.5 mg/dL
    
              -  Serum glutamic-oxaloacetic transaminase (SGOT) =< 2.5 x ULN (within 28 days prior to
                 registration)
    
              -  Serum glutamate pyruvate transaminase (SGPT) =< 2.5 x ULN (within 28 days prior to
                 registration)
    
              -  Alkaline phosphatase =< 2.5 x ULN (within 28 days prior to registration)
    
              -  Patients must not have a history of other prior malignancy except for the following:
                 adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer,
                 adequately treated stage I or II cancer from which the patient is currently in
                 complete remission, or any other cancer from which the patient has been disease free
                 for five years
    
              -  Female patients must be postmenopausal or have a negative urine or serum pregnancy
                 test within 14 days prior to registration. Female patients of childbearing potential
                 and male patients with partners of childbearing potential, who are sexually active,
                 must agree to the use of two highly effective forms of contraception during protocol
                 treatment (groups 1 and 2) and for 6 months following the last dose of olaparib (group
                 1).
    
              -  Patients who are breastfeeding must agree to discontinue breastfeeding before
                 receiving olaparib due to potential risk for adverse events in nursing infants
                 secondary to treatment of the mother with olaparib.
    
              -  Patients must not have active uncontrolled infection, symptomatic congestive heart
                 failure, unstable angina pectoris or cardiac arrhythmia.
    
              -  Patients must be able to swallow and retain oral medications and have no known
                 gastrointestinal disorders likely to interfere with absorption of the study
                 medication.
    
              -  Patients must not have a history of a resting electrocardiography (ECG) indicating
                 uncontrolled, potentially reversible cardiac conditions (such as unstable ischemia,
                 uncontrolled symptomatic arrhythmia, congestive heart failure, Fridericia's formula
                 corrected QT interval [QTcF] prolongation > 500 ms, electrolyte disturbances) or
                 congenital long QCYP3T syndrome.
    
              -  Patients must not have myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or
                 with features suggestive of MDS/AML.
    
              -  Patient must not have had major surgery within 2 weeks of starting study treatments
                 and patients must have recovered from any effects of any major surgery.
    
              -  Patients must not have a history of uncontrolled ventricular arrhythmia, recent
                 (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable
                 spinal cord compression, superior vena cava syndrome, or extensive interstitial
                 bilateral lung disease on high resolution computed tomography (HRCT) scan.
    
              -  Patients must not have had previous allogenic bone marrow transplant or double
                 umbilical cord blood transplantation (dUCBT).
    
              -  Patients must not have had whole blood transfusions in the last 120 days prior to
                 randomization.
    
              -  Patients must be offered the opportunity to participate in specimen submission for
                 banking.
    
                   -  Note: Germline and somatic BRCA status will be evaluated using patient specimens
                      submitted as part of the correlative scientific studies and considered at the
                      time of study analysis, but this information will not be used for patient
                      selection or stratification.
    
              -  Patients must be informed of the investigational nature of this study and must sign
                 and give written informed consent in accordance with institutional and federal
                 guidelines.
    
              -  As a part of the OPEN registration process, the treating institution's identity is
                 provided in order to ensure that the current (within 365 days) date of institutional
                 review board approval for this study has been entered in the system.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Invasive Disease-Free Survival (IDFS)
    Time Frame:Up to 8 years
    Safety Issue:
    Description: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 and 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 Outcome Measures

    Measure:Locoregional Recurrence-Free Interval (Local Disease-Free Interval (LDFI))
    Time Frame:Up to 8 years
    Safety Issue:
    Description:Time from date of registration to date of invasive local or regional recurrence. Patients last known to be alive without recurrence are censored at their last contact date. Patients with distant recurrence, second primary cancer or death are censored at the time of that event. A competing risk framework will be conducted separating out the event types of locoregional recurrence from distant recurrence and death. 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.
    Measure:Distant Relapse-Free Survival (Distant Recurrence-Free Survival)
    Time Frame:Up to 8 years
    Safety Issue:
    Description:Time from date of registration to date of invasive distant disease recurrence, second invasive primary cancer (breast or not) or death due to any cause. Patients last known to be alive who have not experienced disease recurrence, or second primary cancer are censored at their last contact date.
    Measure:Overall Survival
    Time Frame:Up to 8 years
    Safety Issue:
    Description:Time from date of registration to date of death due to any cause. Patients last known to be alive are censored at their last contact date.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:National Cancer Institute (NCI)

    Trial Keywords

    • Inflammatory breast cancer
    • Olaparib
    • Radiation therapy

    Last Updated

    December 9, 2019