Zoledronic Acid before and after Surgery in Treating Patients with Grade I-III Chondrosarcoma
This phase Ib trial studies the side effects and how well zoledronic acid works before and after surgery in treating patients with grade I-III chondrosarcoma. Zoledronic acid may be an effective treatment for chondrosarcoma and cause less severe side effects.
Inclusion Criteria
- Male or female patients aged >= 18 years old
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- Written informed consent obtained from subject or the subject’s legally authorized representative prior to participation in the study and any related procedures being performed
- Neutrophil count of > 1500/mm^3
- Platelet count of > 100,000/mm^3
- Hemoglobin >= 9 g/dL
- Aspartate aminotransferase(AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (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 x ULN and indirect bilirubin =< 3 x ULN
- Serum creatinine =< 1.5 x ULN or estimated creatinine clearance >= 50 ml/min by Cockcroft-Gault equation
- Total serum calcium (corrected for serum albumin) >= 8.5 mg/dL or ionized calcium >= 3.8 mg/dL
- Serum potassium >= lower limit of normal (LLN)
- Serum sodium >= LLN
- Serum albumin >= 3 g/dl
- 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
- Patients with biopsy proven dedifferentiated chondrosarcoma that chose not to pursue neoadjuvant chemotherapy are allowed
- Patients must not have received zoledronic acid (ZA) for any reason prior to the study
- Patients with metastatic disease are allowed, if indication to remove primary tumor
Exclusion Criteria
- Prior use of osteoclast inhibitors for osteoporosis within 6 months from screening will not be allowed
- Impaired cardiac function
- Uncontrolled hypertension
- Creatinine > 1.5 or history of renal disease preventing use of ZA
- Other concurrent severe and/or uncontrolled medical conditions including need for urgent dentoalveolar surgery as indicated by preventative dental exam
- Concomitant use of any anti-cancer therapy or radiation therapy
- Women who are pregnant or breast feeding or women of child bearing potential (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)
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03173976.
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of neoadjuvant zoledronic acid as assessed by incidence of dose-limiting toxicities (DLT) in subjects with localized any grade chondrosarcoma. (Phase Ib)
II. To estimate the efficacy of neoadjuvant zoledronic acid as assessed by tumor viability, osteoclast activity, and bone destruction compared to the initial biopsy in subjects with localized any grade chondrosarcoma. (Expansion Cohort)
SECONDARY OBJECTIVES:
I. Recurrence (local or metastatic) free survival at 2 years.
II. Overall survival at 5 years.
OUTLINE:
Patients receive zoledronic acid intravenously (IV) over 15 minutes on day 1 of cycle 1. Beginning 21-31 days after dose of zoledronic acid, patients undergo surgery. Beginning 3 weeks after surgery, patients then receive zoledronic acid IV over 15 minutes on day 1 of cycle 2. Treatment with zoledronic acid repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months for 5 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationUniversity of Iowa/Holden Comprehensive Cancer Center
Principal InvestigatorMohammed M. Milhem
- Primary ID201610743
- Secondary IDsNCI-2017-01355
- ClinicalTrials.gov IDNCT03173976