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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of three drugs to treat osteosarcoma, a type of bone cancer that has returned or does not respond to standard treatments. The study aims to determine the best dose of hydroxychloroquine and assess its effectiveness with two chemotherapy drugs, gemcitabine and docetaxel. These drugs work to stop cancer cells from growing or spreading. Individuals with osteosarcoma that did not respond to previous treatments like methotrexate or doxorubicin might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that a combination of three drugs—hydroxychloroquine, gemcitabine, and docetaxel—was tested in patients with advanced bone cancer called osteosarcoma. These studies aimed to determine the optimal dose and identify any side effects. Many patients tolerated the treatment well, though some experienced side effects such as low blood counts, nausea, and tiredness, which are common with chemotherapy drugs like gemcitabine and docetaxel. Hydroxychloroquine, typically used for malaria, was generally well-tolerated but occasionally caused stomach upset or blurred vision. Overall, the treatment appeared promising, with side effects that most participants could manage. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this triple drug therapy for osteosarcoma because it combines hydroxychloroquine, gemcitabine, and docetaxel in a unique way. Unlike standard treatments like methotrexate, doxorubicin, and cisplatin, this regimen includes hydroxychloroquine, which may enhance the effectiveness of chemotherapy by interfering with cancer cell survival mechanisms. Additionally, the combination approach targets cancer cells more aggressively and from multiple angles, potentially leading to improved outcomes. This innovative strategy may offer new hope for patients by overcoming resistance to conventional therapies.

What evidence suggests that this trial's treatments could be effective for osteosarcoma?

Research has shown that combining hydroxychloroquine, gemcitabine, and docetaxel may help treat osteosarcoma, a type of bone cancer. In this trial, participants will receive this combination treatment. Studies have found that gemcitabine and docetaxel together can improve outcomes for patients whose osteosarcoma has returned or is difficult to treat. Researchers are now investigating whether adding hydroxychloroquine can enhance this combination's effectiveness. Hydroxychloroquine might help by preventing cancer cells from surviving under stress. Overall, early results suggest this combination could offer new hope to patients with challenging cases of osteosarcoma. ^{1 2 3 5 6}

Who Is on the Research Team?

John A Livingston, MD MS

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03598595

Study Details | NCT03598595 | Gemcitabine, Docetaxel, ... 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 ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03366-0/fulltext

1756P A phase I/II trial of gemcitabine, docetaxel, and ... We conducted a phase I/II clinical trial of G/D with HCQ to evaluate safety, tolerability, and preliminary efficacy in patients with advanced/metastatic OS.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12274193/

Systemic strategies for osteosarcoma: advances and future ... For example, a study on the combination of ICE showed significant survival benefits in patients with relapsed or refractory bone and soft-tissue ...

4. onclive.com onclive.com/view/dr-livingston-on-the-addition-of-hydroxychloroquine-to-gemcitabine-docetaxel-in-osteosarcoma

Dr Livingston on the Addition of Hydroxychloroquine to ... This study assessed the safety and best dose of hydroxychloroquine and how well it works in combination gemcitabine and docetaxel in the ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11420655/

The efficacy of gemcitabine and docetaxel chemotherapy ... Higher gemcitabine dose was associated with better outcome of osteosarcoma patients receiving gemcitabine‐docetaxel chemotherapy. Pediatr Blood Cancer. 2016 ...

6. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2018-0224.html

A Phase 1/2 Study of Gemcitabine and Docetaxel in ... 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 ...