Gemcitabine + Docetaxel + Radiation for Soft Tissue Sarcoma

Overseen By Ashley Fansler, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Wake Forest University Health Sciences

Must not be taking: Hormonal therapy, Biologic, Chemotherapy

Disqualifiers: Pregnancy, Nursing, Amputation, others

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

Compensation: Varies

Number of Visits: Unknown

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two chemotherapy drugs, gemcitabine and docetaxel, along with radiation therapy, to determine its safety and effectiveness for treating soft tissue sarcoma, a cancer affecting connective tissues. The goal is to assess the treatment's effectiveness before surgery to remove the tumor. It suits adults with a confirmed Grade II or III soft tissue sarcoma that is operable and who have not received radiation on the affected limb. This study aims to determine if this treatment combination can improve outcomes for individuals with this cancer type. 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 treatment combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking any concurrent hormonal therapy, biologic, or other chemotherapy, except for women on hormonal contraceptives. If you are taking an investigational agent, you will also need to stop.

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

Research shows that combining the drugs gemcitabine and docetaxel with radiation can be administered safely with few side effects. In previous studies, patients tolerated this treatment well without needing hospitalization, allowing for outpatient care.

For individuals with soft tissue sarcoma, this combination has been used to help shrink tumors. Although the treatment includes chemotherapy drugs (gemcitabine and docetaxel) and radiation, earlier research found that the side effects were not severe.

Overall, while some risks exist, past evidence suggests this treatment is generally safe for patients. However, since this is an early trial, the researchers are closely monitoring safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Gemcitabine, Docetaxel, and radiation therapy for soft tissue sarcoma because it offers a unique approach compared to standard treatments like surgery, radiation alone, or traditional chemotherapy regimens. This treatment is distinctive because it integrates both chemotherapy and radiation in a neoadjuvant setting, potentially enhancing the cancer-killing effects before surgery. The use of a 3+3 dose escalation plan allows for personalized treatment, optimizing the dosage for maximum effectiveness while minimizing side effects. This innovative approach could lead to better outcomes and improved quality of life for patients with soft tissue sarcoma.

What evidence suggests that this combination treatment could be effective for soft tissue sarcoma?

This trial will evaluate the combination of gemcitabine and docetaxel with radiation for treating soft tissue sarcoma. Research has shown that this combination might help treat soft tissue sarcoma and can be administered safely with only mild side effects. In past cases, patients with advanced sarcomas responded well to this treatment, indicating its potential effectiveness. This combination has also been used successfully for similar conditions, suggesting it could work for this type of cancer. Overall, while more research is needed, early results suggest this treatment may help shrink tumors in soft tissue sarcoma. ^{1 2 5 6 7}

Who Is on the Research Team?

Shailaja Raj, MRCP

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

Adults over 18 with Grade II or III soft tissue sarcoma that can be surgically removed and are eligible for pre-op radiation. They must have an ECOG performance status of 2 or less, agree to use contraception, and not be pregnant. Excluded are those on other cancer treatments, prior unplanned surgery on the limb, needing amputation, or with specific sarcoma subtypes.

Inclusion Criteria

I agree to use effective birth control or abstain from sex during the study.

Ability to understand and the willingness to sign a written informed consent document

My sarcoma is Grade II or III, can be surgically removed, and I am eligible for radiation before surgery.

Exclusion Criteria

My sarcoma type has standard chemotherapy treatments available.

I need an amputation for my condition.

I am not on any cancer treatments except if I'm using hormonal contraceptives.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy Plus Radiation Therapy

Participants receive up to 6 cycles of chemotherapy with a 3+3 dose escalating plan along with radiation for up to 6 weeks

6 weeks

Weekly chemotherapy and daily radiation visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Post-surgery monitoring

Long-term Follow-up

Long term follow-up will occur every 3-4 months for 24 months in person or video consultation

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Gemcitabine
• Radiation

Trial Overview The trial is testing the safety and effectiveness of combining gemcitabine and docetaxel drugs with radiation therapy before surgical removal of the tumor in adults with soft tissue sarcoma of the limbs.

