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

NCT03598595 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2018-0224NCI-2018-01414
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Osteosarcoma; Refractory Osteosarcoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of hydroxychloroquine (Phase I)

  Up to 21 days

• Disease control rate (Phase II)

  At 4 months

Secondary Outcomes (2)

• Event free survival

  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)

  Up to 2 years

Study Arms (1)

Treatment (hydroxychloroquine, gemcitabine, docetaxel)

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: Gemcitabine; Drug: Hydroxychloroquine

Interventions

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Treatment (hydroxychloroquine, gemcitabine, docetaxel)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Treatment (hydroxychloroquine, gemcitabine, docetaxel)

Hydroxychloroquine DRUG

Given PO

Treatment (hydroxychloroquine, gemcitabine, docetaxel)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient or patient's legally acceptable representative has provided informed consent
• Patients must have a pathological diagnosis of osteosarcoma at original diagnosis or time of recurrence
• Patients must have relapsed or become refractory to conventional therapy, with a regimen containing some combination of high dose methotrexate, doxorubicin, cisplatin, and/or ifosfamide
• Patients may have either unresectable or potentially resectable disease. However, patients with potentially resectable disease must be willing to await surgery until after the primary efficacy endpoint is reached at 4 months
• Patients must have measurable disease by RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2. Use Karnofsky for patients \> 16 years old and Lansky for patients =\< 16
• Has archived tumor tissue and is willing to provide a tumor block or unstained slides or the patient is willing to undergo a pretreatment biopsy. Biopsy during cycle #2 of therapy is required. Biopsy at progression is strongly encouraged but will be optional
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L
• Platelet count \>= 100 x 10\^9/L
• Hemoglobin \> 8 g/dL
• Prothrombin time (PT) or partial thromboplastin time (PTT) \< 1.5 x upper limit of normal (ULN), except subjects on anticoagulation for venous thromboembolism
• Calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) \> 60 mL/min
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 x ULN for age
• Total bilirubin \< 1.5 x ULN for age
• Serum albumin \>= 2

You may not qualify if:

• Any disorder that compromises the ability of the patient or patient's legally acceptable representative to give written informed consent and/or to comply with the study procedures
• Patients who will not be available for protocol required study visits, to the best of the subject and investigator's knowledge
• History of hypersensitivity to any of the study agents (gemcitabine, docetaxel, or hydroxychloroquine) or to any component of the formulation
• Patients who have previously received gemcitabine or docetaxel
• Men and woman of reproductive potential, unwilling to practice a highly effective method of birth control for the duration of the study and continuing for 2 weeks (for women) and 12 weeks (for men) after receiving the last dose of study drug. Highly effective methods of birth control include sexual abstinence (men, women); vasectomy or a condom used with spermicide (men) in combination with barrier methods, hormonal birth control or intrauterine device (IUD) (women)
• Women who are lactating/breastfeeding or planning to become pregnant during the duration of the study
• History or current diagnosis of a second neoplasm. Exception: adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for \>= 2 years
• Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association \> class II), unstable angina, or unstable cardiac arrhythmia requiring medication, or uncontrolled hypertension (systolic \> 160 mmHg or diastolic \> 100 mmHg)
• Active infection requiring intravenous (IV) antibiotics within 2 weeks of study enrollment
• Significant gastrointestinal disorder(s) that in the opinion of the investigator (e.g., Crohn's disease, ulcerative colitis, extensive gastrointestinal resection) may influence drug absorption
• Known positive test for human immunodeficiency virus (HIV)
• Subjects with acute hepatitis B and C are not eligible. Subjects with chronic hepatitis B or C are eligible if their condition is stable and, in the opinion of the investigator and Amgen physician, if consulted, would not pose a risk to subject safety
• Prior participation in an investigational study and/or procedure within 21 days of study day 1
• Anti-tumor therapy within 21 days of study day 1 including chemotherapy, antibody therapy, or other investigational agent. Enrollment of subjects that have received molecularly targeted agents less than 28 days prior to study day 1 will be permitted if more than 14 days and at least 5 drug half-lives have passed prior to receiving the first dose of HCQ
• Major surgery within 28 days of study day 1

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

  PMID: 31401903 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Osteosarcoma

Interventions

Docetaxel; Gemcitabine; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• John A Livingston

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2018
• First Posted: July 26, 2018
• Study Start: January 28, 2019
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: February 4, 2026

Record last verified: 2026-02

Locations

US (1)