NCT03598595

Gemcitabine, Docetaxel, and Hydroxychloroquine in Treating Participants With Recurrent or Refractory Osteosarcoma

A Phase 1/2 Study of Gemcitabine and Docetaxel in Combination With Hydroxychloroquine (Autophagy Inhibitor) in Patients With Recurrent Osteosarcoma

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of hydroxychloroquine and how well it works when given together with gemcitabine and docetaxel in treating participants with osteosarcoma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as gemcitabine, docetaxel, and hydroxychloroquine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and preliminary safety of hydroxychloroquine (HCQ) when administered with gemcitabine and docetaxel (G+D) in patients with recurrent/metastatic osteosarcoma. (Phase I) II. To determine whether gemcitabine and docetaxel (G+D) in combination with hydroxychloroquine (HCQ) increases the disease control rate in patients with recurrent/metastatic osteosarcoma at 4 months as compared to historic controls. (Phase II) SECONDARY OBJECTIVES: I. To determine the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) of the combination of G + D + HCQ in patients with recurrent/metastatic osteosarcoma. II. To estimate the event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) for patients with recurrent/metastatic osteosarcoma treated with G+D+HCQ. III. To estimate the toxicity rates of oral HCQ when administered in conjunction with G+D. IV. To investigate the pharmacokinetics (PK) of the combination in patients with recurrent/metastatic osteosarcoma. EXPLORATORY OBJECTIVES: I. To describe the metabolic response rates of G + D + HCQ in patients recurrent/metastatic measurable osteosarcoma by positron emission tomography (PET)/computed tomography (CT) at 6 weeks. II. To assess pre-/post-treatment changes in autophagy biomarkers (autophagic vesicles, LC3B puncta, p62, and HMGB1), HSP27, and pHSP27 expression in tumor samples at baseline and during cycle #2 of treatment with G + D + HCQ. III. To assess the relationship between probability of response and/or disease control and tumor HSP27, pHSP27, ALDH1A1, and HLTF expression. IV. To complete functional proteomic profiling of autophagic and apoptotic pathways on tumor samples by RPPA and correlate findings with the probability response and disease control. OUTLINE: This is a phase I, dose-escalation study of hydroxychloroquine followed by a phase II study. Participants receive hydroxychloroquine orally (PO) once daily (QD) or twice daily (BID) on days 1-21, gemcitabine intravenously (IV) over 90 minutes on days 1 and 8, and docetaxel IV over 1 hours on day 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 1 year.

Conditions

• Recurrent Osteosarcoma
• Refractory Osteosarcoma

Interventions

Type	Name	Description
DRUG	Docetaxel	Given IV
DRUG	Gemcitabine	Given IV
DRUG	Hydroxychloroquine	Given PO

Timeline

• Start date: 2019-01-28
• Primary completion: 2026-05-31
• Completion: 2026-05-31
• First posted: 2018-07-26
• Last updated: 2026-02-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study