NCI Community Oncology Research Program - Protocol Summary
NSABP B-55 - "A Randomised, Double-Blind, Parallel Group, Placebo-Controlled Multi-Centre Phase III Study to Assess the Efficacy and Safety of Olaparib Versus Placebo as Adjuvant Treatment in Patients with Germline BRCA1/2 Mutations and High Risk HER2 Negative Primary Breast Cancer Who Have Completed Definitive Local Treatment and Neoadjuvant or Adjuvant Chemotherapy"
The summary below serves as a brief review of the treatment plan and eligibility for the protocol.
This summary is not intended to be used in place of the full eligibility & treatment information in the protocol.
Please contact NCORP-KC for complete protocol information.
Breast Clinical Trial
CANCER TYPE: Stage I
RESEARCH BASE: NRG/NSABP
NCT NUMBER: NCT02032823
HIPPA FORM: DOWNLOAD HIPPA FORM
Consent Form: VIEW CONSENT FORM
UPDATED ON 09/19/2018 (20:00:55)
High risk, TNBC, BRCA1 or BRCA2 positive mutation, Stage I-III, Olaparib vs Placebo post definitive local tx and chemo. DCP-001 Eligible
Treatment Plan (Supplied Drug: Olaparib)
Randomization within 8 weeks after last treatment (surgery, chemo, radiation)
Olaparib 300mg orally twice daily for 12 months
Placebo orally twice daily for 12 months
- Signed informed consent
- Female or male ≥18 years of age
- Histologically confirmed non-metastatic primary triple negative invasive adenocarcinoma of the breast that is at surgery:
- either axillary node-positive (any tumour size) or axillary node-negative with primary tumour > 2cm for patients who received adjuvant chemotherapy
- or showing evidence of non pCR for patients who received neoadjuvant chemotherapy
- Invasive TNBC defined as:
- ER and PR negative (not eligible for endocrine therapy) defined as IHC nuclear staining <1% AND
- HER2 negative (not eligible for anti-HER2 therapy) defined as:
- IHC 0, 1+ without ISH OR
- IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported average HER2 copy number < 6 signals/cells OR
- ISH non-amplified with ratio less than 2.0 and if reported average HER2 copy number < 6 signals/cells without IHC)
- Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). Patients with BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g., “Variants of uncertain clinical significance” or “Variant of unknown significance” or “Variant, favour polymorphism” or “benign polymorphism” etc.) are not eligible.
- Completed adequate breast and axilla surgery defined as:
- The inked margins of breast conservation surgery or mastectomy must be histologically free of invasive breast cancer and ductal carcinoma in situ with the exception of the posterior margin if this margin is the pectoralis major fascia or the anterior margin if this is the dermis. Patients with resection margins positive for lobular carcinoma in situ are eligible.
- Patients with breast conservation must have adjuvant radiotherapy. Patients having mastectomy should have adjuvant radiotherapy according to international guidelines (St Gallen/ASCO/ESTRO).
- Adjuvant group: Sentinel lymph node biopsy alone if negative or if lymph node(s) only contain micrometastases (≤2.0 mm) OR positive sentinel lymph node biopsy followed by axillary node clearance or axillary nodal radiotherapy
- Neoadjuvant group:
- If sentinel lymph node biopsy before neoadjuvant chemotherapy: sentinel lymph node biopsy alone if negative or if lymph node(s) only contain micrometastases (≤2.0 mm) OR positive sentinel lymph node biopsy followed by axillary node clearance or axillary nodal radiotherapy following completion of neoadjuvant chemotherapy
- If sentinel lymph node biopsy after neoadjuvant chemotherapy: Sentinel lymph node biopsy alone if negative OR positive sentinel lymph node biopsy followed by axillary node clearance.
- Completed at least 6 cycles neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes or the combination of both. Prior platinum as potentially curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant treatment for breast cancer is allowed
- Patients must have normal organ and bone marrow function measured within 28 days prior to randomization as defined below:
- Hemoglobin ≥ 10.0 g/dL with no blood transfusions in the past 28 days
- ANC ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Total Bilirubin ≤ ULN (institutional upper limit of normal) except elevated total bilirubin <1.5 x ULN due to Gilbert’s disease or similar syndrome involving slow conjugation of bilirubin
- Serum creatinine ≤ 1.5 x ULN
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN
- ALP ≤ 2.5 x ULN
- Patients with screening ALT/AST or ALP above institutional upper limit of normal should have liver ultrasound or CT/ MRI prior to randomisation. Screening bone scan is required if ALP and/or corrected calcium level are above the institutional upper limit. (Note PET CT scan may be used as an alternative imaging techniques).
- ECOG performance status 0-1
- *Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 7 days prior to randomisation
Postmenopausal is defined as:
- Age ≥ 60 yrs
- Age < 60 and amenorrheic for 1 year or more in the absence of chemotherapy and/or hormonal treatment
- FSH and plasma oestradiol levels in the post menopausal range for women under 60
- radiation-induced oophorectomy with last menses >1 year ago
- or surgical sterilisation (bilateral oophorectomy)
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
- Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary tumour, mandatory. If tumour is not available, approval by Study Team for patient's entry into the trial is required.
- No exposure to an investigational product within 30 days or five half lives (whichever is the longer) prior to randomization.
- No previous treatment with a PARP inhibitor, including olaparib and/or known hypersensitivity to any of the excipients of study treatment.
- No patients with second primary cancer, EXCEPTIONS: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal Carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 years prior to randomisation. More than one course of chemotherapy for previous malignancies (e.g: breast cancer or ovarian cancer > 5 years ago treated with adjuvant chemotherapy)
- No resting ECG with QTc > 470 msec detected on 2 or more time points within a 24 hour period or family history of long QT syndrome. If ECG demonstrates QTc >470 msec, patient will be eligible only if repeat ECG demonstrates QTc ≤470 msec.
- No patients receiving systemic chemotherapy within 3 weeks prior to start of study treatment.
- No patients receiving adjuvant radiotherapy within 2 weeks prior to start of study treatment.
- No concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
- No persistent toxicities (≥CTCAE grade 2) caused by previous cancer therapy, excluding alopecia and CTCAE grade 2 peripheral neuropathy.
- No patients with myelodysplastic syndrome/ treatment related acute myeloid leukaemia (t-AML).
- No major surgery within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery.
- No patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, extensive bilateral lung disease on High Resolution Computed Tomography scan or any psychiatric disorder that prohibits obtaining informed consent.
- Patients must be able to swallow orally administered medication and not have gastrointestinal disorders likely to interfere with absorption of the study medication.
- Must not be pregnant or breastfeeding.
- Must not have known active Hepatitis B or C.
- No patients known to be HIV positive with one or more of the following:
a. Baseline CD4 count of < 250 cells/mm3
b. History of AIDS indicator conditions
c. Anti-retroviral therapy with any potent CYP3A4 inhibitor
- No previous allogeneic bone marrow transplant.
- No whole blood transfusions in the last 120 days prior to entry to the study which may interfere with gBRCA testing (packed red blood cells and platelet transfusions are acceptable, for timing refer to inclusion criteria no.8).