How Is the Trial Designed?

Group I: Neoadjuvant Chemotherapy Plus Radiation Therapy Experimental Treatment 5 Interventions

Up to 6 cycles (once a week) of chemotherapy with a 3+3 dose escalating plan (from 100 mg to 300 mg for Gemcitabine; 10 mg to 25 mg for Docetaxel) along with radiation (five days a week) for up to 6 weeks.

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?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a review of 21 patients with synovial sarcoma treated with gemcitabine/docetaxel chemotherapy, the treatment showed a low response rate of only 5% and a median progression-free survival of just 2 months, indicating limited efficacy.

Despite the expected toxicities associated with this chemotherapy combination, treatment was tolerated without discontinuation due to toxicity, but the authors recommend that this regimen should not be used outside of clinical trials for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poor treatment outcomes with palliative gemcitabine and docetaxel chemotherapy in advanced and metastatic synovial sarcoma. Pender, A., Davis, EJ., Chauhan, D., et al.[2022]

Gemcitabine-based regimens, particularly gemcitabine alone and gemcitabine-docetaxel, show activity in treating pretreated uterine and non-uterine leiomyosarcoma, but the overall evidence for gemcitabine's effectiveness in sarcomas is limited due to conflicting results from non-randomized trials.

The GeDDIS phase III trial suggests that gemcitabine-docetaxel may be less effective and more toxic than doxorubicin in treating chemo-naïve metastatic soft tissue sarcoma, highlighting the need for further controlled studies to better assess its role in sarcoma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine-based chemotherapy in sarcomas: A systematic review of published trials. Ducoulombier, A., Cousin, S., Kotecki, N., et al.[2022]

In a study of 10 pediatric patients with relapsed or refractory sarcomas, the combination of gemcitabine and docetaxel showed significant antitumor activity, with 50% of patients achieving a complete or partial response.

The treatment was well-tolerated, with only mild toxicities reported, and allowed for a median duration of response of 10 months, indicating a good quality of life for the patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel. Mora, J., Cruz, CO., Parareda, A., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3322200/

Weekly Gemcitabine and Docetaxel in Refractory Soft ... The reported response rate (RR) from five phase II trials of single-agent gemcitabine treatment in patients with soft tissue and bone sarcoma was 3-18% (median ...

2. ascopubs.org ascopubs.org/doi/10.1200/jco.2009.27.15_suppl.e21503

Efficacy and safety of administration of gemcitabine ... Conclusions: Gemcitabine and taxotere combination with radiation therapy can be administered safely on outpatient basis with minimal toxicity. Further safety ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5784639/

Gemcitabine and Docetaxel Combination for Advanced Soft ... This nationwide retrospective study was conducted to evaluate the efficacy and safety of combined gemcitabine and docetaxel (GD) as an off-label therapy for ...

4. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045%2817%2930622-8/fulltext

Gemcitabine and docetaxel versus doxorubicin as first-line ... This study compared gemcitabine and docetaxel versus doxorubicin as first-line treatment for advanced or metastatic soft-tissue sarcoma. Methods.

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5923-7

Gemcitabine and docetaxel combination chemotherapy for ... This study will evaluate the efficacy and safety of combination therapy with gemcitabine and docetaxel for bone sarcomas and STS.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-04227

Gemcitabine and Docetaxel with Radiation Therapy before ... Giving gemcitabine, docetaxel, and radiation therapy to patients with soft tissue sarcoma of the extremities may lead to a reduction in the size of the tumor ...

7. eviq.org.au eviq.org.au/medical-oncology/sarcoma/soft-tissue-sarcoma/1898-soft-tissue-sarcoma-metastatic-docetaxel-and

Soft tissue sarcoma metastatic DOCEtaxel and gemcitabine Median overall survival was 16+ months (range:.4-41.3 months). CONCLUSION: Fixed-dose rate gemcitabine plus docetaxel achieves high objective response rates as ...