Triple Drug Therapy for Osteosarcoma

Overseen By John Livingston

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Gemcitabine, Docetaxel

Disqualifiers: Second neoplasm, Cardiac issues, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days per cycle

31 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that any herbal supplements, vitamins, and nutritional supplements must be reviewed and approved by the principal investigator. It's best to discuss your current medications with the trial team to get a clear answer.

What data supports the effectiveness of the triple drug therapy for osteosarcoma?

Research shows that the combination of gemcitabine and docetaxel has been effective in treating recurrent or hard-to-treat osteosarcoma, with better outcomes observed at higher doses of gemcitabine. This suggests that these drugs work well together in fighting this type of bone cancer. ^{1 2 3 4 5}

Is the combination of gemcitabine and docetaxel safe for humans?

The combination of gemcitabine and docetaxel has been used in various cancer treatments, including osteosarcoma and breast cancer. It is generally considered safe, but it can cause side effects like neutropenia (a low level of white blood cells), which can increase the risk of infection. In studies, the rates of severe neutropenia ranged from 29% to 79%, and febrile neutropenia (fever with low white blood cells) ranged from 0% to 18%. ^{1 2 3 6 7}

How is the triple drug therapy for osteosarcoma different from other treatments?

The triple drug therapy for osteosarcoma, involving docetaxel and gemcitabine, is unique because it combines these two drugs to treat patients with recurrent or hard-to-treat forms of the disease, offering a potential new option where few treatments exist. This combination has shown promising results in improving outcomes for patients with advanced or relapsed osteosarcoma, which is a challenging condition to treat. ^{1 2 5 8 9}

Research Team

John A Livingston, MD MS

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for people with osteosarcoma that has returned or isn't responding to treatment. They must have a certain level of kidney function, measurable disease, and be able to perform daily activities with some limitations. Participants need available tumor tissue for research and should not have had previous treatments with the drugs being tested in this study.

Inclusion Criteria

Absolute neutrophil count (ANC) >= 1.0 x 10^9/L

I can care for myself and am up more than 50% of my waking hours.

My liver enzymes are within normal limits for my age.

Exclusion Criteria

I haven't had cancer treatment in the last 21 days, or targeted therapy in the last 28 days.

I do not have acute hepatitis B or C, but if chronic, it is stable and not a safety risk.

I have an eye condition affecting my macula or retina.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hydroxychloroquine orally once or twice daily on days 1-21, gemcitabine intravenously on days 1 and 8, and docetaxel intravenously on day 8. Courses repeat every 21 days.

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

1 year

Treatment Details

Interventions

• Docetaxel
• Gemcitabine
• Hydroxychloroquine

Trial Overview The trial is testing the combination of three chemotherapy drugs: gemcitabine, docetaxel, and hydroxychloroquine. It aims to find the safest doses and see how well they work together against recurrent or stubborn osteosarcoma by stopping cancer cells from growing or spreading.

Participant Groups

Group I: Treatment (hydroxychloroquine, gemcitabine, docetaxel) Experimental Treatment 3 Interventions

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.

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase II trial involving 53 patients with recurrent Ewing sarcoma, osteosarcoma, or chondrosarcoma, the combination of gemcitabine and docetaxel showed low efficacy, with partial responses observed in only a few patients and no complete responses.

The trial indicated a very low probability of achieving the target response rates for osteosarcoma (less than 5%) and Ewing sarcoma (5.6%), leading to the decision to close these arms due to insufficient efficacy and slow patient enrollment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of sequential gemcitabine followed by docetaxel for recurrent Ewing sarcoma, osteosarcoma, or unresectable or locally recurrent chondrosarcoma: results of Sarcoma Alliance for Research Through Collaboration Study 003. Fox, E., Patel, S., Wathen, JK., et al.[2022]

The combination of gemcitabine and docetaxel has shown effectiveness in treating metastatic sarcomas, particularly in leiomyosarcoma and undifferentiated high-grade pleomorphic sarcoma, expanding treatment options for oncologists.

There is evidence suggesting that the combination may work synergistically, especially since docetaxel alone has a low response rate, indicating that using both drugs together could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel in metastatic sarcoma: past, present, and future. Maki, RG.[2022]

In a study of 22 pediatric patients with recurrent or refractory sarcomas, the combination of gemcitabine and docetaxel showed a 29% overall objective response rate, indicating promising antitumor activity, especially in osteosarcoma and malignant fibrous histiocytoma.

The treatment was well tolerated, with manageable side effects primarily including thrombocytopenia and neutropenia, suggesting that this combination could be a viable option for young patients with difficult-to-treat sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of gemcitabine and docetaxel in the treatment of children and young adults with refractory bone sarcoma. Navid, F., Willert, JR., McCarville, MB., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Higher Gemcitabine Dose Was Associated With Better Outcome of Osteosarcoma Patients Receiving Gemcitabine-Docetaxel Chemotherapy. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel for the treatment of children and adolescents with recurrent or refractory osteosarcoma: Korea Cancer Center Hospital experience. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Phase II study of sequential gemcitabine followed by docetaxel for recurrent Ewing sarcoma, osteosarcoma, or unresectable or locally recurrent chondrosarcoma: results of Sarcoma Alliance for Research Through Collaboration Study 003. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel in metastatic sarcoma: past, present, and future. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Combination of gemcitabine and docetaxel in the treatment of children and young adults with refractory bone sarcoma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel in metastatic breast cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gemcitabine-docetaxel combination therapy for recurrent or refractory high-grade osteosarcoma in China: a retrospective study of 18 patients. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel combination chemotherapy for advanced bone and soft tissue sarcomas: protocol for an open-label, non-randomised, Phase 2 study. [2022]