Ignite Creation Date:
2025-12-24 @ 1:49 PM
Ignite Modification Date:
2026-01-01 @ 7:23 AM
Study NCT ID:
NCT03598595
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-12
First Post:
2018-07-16
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Gemcitabine, Docetaxel, and Hydroxychloroquine in Treating Participants With Recurrent or Refractory Osteosarcoma
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
A Phase 1/2 Study of Gemcitabine and Docetaxel in Combination With Hydroxychloroquine (Autophagy Inhibitor) in Patients With Recurrent Osteosarcoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: