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Recurrent OsteosarcomaPhase 1/2NCT03598595

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

A Phase 1/2 study testing Docetaxel, Gemcitabine and Hydroxychloroquine in people with Recurrent Osteosarcoma and Refractory Osteosarcoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Docetaxel, Gemcitabine and Hydroxychloroquine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
28 Jan 2019to 31 May 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • Toxicities from prior anti-tumor therapy not resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade 0 or 1, or to levels dictated in the eligibility criteria. Grade 2 toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present and stable for > 4 weeks), such as stable grade 2 peripheral neuropathy or ifosfamide-related proteinuria, may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by the principal investigator
  • 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
  • Any co-morbid medical disorder that may increase the risk of toxicity, in the opinion of the investigator
  • All herbal supplements, vitamins, and nutritional supplements taken within the last 30 days prior to dosing on day 1 (and continued use, if appropriate), must be reviewed and approved by the principal investigator (PI)
  • Patients with pre-existing maculopathy or retinopathy of the eye

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Medical subject headings
Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DocetaxelDrug

    Also called Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

    Given IV

  • GemcitabineDrug

    Also called dFdC, dFdCyd, Difluorodeoxycytidine

    Given IV

  • HydroxychloroquineDrug

    Given PO

Study groups in NCT03598595
Study groupRoleWhat they receive
Treatment (hydroxychloroquine, gemcitabine, docetaxel)ExperimentalParticipants 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.
Receives: Drug: Docetaxel; Drug: Gemcitabine; Drug: Hydroxychloroquine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose of hydroxychloroquine (Phase I)

    Measured: Up to 21 days

  2. Disease control rate (Phase II)

    Measured: At 4 months

Secondary outcomes (2)

  1. Event free survival

    Measured: From enrollment to disease progression, death, or discontinuation of treatment for any reason, assessed up to 2 years

  2. Overall response (complete response [CR] or partial response [PR] versus not CR or PR)

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2018
  2. Study start28 Jan 2019
  3. Primary completion31 May 2027 (estimated)
  4. Study completion31 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03598595
Sponsor's protocol ID
2018-0224
Other IDs
NCI-2018-01414, 2018-0224
Status last verified
May 2026
First submitted
16 Jul 2018
Last updated
14 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 31401903

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Docetaxel, Gemcitabine and Hydroxychloroquine in people with Recurrent Osteosarcoma and Refractory Osteosarcoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose of hydroxychloroquine (Phase I) (time frame: Up to 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03598595, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.

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