Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03598257
Recruitment Status : Recruiting
First Posted : July 25, 2018
Last Update Posted : October 15, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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 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.

Condition or disease Intervention/treatment Phase
Inflammatory Breast Carcinoma Drug: Olaparib Radiation: Radiation Therapy Phase 2

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Randomized Trial of Olaparib (NSC-747856) Administered Concurrently With Radiotherapy Versus Radiotherapy Alone for Inflammatory Breast Cancer
Actual Study Start Date : September 12, 2018
Estimated Primary Completion Date : July 31, 2023
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Olaparib

Arm Intervention/treatment
Experimental: Group I (olaparib, radiation therapy)
Participants 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.
Drug: Olaparib
Given PO
Other Names:
  • AZD 2281
  • AZD-2281
  • AZD2281
  • KU-0059436
  • Lynparza
  • PARP Inhibitor AZD2281

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • irradiated
  • Irradiation
  • Radiation
  • Radiotherapeutics
  • radiotherapy
  • RT
  • Therapy, Radiation

Active Comparator: Group II (radiation therapy)
Participants undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unaccepted toxicity
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • irradiated
  • Irradiation
  • Radiation
  • Radiotherapeutics
  • radiotherapy
  • RT
  • Therapy, Radiation




Primary Outcome Measures :
  1. 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 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 :
  1. Locoregional Recurrence-Free Interval (Local Disease-Free Interval (LDFI)) [ Time Frame: Up to 8 years ]
    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.

  2. Distant Relapse-Free Survival (Distant Recurrence-Free Survival) [ Time Frame: Up to 8 years ]
    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.

  3. Overall Survival [ Time Frame: Up to 8 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03598257


  Show 94 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Reshma Jagsi Southwest Oncology Group

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03598257     History of Changes
Other Study ID Numbers: NCI-2018-01519
NCI-2018-01519 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1706 ( Other Identifier: SWOG )
S1706 ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
First Posted: July 25, 2018    Key Record Dates
Last Update Posted: October 15, 2019
Last Verified: July 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Cancer Institute (NCI):
Inflammatory breast cancer
Olaparib
Radiation therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Inflammatory Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents