Gemcitabine, Docetaxel, and Hydroxychloroquine in Treating Participants With Recurrent or Refractory Osteosarcoma
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|ClinicalTrials.gov Identifier: NCT03598595|
Recruitment Status : Recruiting
First Posted : July 25, 2018
Last Update Posted : May 9, 2019
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Osteosarcoma Refractory Osteosarcoma||Drug: Docetaxel Drug: Gemcitabine Drug: Hydroxychloroquine||Phase 1 Phase 2|
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)
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.
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2 Study of Gemcitabine and Docetaxel in Combination With Hydroxychloroquine (Autophagy Inhibitor) in Patients With Recurrent Osteosarcoma|
|Actual Study Start Date :||January 28, 2019|
|Estimated Primary Completion Date :||March 2, 2020|
|Estimated Study Completion Date :||March 2, 2020|
Experimental: Treatment (hydroxychloroquine, gemcitabine, docetaxel)
Participants receive hydroxychloroquine PO QD or BID on days 1-21, gemcitabine 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.
- Maximum tolerated dose of hydroxychloroquine (Phase I) [ Time Frame: Up to 21 days ]
- Disease control rate (Phase II) [ Time Frame: At 4 months ]
- Event free survival [ Time Frame: From enrollment to disease progression, death, or discontinuation of treatment for any reason, assessed up to 2 years ]
- Overall response (complete response [CR] or partial response [PR] versus not CR or PR) [ Time Frame: Up to 2 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03598595
|Contact: John Livingstonemail@example.com|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: John A. Livingston 713-792-3626|
|Principal Investigator: John A. Livingston|
|Principal Investigator:||John A Livingston||M.D. Anderson Cancer Center|