A Phase I Clinical Trial of Neoadjuvant Chemotherapy With/Without SPIONs/SMF for Patients With Osteosarcoma

Phase 1

• Conditions: Osteosarcoma
• Interventions: Drug: neoadjuvant chemotherapy+SPIONs/SMF; Drug: neoadjuvant chemotherapy

• Registration Number: NCT04316091
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

Osteosarcoma is the most common primary malignant bone tumor that mainly occurs in children and adolescents. Combined surgical resection and intensive chemotherapy has improved the 5-year overall survival rate (from 51 to 75%). However, drug-induced side effects and tumor recurrence after surgery reduce patient quality of life and cut down the patient survival rate. Superparamagnetic Iron Oxide Nanoparticles (SPIONs)/Spinning Magnetic Field (SMF) and neoadjuvant chemotherapy may increase the cancer cell killing and complete tumor shrinkage preserving local structures and functions of patients who cannot receive limb retention treatment.

Detailed Description

This study aims to evaluate the safety, efficacy, and tolerability of SPIONs/SMF in combination with neoadjuvant chemotherapy in osteosarcoma patients. They will receive intratumoral injection of SPIONs every other day for 3 times, followed by SMF for 2 hours every two days, and up to completion of 30 days, and conventional neoadjuvant chemotherapy from day 1. The sponsor hypothesizes that SPIONs/SMF will act synergistically with neoadjuvant chemotherapy to increase the cancer cell killing, to increase the local efficacy of neoadjuvant chemotherapy, and to improve the ratio of limb retention. Then, all patients will be followed every 8 weeks, for the safety evaluation and cancer disease status until the end of the study.

Study Timeline

• Status Verified: 2020-03
• Study First Submitted: 2020-03-16
• Study First Submitted QC: 2020-03-19
• Last Update Submitted: 2020-03-19
• Study First Posted: 2020-03-20
• Last Update Posted: 2020-03-20
• Study Start: 2020-09-01
• Primary Completion: 2021-08-31
• Study Completion: 2023-08-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Signed informed consent form
• Biopsy-confirmed cancer diagnosis
• Has at least one tumor lesion that can be accurately measured according to RECIST 1.1. and is amenable for intratumoral injection
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy >12 weeks
• Karnofsky performance status (KPS) ≥ 70
• Adequate function of organs and bone marrow
• Negative pregnancy test ≤ 7 days prior to SPIONs injection

Exclusion Criteria

• Symptomatic central nervous system metastases and/or carcinomatous meningitis
• Known HIV or active hepatitis B/C infection
• Active infection requiring systemic treatment
• Received a live virus vaccine within 30 days prior to study treatment
• History of pneumonitis that required steroids or with current pneumonitis
• Has received prior systemic anti-neoplastic therapy, within 4 weeks prior to SPIONs injection
• Clinically significant cardiac arrhythmias
• Class III or IV Congestive Heart Failure as defined by the New York Heart Association functional classification system < 6 months prior to screening
• A pregnant or nursing female, or women of child-bearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
• Any condition for which participation would not be in the best interest of the participant
• Patients unable to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures or those with severe psychiatric illness/social situations that would limit compliance with study requirements
• Patients participating in another clinical investigation at the time of signature of the informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental group	neoadjuvant chemotherapy+SPIONs/SMF	neoadjuvant chemotherapy+SPIONs/SMF
Control group	neoadjuvant chemotherapy	neoadjuvant chemotherapy

Primary Outcome Measures

Name	Time	Method
Determination of the Recommended Dose	36 Months	Determination of dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) (if possible), and recommended Phase 2 doses (RP2Ds)

Secondary Outcome Measures

Name	Time	Method
Evaluation of the anti-tumor response of neoadjuvant chemotherapy±SPIONs/SMF	36 Months	Evaluation of the Objective Response Rate: complete or partial response, as defined by RECIST 1.1
Evaluation of the body kinetic profile of intratumorally injected neoadjuvant chemotherapy±SPIONs/SMF	36 Months	Evaluation of the time-course dependent accumulation (μg/dL) of iron in blood and urine following SPIONs intratumoral injection
Assessment of the safety and feasibility of neoadjuvant chemotherapy±SPIONs/SMF	36 Months	Assessment of the number of participants with related late onset toxicities defined as any Grade ≥3 adverse event (AE) occurring after the end of treatment (EOT) visit