CALGB 70604 - "A Randomized, Phase III Study of Standard Dosing versus Longer Dosing Interval of Zoledronic Acid in Metastatic Cancer"

Treatment Plan    (Supplied Drug:  None)

ARM A

Zoledronic Acid*:  4mg, IV over >15 mins, q 4 wks x 2 yrs (or until unacceptable toxicity)

ARM B

Zoledronic Acid*:  4mg, IV over >15 mins, q 12 wks x 2 yrs (or until unacceptable toxicity)

*  Starting dose adjusted according to calc CrCl (Cockroft-Gault formula).  All pts should take 500mg elemental calcium, PO, QD & 400-800 IU Vit D, PO, QD (single products, combination, or as part of a multivitamin).

Eligibility

• Histol confirmation of breast adenocarcinoma, prostate adenocarcinoma, or multiple myeloma.

• >1 site of bone mets or bone involvement by radiologic imaging (plain xray, CT, PET, PET/CT, MRI, bone scan, or skeletal survey).  Indeterminate lesions should be confirmed by 2nd imaging method.

• No prior IV bisphosphonates.  PO bisphosphonates are allowed if discontinued prior to start of protocol therapy.

• No prior Denosumab.

• No prior radiopharmaceuticals.   Radioactive iodine is allowed.  Prostate cancer pts treated w/brachytherapy are allowed.

• Prior RT to bone is allowed if >1 site of bone mets that has not been irradiated & RT is complete pre-regist.  Must be no plan for RT to non-irradiated sites of bone mets.

• Prior adjuv & mets chemo, biologic therapy, & endocrine therapy is allowed.

• No current tx w/investigational agent(s).  See protocol for allowed therapies & concurrent enrollment to other clinical trials.

• No known brain mets.  Pts who develop brain mets during the study can continue tx as assigned.

• No pregnant or nursing women.

• ECOG perf status 0-2.

• Age >18.

• Initial lab values:   Calc CrCl >30mL/min (Cockroft-Gault formula); corrected serum calcium (using standard institutional practices) >8.0mg/dL & <11.6mg/dL.

• PRESTUDY REQUIREMENTS:

  Within 16 days pre-regist:  H&P, all bloodwork

  Within 12 wks pre-regist:  Imaging to document bone mets

  • PE, pulse, BP, ht, wt

  • Brief Pain Index

  • ONJ screening (questions found on On-Study Form)

  • CBC/diff/platelets

  • Serum creat

  • Serum calcium

  • Albumin

  • Pregnancy test (if applicable)

  • Imaging studies*

  • Correlative study (optional, but MUST be asked to participate)**

  *       Must have >1 site of bone involvement which has not been irradiated.  May use plain xray, PET, PET/CT, bone scan, CT, MRI, or skeletal survey (confirm indeterminate lesions by 2nd imaging method).

  **      Whole blood for pharmacogenomic studies:  10mL perip venous blood in EDTA purple top tube.  Contact KCCOP for CALGB's FedEx acct #.  Process per protocol & refrigerate until shipped.  Ship same day as drawn (Mon-Fri via overnight delivery to CALGB Path Coord Office).

• Signed informed consent.