SWOG S0307 - "Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer"

Treatment Plan    (Supplied Drugs:  Zoledronic Acid, Clodronate, Ibandronate)

Arm 1

Zoledronic Acid:  4mg, IV, q month x 6 mos (then q 3 mos x 2.5 yrs)

Arm 2

Clodronate:  1600mg, PO, QD, x 3 yrs

Arm 3

Ibandronate:  50mg, PO, QD, x 3 yrs

Eligibility

• Women w/histol-confirmed primary invasive breast adenocarcinoma (Stg I, II, III) w/no mets.  Prim disease w/i breast must be resected w/mastectomy or breast sparing surgery.  Axillary node eval should be performed.

• Must receive standard (systemic) adjuv therapy for breast cancer.  Chemo, hormone therapy, or combined chemo/hormone therapy is allowed.  Additional therapies are allowed including RT & biologic agents.  No pts who receive biologic agents only or local RT only (w/o chemo &/or hormone therapy).  Pts who are at such a low risk of recurrence that adjuv therapy will not be prescribed are ineligible.  Neoadjuv therapy is permitted, but enrollment must occur after completion of surgery.

• May be enrolled prior to, simultaneously with, or after beginning adjuv systemic therapy.  Pts receiving hormone therapy alone or pre-op chemo should be enrolled w/i 84 days after date of final surgical procedure.  Pts receiving adjuv post-op chemo may be enrolled <8 wks after completion of chemo.  Additional biological therapy or RT is allowed at any time b/f or after regist.

• Encouraged to seek pt consent to submit tissue and serum for banking.  Written informed consent must be obtained prior to submitting samples.

• Zubrod 0-2.

• Must NOT be co-enrolled on protocols having bone density as an endpoint (i.e., CTSU NCIC MA.27).  Enrollment on other locoregional or systemic therapy breast cancer studies is allowed.

• Serum creat <2x IULN & calc CrCl >30ml/min w/i 7 days pre-enrollment.  No renal failure.

• Previous or current tx w/bisphosphonates for bone density is allowed, if bisphosphonante is discontinued at regist. 

• Dental exam w/i 6 mos prior to tx initiation.

• Skeletal pain is allowable if bone scan &/or roentgenological exam fails to disclose mets.  Suspicious findings must be confirmed benign by xray, MRI, or bx.

• No hx of esophageal stricture or motility disorders.  Hx of GERD pts are allowed.

• No pregnant or nursing women.  Women of reproductive potential must use effective contraception.  Negative pregnancy test (if applicable) w/ii 24-72 hrs prior to initiation of tx.

• No other prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, adequately treated Stg I or II cancer currently in complete remission, or any other cancer disease-free > 5 yrs.

• PRESTUDY REQUIREMENTS:

  • H&P, ht, wt, perf status

  • Disease asmt

  • Dental exam

  • CBC/diff/platelets*

  • Ca, PO4, Mg, albumin (albumin needed only if serum Ca drawn; not needed for ionized Ca)*

  • Na, K, Cl, HCO₃*

  • LFTs (SGOT or SGPT, bili, alk phos)*

  • Serum creat (w/i 7 days pre-regist)

  • Calc CrCl

  • Pregnancy test (if applicable, w/i 24-72 hrs prior to initiation of tx)

  • CXR*

  • Bone scan or roentgenological exam (if bone pain)*

  • CT chest & abdomen*

  • Tumor block for PTHrP & banking**

  • Serum for N-telopeptide & banking***

  *     Suggested for good medical practice

  **   Block or punch of block + 25 unstained 5 micron sections on slides.  Submit to:  Lab #107; SWOG Solid Tumor Tissue Bank; Univ. of Cincinnati; Cincinnati, OH.

  ***  10mL red-top.  Ship w/i 24 hrs w/cold pack to:  Lab #107; SWOG Solid Tumor Tissue Bank; Univ. of Cincinnati; Cincinnati, OH.

• Signed informed consent.