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 NCORP-KC for complete protocol information.

Breast Clinical Trial

BRIEF DESCRIPTION

Adj., Stgs I-III, high-risk, ER &/or PgR+, HER2(-); Endocrine therapy + Everolimus/placebo.  DCP-001 Eligible

NOTES

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

ELIGIBILITY

• 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 HER-2 IHC is 2+, evaluation for
  gene amplification (ISH) must be performed and the ISH must be negative; ISH is not
  required if IHC is 0 or 1+, but must be negative if performed).
• 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 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.
  • Patients who receive radiation therapy must have completed radiation therapy at least 21 days prior to registration.
• 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
  • CBC/diff/platelets
  • Serum creat
  • Bili
  • SGOT/SGPT
  • 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.