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

NCT03173976 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 201610743
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this single arm open label phase 1b clinical study is to see what effect zoledronic acid has on tumors in patients with resectable any grade chondrosarcoma prior to surgery.

Conditions

Chondrosarcoma

Outcome Measures

Primary Outcomes (2)

• Phase 1b cohort: Dose Limiting Toxicity - to examine the toxicity related to the therapy by measuring the number of treatment related adverse events in patients

  Toxicity will be assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 4.0 (CTCAEv4.)

  All eligible patients that have initiated treatment will be considered evaluable for assessing adverse event rate(s) up to 4 weeks post Cycle 2

• Expansion cohort: Response Rate - Change at evaluations

  Response and progression will be assessed by tumor viability, osteoclast activity, and bone destruction compared to the initial biopsy in subjects with localized any grade chondrosarcoma.

  Changes on 2 consecutive evaluations at screening phase (days 1-14); Cycle 2 at 3 weeks post operatively; EOT visit at 4 weeks post Cycle 2; and then at follow up visits every 6 months for up to 5 years.

Secondary Outcomes (2)

• Recurrence (local or metastatic) free survival

  All eligible patients that have initiated treatment will be considered evaluable for assessing recurrence free survival for up to 2 years.

• Overall survival

  All eligible patients that have initiated treatment will be considered evaluable for assessing overall survival up to 5 years.

Study Arms (1)

Zoledronic Acid

EXPERIMENTAL

1 cycle of Zoledronic Acid (ZA) at 4mg IVP prior to surgery and a second cycle of ZA at 4 mg IVP 3 weeks after surgery

Drug: Zoledronic Acid

Interventions

Zoledronic Acid DRUG

Zoledronic acid, a member of bisphosphonate class, inhibits bone resorption.

Also known as: Zometa®

Zoledronic Acid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged \>/= 18 years old
• ECOG Performance Status of \</= 2
• 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
• Patients must meet the following laboratory criteria:
• Hematology:
• Neutrophil count of \>1500/mm
• Platelet count of \> 100,000/mm3
• Hemoglobin \&#8805; 9 g/dL
• 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

You may not qualify if:

• 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 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).

Sponsors & Collaborators

• Mohammed Milhem: lead
• Rising Tide Foundation: collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Chondrosarcoma

Interventions

Zoledronic Acid

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mohammed Milhem, MBBS

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor Hematology/Oncology

Model Details: This is a single arm open label phase 1b clinical trial assessing the safety and efficacy of neoadjuvant zoledronic acid in patients with resectable any grade chondrosarcoma as measured by pathological characteristics and recurrence free survival.

Study Record Dates

• First Submitted: May 29, 2017
• First Posted: June 2, 2017
• Study Start: July 18, 2017
• Primary Completion: April 20, 2023
• Study Completion (Estimated): May 1, 2028
• Last Updated: November 6, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)