Anti-Osteoclast Therapy as Neoadjuvant in Treatment of Chondrosarcoma - Phase 1b Trial

1. Male or female patients aged >/= 18 years old
2. ECOG Performance Status of \</= 2
3. Written informed consent from subject or the subject's legally authorized representative, obtained prior to participation in the study and any related procedures being performed

4. Patients must meet the following laboratory criteria:

   1. Hematology:

      • Neutrophil count of >1500/mm
      • Platelet count of > 100,000/mm3
      • Hemoglobin \≥ 9 g/dL

   2. Biochemistry:

      • AST/SGOT and ALT/SGPT \</=2.5 x upper limit of normal (ULN) or \</=5.0 x ULN if the transaminase elevation is due to disease involvement
      • Serum bilirubin \</= 1.5 x ULN; for subjects with Gilbert's syndrome, direct bilirubin \</=1.5×ULN and indirect bilirubin \</=3×ULN
      • Serum creatinine \</= 1.5 x ULN or estimated creatinine clearance >/= 50 ml/min by Cockcroft-Gault equation: GFR=(140-age)*(wt in kg)*(0.85 if female)/(72xCr)
      • Total serum calcium (corrected for serum albumin) >/= 8.5 mg/dL or ionized calcium >/= 3.8 mg/dL
      • Serum potassium >/= LLN
      • Serum sodium >/= LLN
      • Serum albumin >/= 3g/dl
5. Any patient with a biopsy proven diagnosis of chondrosarcoma that is grade I, II or III or in cases where histological and radiological correlation suggests low grade chondrosarcoma as per multidisciplinary discussion.
6. Patients with biopsy proven dedifferentiated chondrosarcoma that chose not to pursue neoadjuvant chemotherapy are allowed.
7. Patients must not have received zoledronic acid (ZA) for any reason prior to the study.
8. Patients with metastatic disease are allowed, if indication to remove primary tumor.

Exclusion criteria

1. Prior use of Osteoclast inhibitors for osteoporosis within 6 months from screening will not be allowed.
2. Impaired cardiac function
3. Uncontrolled hypertension
4. Creatinine >1.5 or history of Renal disease preventing use of ZA.
5. Other concurrent severe and/or uncontrolled medical conditions including need for urgent dentoalveolar surgery as indicated by preventative dental exam
6. Concomitant use of any anti-cancer therapy or radiation therapy
7. Women who are pregnant or breast feeding or WOCBP not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months).