NCI Community Oncology Research Program - Protocol Summary
SWOG S1207 - "Phase III Randomized, Placebo-Controlled Clinical Trial Evaluating the Use of Adjuvant Endocrine Therapy +/- One Year of Everolimus in Patients with High-Risk, Hormone Receptor-Positive and HER2/neu Negative Breast Cancer (E3 Breast Cancer Study - Evaluating Everolimus with Endocrine Therapy)"
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 KCCOP for complete protocol information.
Breast Clinical Trial
CANCER TYPE: Stage II
RESEARCH BASE: SWOG S1207
NCT NUMBER: 01674140
HIPPA FORM: DOWNLOAD HIPPA FORM
Consent Form: VIEW CONSENT FORM
Adj., Stgs I-III, high-risk, ER &/or PgR+, HER2(-); Endocrine therapy + Everolimus/placebo. DCP-001 Eligible
Treatment Plan (Supplied Drug: Everolimus/placebo)
REGISTRATION / RANDOMIZATION
Everolimus / placebo: 10mg, PO, QD (preferably am), x 378 days
Endocrine therapy: Choice of therapy dependent on menopausal status & patient/physician preference (see §7.2), x >5 yrs
Blood specimens for the BAHO substudy are no longer required as of 10-15-15
- Histol-confirmed invasive breast carcinoma, ER+ &/or PgR+, HER2(-). Standard adjuv endocrine therapy must be planned. ER+ &/or PgR+ by ASCO/CAP guidelines >1% positive nuclear staining. HER2 by ASCO/CAP guidelines using IHC,ISH or both (if IHC 2+, an eval for gene amplification must be done and not amplified).
- No mets (Stg IV) breast cancer. Multifocal, multicentric, synchronous bilat, & prim inflammatory breast cancers are allowed (see protocol definitions).
- Must be high-risk, by one of following:
- Completion of adjuv chemo & pathologically negative lymph nodes (LN), tumor >2cm in greatest diameter, & Oncotype DX Recurrence Score >25 (completed as standard of care). Patients with micrometastases as the only nodal involvement (pN1mi) are eligible, and will be categorized as node-negative.
- Completion of adjuv chemo & pathologically 1-3 positive LNs, & either Oncotype DX Recurrence Score >25 (screened via SWOG S1007 or otherwise) or tumor tissue w/path Grade III following local practice.
- Completion of adjuv chemo & pathologically >4 positive LNs.
- Completion of neoadjuv chemo & pathologically >1 positive LN, determined pre- or post-chemo.
- NOTE: In the lymph node positive groups, at least one metastasis ≥ 2.0 mm must be present. Patients with micrometastases as the only nodal involvement (pN1mi) are eligible and will be categorized as node-negative.
- Completed breast-conserving surgery or total mastectomy, w/negative margins (no tumor or DCIS at resection line) & appropriate axillary staging. Additional operative procedures may be done to obtain clear margins.
- If breast-conserving surgery, must have completed whole breast RT. Use of regional nodal basin RT at investigator's discretion.
- If >4 positive LNs, must have completed breast/chest wall & nodal basin RT pre-randomiz.
- Registered >21 days post-RT completion & recovered <Grade 1 from any RT effects.
- Must have undergone axillary stating by sentinel node bx or axillary lymph node dissection (ALND).
- If 1-3 positive LNs, sentinel node bx alone is allowed if pt completed either whole breast or chest wall RT & prim tumor <5cm.
- All pts w/>4 positive LNs must have completed ALND (w/ or w/o prior sentinel node bx).
- Completed standard neoadjuv or adjuv taxane &/or anthracycline-based chemo pre-randomiz. Should include >4 cycles. Register w/i 42 wks post chemo completion. May have started endocrine therapy at any time after dx of current breast cancer.
- No current or planned Trastuzumab. Concurrent bisphosphonate therapy is allowed. No prior mTOR inhibitors. No prior investigational drug w/i 28 days, and no other planned investigational drug for study duration.
- Within 28 days pre-regist: ANC >1500/mL; Hgb >9g/dL, platelets >100,000/mL; bili <1.5mg/dL (or <3.0mg/dL if due to Gilbert's Syndrome); SGOT, SGPT, & alk phos each <1.5x IULN; serum creat <IULN; fasting cholesterol <300mg/dl; triglycerides <2.5x IULN (lipid lowering agents allowed to reach these values).
- Zubrod 0-2.
- No >Grade III cardiac disease by NYHA criteria, unstable angina pectoris, MI w/i past 6 mos, or serious uncontrolled cardiac arrhythmia.
- If previously diagnosed w/diabetes, must not have uncontrolled diabetes (Hg A1c >7%) w/i 28 days pre-regist.
- No organ allograft or other prior immune compromise. No use of chronic, systemic corticosteroids/other immunosuppressive agents. Topical or inhaled steroids are allowed.
- HIV+ pts may be enrolled if baseline CD4 >500 cells/mm3 & not taking anti-retroviral therapy. Patients with known hepatitis are not eligible unless there is a known negative hepatitis panel. Patients must not have any known uncontrolled underlying pulmonary disease.
- Able to take PO meds. No impairment of GI function or GI disease significantly altering the absorption of blinded drug.
- No immunization w/attenuated live vaccine w/i 7 days pre-regist, or plans to receive such vaccine while on protocol tx.
- No CYP3A4 inhibitors &/or inducers w/i 14 days pre-regist, or plans to take while on protocol tx.
- No other prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, or other cancer disease-free >5 yrs.
- No pregnant or nursing women. Women/Men of reproductive potential must use effective, non-hormonal contraception.
- Must be offered participation in the Behavioral & Health Outcomes Study (BAHO). Pts who have already started endocrine therapy are eligible for the BAHO study.
- PRE-STUDY REQUIREMENTS:
- H&P, ht, wt, perf status within 28 days prior to registration
- BAHO questionnaire
- Serum creat
- Alk phos
- Fasting cholesterol & triglycerides
- Tissue for correlative studies & banking (MANDATORY)*
- Blood for correlative studies & banking (MANDATORY)**
- Signed informed consent.
* Preferably paraffin block, positive LN block, & negative LN block (punch bx [2nd choice] or 20 slides [3rd choice]) may be substituted. With patient consent, residuals will be banked for future research.
** 7.5mL whole blood in lavender top EDTA Vacutainer tube & 10mL whole blood in red-top or SST Vacutainer tube.