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Full Protocol
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CALGB 40502 - "A Randomized Phase III Trial of Weekly Paclitaxel Compared to Weekly Nanoparticle Albumin Bound NAB-Paclitaxel or Ixabepilone Combined with Bevacizumab as First-Line Therapy for Locally Recurrent or Metastatic Breast Cancer"
Treatment Plan (Supplied Drugs: Ixabepilone, Bevacizumab, & NAB-Paclitaxel)
ADMINISTER WEEKLY x 3 WKS FOLLOWED BY 1 WK REST
ARM A
Paclitaxel: 90mg/m2, IV over 1 hr, weekly on Days 1, 8, 15
Followed by:
Bevacizumab*: 10mg/kg, IV, Days 1 & 15 q cycle
ARM B
Nab-Paclitaxel: 150mg/m2, IV over 30 mins, weekly on Days 1, 8, 15
Followed by:
Bevacizumab*: 10mg/kg, IV, Days 1 & 15 q cycle
ARM C
Ixabepilone: 16mg/m2, IV over 1 hr, weekly on Days 1, 8, 15
Followed by:
Bevacizumab*: 10mg/kg, IV, Days 1 & 15 q cycle
* See protocol for IV duration instructions.
Restage q 2 cycles until disease progression. If CR, PR, or SD continue study tx until PD
Eligibility
Histol-confirmed invasive breast cancer.
Stage IV or IIIB disease (AJCC, 6th ed.), not amenable to local therapy.
No "currently active" 2nd malignancy except non-melanoma skin cancer. Not considered "currently active" if pt completed therapy & <30% risk of relapse (physician's opinion).
HER2+ pts are eligible if previously received Trastuzumab or Lapatinib. Progression on HER2 directed therapy not required. HER2/neu status must be known at regist.
ER & PgR status must be known at regist. ER &/or PgR >1% cells are considered positive.
Age >18.
Prior adjuv or neoadjuv taxane is allowed, if >12 mos from completion of adjuv therapy & disease recurrence.
No prior chemo regimens for mets or locally adv breast cancer.
Prior RT must be completed >2wks pre-study entry.
Tx w/bisphosphonates is allowed & recommended per ASCO guidelines.
Prior Trastuzumab or Lapatinib is required for pts w/HER2 overexpressing tumors.
Prior Bevacizumab is allowed.
No major surgery, open bx, or significant traumatic injury w/i 28 days pre-study regist & must be fully recovered.
No anticipated need for major surgery during study course.
No core bx or other minor surgery w/i 7 days pre-study regist (doesn't include placement of vascular access device).
Must have meas disease (target lesions) - defined as >1 lesion that can be accurately meas in 1 dimension (longest diameter to be recorded) as >2cm by conventional techniques or >1cm by spiral CT. Non-meas lesions include bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusion, inflammatory breast disease, lymphangitis cutis/pulmonitis, abdominal masses not confirmed & followed by imaging techniques, & cystic lesions.
No pre-existing perip neuropathy >Grade 2.
Zubrod perf status 0-1.
No pregnant or nursing women. Negative serum or urine b-Hcg prior to starting study tx (if applicable).
No CTCAE Grade >3 hypersensitivity to Paclitaxel or Cremophor EL.
No abdominal fistula or intra-abdominal abscess w/i 6 mos pre-study regist.
No GI perforation w/i 12 mos pre-regist.
No significant bleeding episodes w/i 6 mos pre-regist.
No hx of clinically significant cardiovascular disease, including:
Uncontrolled HTN (systolic >150 &/or diastolic >90 on antihypertensive meds) or any prior hx of hypertensive crisis or hypertensive encephalopathy.
MI or unstable angina w/i past 6 mos
NHYA CHF >Grade 2
Symptomatic perip vascular disease
Significant vascular disease or arterial thrombotic events
Pts on full-dose anticoagulants must be on stable dose of warfarin or LMW heparin. Pts receiving anti-platelet, on daily prophylactic dose aspirin, or receiving stable doses of anticoagulation for atrial fib are eligible.
No stroke or TIA w/i 6 mos pre-study regist.
If hx of seizures, must be well controlled w/standard meds.
No progressing or untreated CNS mets or leptomeningeal disease. Pts w/resected brain mets, gamma knife radiosurgery, or whole brain RT and having stable MRI scans x 3 mos (including w/i 4 wks of study start) are eligible.
No serious, non-healing wound, ulcer, or bone fx.
Life expectancy >12 wks.
Initial lab values: Granulocytes >1500/ul; platelets >100,000/ul; creat <2.0mg/dL; bili <1.5mg/dL (unless due to Gilbert's syndrome); SGOT, SGPT <2.5x ULN; serum or urine b-Hcg negative (if applicable); UA <1+ protein (if >2+ proteinuria at baseline, must undergo a 24-hr urine collection showing <1g of protein/24 hrs or UPC <1 ratio to be eligible).
PRESTUDY REQUIREMENTS:
Within 14 days pre-regist: All bloodwork, urine for proteinuria, H&P
Within 28 days pre-regist: Any xray, scan, or US used for tumor msmt; CT chest/abdomen/pelvis, bone scan
H&P, progress notes, pulse, BP, ht, wt, BSA, perf status
Tumor msmts
ER/PgR & HER2/neu status (required pre-regist)
Drug Toxicity Asmt**
CBC/diff/platelets
Serum creat/BUN
Serum lytes, Ca++
SGOT, SGPT, bili
Serum or urine b-Hcg negative (if applicable)
INR/PT
UA - check urine protein
CXR (PA & Lat) - not required if CT chest obtained
CT/Spiral CT Chest/Abdomen/Pelvis (preferred) or MRI
Bone scan w/CT w/bone windows*
Whole blood (w/pt's consent)**#
1 FFPE block**##
* Bone scan required for all pts for determination of mets bone disease. CT w/bone windows only for pts w/bone mets.
** Prior to initiation of therapy.
# For circulating tumor cells (CTC), circulating endothelial cells (CEC), serum caveolin, & pharmacogenetics. See protocol for collection details. Ship CTC & CEC at ambient temp same day as collected by overnight delivery to: Janet Scott, PhD; c/o Park Laboratory; San Francisco, CA. Ship both serum caveolin (frozen on dry ice) & pharmacogenetics (on cold pack) by overnight delivery to: CALGB Path Coordinating Office; Columbus, OH. Contact KCCOP for CTC Cell Saver tube kits.
## For SPARC, taxane resistance markers, & caveolin mutations. Submit after regist to: CALGB Path Coordinating Office; Columbus, OH. If bx was performed to diagnose advanced disease, the block should also be provided.
Signed informed consent.