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

Brief Title

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

Official Title

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

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.
    

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 Phase

Phase 1

Study Type

Interventional


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

Secondary Outcome

 Recurrence (local or metastatic) free survival

Condition

Chondrosarcoma

Intervention

Zoledronic Acid

Study Arms / Comparison Groups

 Zoledronic Acid
Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

20

Start Date

July 18, 2017

Completion Date

July 1, 2022

Primary Completion Date

July 1, 2022

Eligibility Criteria

        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/mm3; 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; 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 discussion in the multidisciplinary tumor board.

          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 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).
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Varun Monga, MD, 319-384-9497, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03173976

Organization ID

201610743


Responsible Party

Sponsor-Investigator

Study Sponsor

Varun Monga, MD

Collaborators

 Rising Tide Foundation

Study Sponsor

Varun Monga, MD, Principal Investigator, University of Iowa


Verification Date

October 2020