ChondrosarcomaPhase 1NCT03173976
Anti-Osteoclast Therapy as Neoadjuvant in Treatment of Chondrosarcoma - Phase 1b Trial
A Phase 1 study testing Zoledronic Acid in people with Chondrosarcoma, run by Mohammed Milhem at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chondrosarcoma
- What is being tested?
- Zoledronic Acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jul 2017to 1 May 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 20Show fewer
- Platelet count of > 100,000/mm3
- Hemoglobin \≥ 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
- Serum albumin >/= 3g/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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
About this study
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.
Read the 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 (for years 1 and 2) with local and systemic imaging.
Expansion Cohort:
The phase 1 b 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 (for years 1 and 2).
- Conditions
- Chondrosarcoma
- Being tested
- Zoledronic Acid
- Medical subject headings
- Chondrosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic AcidDrug
Also called Zometa®
Zoledronic acid, a member of bisphosphonate class, inhibits bone resorption.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Zoledronic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.)
Measured: 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.
Measured: 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
Recurrence-free survival will be estimated using the Kaplan-Meier method.
Measured: All eligible patients that have initiated treatment will be considered evaluable for assessing recurrence free survival for up to 2 years.
Overall survival
Overall survival will be estimated using the Kaplan-Meier method.
Measured: All eligible patients that have initiated treatment will be considered evaluable for assessing overall survival up to 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2017
- Study start18 Jul 2017
- Primary completion20 Apr 2023
- Study completion1 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ChondrosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model 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.
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mohammed Milhem
- Sponsor type
- University, hospital or other
- Collaborators
- Rising Tide Foundation
- Responsible party
- Sponsor-investigator, Mohammed Milhem, University of Iowa
- Investigators
- Mohammed Milhem, MBBS, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03173976
- Sponsor's protocol ID
- 201610743
- Status last verified
- Nov 2025
- First submitted
- 29 May 2017
- Last updated
- 6 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-Osteoclast Therapy as Neoadjuvant in Treatment of Chondrosarcoma - Phase 1b Trial
- ClinicalTrials.gov ID
- NCT03173976
- Acronym / sponsor ID
- 201610743
- Conditions
- Chondrosarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Mohammed MilhemUniversity, hospital or other
- Collaborators
- Rising Tide Foundation
- Study start
- 18 Jul 2017 (actual)
- Primary completion
- 20 Apr 2023 (actual)
- Study completion
- 1 May 2028 (estimated)
- First posted
- 2 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 (for years 1 and 2) with local and systemic imaging.
Expansion Cohort:
The phase 1 b 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 (for years 1 and 2).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model 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.
| Arm | Type | Receives |
|---|---|---|
| Zoledronic Acid | Experimental | Drug: Zoledronic Acid1 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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:
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zoledronic AcidAlso: Zometa®Zoledronic acid, a member of bisphosphonate class, inhibits bone resorption. | Drug | Zoledronic Acid |
Primary outcome
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.)
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.
2 secondary outcomes
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.
Overall survival
Time frame: All eligible patients that have initiated treatment will be considered evaluable for assessing overall survival up to 5 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohammed Milhem, MBBS principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zoledronic Acid in people with Chondrosarcoma, run by Mohammed Milhem at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2025.