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

January 11, 2024 updated by: Mohammed Milhem
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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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. Prior to surgery, subjects will receive 1 standard dose of IV zoledronic acid given over 15 minutes. Surgery will be performed 21-31 days after the dose as per standard of care. The second standard dose of zoledronic acid will be given 3 weeks after surgery.

Phase 1b:

The Phase 1b portion of this study is to ensure the safety and tolerability of standard dose of zoledronic acid intravenously as assessed by incidence of dose limiting toxicities (DLT). Although the safety of use of this drug has been established in patients with bone metastases from solid tumors (breast, prostate) and in patients with hypercalcemia of malignancy and multiple myeloma, it has not been tested in patients with chondrosarcoma. Surgery will be performed between day 21 to 31 from the dose of zoledronic acid to allow its effect on the tumor and resolution of toxicities. A total of 6 patients will be enrolled in this run-in phase 1b. Patients will be followed post operatively as per NCCN guidelines with local and systemic imaging.

Expansion Cohort:

The phase 1b expansion cohort of the study will provide an estimate of the relative treatment effect of zoledronic acid on any grade chondrosarcoma specimens. Subjects will receive a total of 2 doses of zoledronic acid, one dose prior to surgery and the second dose 21 days after surgery. Patients will undergo standard of care surgery 21-31 days from the first dose of zoledronic acid. 9 subjects will be enrolled in this cohort for a total of 15 planned subject enrollment over 3 years. Patients will be followed post operatively for recurrence with imaging and survival and as per NCCN guidelines.

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zoledronic Acid
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
Zoledronic acid, a member of bisphosphonate class, inhibits bone resorption.
Other Names:
  • Zometa®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: All eligible patients that have initiated treatment will be considered evaluable for assessing adverse event rate(s) up to 4 weeks post Cycle 2
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
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence (local or metastatic) free survival
Time Frame: All eligible patients that have initiated treatment will be considered evaluable for assessing recurrence free survival for up to 2 years.
Recurrence-free survival will be estimated using the Kaplan-Meier method.
All eligible patients that have initiated treatment will be considered evaluable for assessing recurrence free survival for up to 2 years.
Overall survival
Time Frame: All eligible patients that have initiated treatment will be considered evaluable for assessing overall survival up to 5 years.
Overall survival will be estimated using the Kaplan-Meier method.
All eligible patients that have initiated treatment will be considered evaluable for assessing overall survival up to 5 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Investigators

  • Principal Investigator: Mohammed Milhem, MBBS, University of Iowa

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 18, 2017

Primary Completion (Estimated)

July 1, 2024

Study Completion (Estimated)

July 1, 2024

Study Registration Dates

First Submitted

May 29, 2017

First Submitted That Met QC Criteria

May 29, 2017

First Posted (Actual)

June 2, 2017

Study Record Updates

Last Update Posted (Actual)

January 12, 2024

Last Update Submitted That Met QC Criteria

January 11, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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