NK Cells + Chemotherapy for Sarcoma

(TINKS Trial)

Recruiting at 23 trial locations

Overseen By Jessica Crimella, BSN, RN, CCRP

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nationwide Children's Hospital

Must not be taking: Corticosteroids, Diazepam, CYP3A4 inducers

Disqualifiers: CNS metastases, HIV, others

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

Compensation: Varies

Number of Visits: 1

Duration: 24 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding "natural killer" (NK) cells to standard chemotherapy can improve treatment outcomes for childhood sarcomas that have recurred or resisted previous treatments. The trial aims to assess the safety and effectiveness of this combination and whether it helps patients remain cancer-free for at least six months. Participants will receive cycles of chemotherapy, including drugs like Docetaxel and Gemcitabine, along with NK cells. This study suits those with relapsed or hard-to-treat osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, or other soft tissue sarcomas who have already tried several treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but you cannot take other cancer treatments or certain medications like strong CYP3A4 inducers and diazepam. It's best to discuss your specific medications with the study team.

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

Research has shown that using gemcitabine and docetaxel together is generally safe, with manageable side effects. One study found that this combination can be safely administered to outpatients, with only mild side effects. However, like many chemotherapy treatments, side effects such as low blood counts, nausea, and tiredness can occur.

The use of TGFβi expanded NK cells remains under investigation. These NK cells aim to help the body's immune system fight cancer, but more information is needed to confirm their safety. As this is an early stage of testing, the safety of this treatment is still being determined. Early trials are designed to closely monitor for any negative reactions.

Docetaxel has already received FDA approval for treating other types of cancer, indicating its safety in those cases. This trial tests the safety of using these treatments together in a new way. Participants will be closely monitored for any side effects or issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of NK cells with chemotherapy for treating sarcomas because it offers a unique approach compared to traditional treatments. Most current therapies, like surgery, radiation, and chemotherapy, aim to remove or shrink tumors. However, this new treatment introduces natural killer (NK) cells, which are a type of immune cell that can target and destroy cancer cells more precisely. By combining NK cells with the chemotherapy agents Docetaxel and Gemcitabine, the treatment not only attacks the cancer through traditional means but also boosts the body's immune response, potentially leading to a more effective and comprehensive treatment option for difficult-to-treat sarcomas like osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma.

What evidence suggests that NK cells + chemotherapy might be an effective treatment for sarcoma?

Research has shown that using gemcitabine and docetaxel together can help treat sarcomas, with studies finding that about 42% of patients experienced some tumor shrinkage with this combination. In this trial, participants will receive either the gemcitabine and docetaxel combination or a treatment involving a type of immune cell called NK cells. Early results suggest that a special kind of NK cells, called TGFβi expanded NK cells, could enhance the immune system's ability to fight cancer. This is promising because NK cells can find and destroy cancer cells more effectively. Although more research is needed, these treatments together could improve outcomes for sarcomas that have returned or are difficult to treat. ^{6 7 8 9 10}

Who Is on the Research Team?

Bhuvana Setty, M.D.

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for young people aged 12-40 with relapsed or refractory pediatric bone and soft tissue sarcomas, who've had limited prior treatments. They must have a certain level of physical ability, adequate organ function, controlled seizures if present, no severe allergies to specific drugs used in the study, and agree to use contraception.

Inclusion Criteria

Contraception: Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Men must also agree to use adequate contraception

Patients must have measurable disease using RECIST 1.1 criteria

I have had 1-4 treatments for sarcoma and surgery or radiation if needed.

Exclusion Criteria

Patients who may not be able to comply with the safety monitoring requirements of the study

My tumor is close to vital body parts where swelling could cause major issues.

My cancer is only in my bone marrow.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 8 cycles of gemcitabine, docetaxel, and TGFβi NK cells, each cycle lasting 21 days

24 weeks

Visits on Days 1, 8, 9, and 12 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Gemcitabine
• TGFβi expanded NK cells

Trial Overview The study tests whether adding TGFβ imprinted NK cells (a type of immune cell) to standard chemotherapy (gemcitabine and docetaxel) improves outcomes for these sarcoma patients. The treatment involves multiple cycles of chemo plus NK cell infusions over several weeks.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Part 1: Enrollment of 5 patients in each cohort (osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and non-rhabdomyosarcoma). Part 2: Enrollment of 2 cohorts in 2 stages for a total of 40 patients.

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?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

National Pediatric Cancer Foundation

Collaborator

Trials

8

Recruited

300+

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]

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 ANNOUNCE 2 trial investigated the addition of olaratumab to the standard treatment of gemcitabine and docetaxel for advanced soft tissue sarcomas, involving 256 patients across two cohorts (O-naïve and O-pretreated).

The study found no statistically significant improvement in overall survival between the treatment groups, indicating that adding olaratumab did not enhance the effectiveness of the existing regimen, while safety profiles remained manageable with no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas. Attia, S., Villalobos, V., Hindi, N., et al.[2023]

Docetaxel, a chemotherapy drug for castration-resistant prostate cancer (CRPC), can impair the effectiveness of natural killer (NK) cells by increasing the expression of the inhibitory ligand LLT1 through androgen receptor (AR) signaling, which may contribute to docetaxel resistance.

Targeting the androgen receptor or blocking LLT1 can potentially enhance NK cell activity against CRPC cells, suggesting new therapeutic strategies to overcome docetaxel resistance in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel suppresses immunotherapy efficacy of natural killer cells toward castration-resistant prostate cancer cells via altering androgen receptor-lectin-like transcript 1 signals. Tang, M., Gao, S., Zhang, L., et al.[2020]

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]

This study is the first prospective trial assessing the combination of gemcitabine and docetaxel in patients with advanced synovial sarcoma, achieving a 3-month progression-free rate of 45.4%, indicating potential efficacy in this challenging cancer.

Despite early closure due to slow patient enrollment, the treatment showed manageable toxicity with 31.8% of patients experiencing grade 3 or worse side effects, and quality of life measures remained stable, suggesting that further research is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of gemcitabine and docetaxel combination in relapsed metastatic or unresectable locally advanced synovial sarcoma. Tansir, G., Rastogi, S., Kumar, A., et al.[2023]

In a study of 11 patients with sarcoma, nanosomal docetaxel lipid suspension (NDLS) chemotherapy showed promising efficacy, with a 50% overall response rate and a 66.7% disease control rate in metastatic cases, indicating its potential effectiveness in treating this type of cancer.

NDLS-based chemotherapy was well tolerated, with no new safety concerns identified, although 63.6% of patients experienced at least one adverse event, primarily hematological and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Sarcoma: A Multicenter, Retrospective Study. Narayanan, P., Dattatreya, PS., Prasanna, R., et al.[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 study involving 37 patients with advanced soft tissue sarcoma resistant to prior treatments, docetaxel showed very limited efficacy, with only 2.8% of patients experiencing a partial remission.

The study found that the median progression-free survival was 42 days and overall survival was 350 days, indicating that docetaxel does not provide significant benefits for patients with this type of cancer who have already been treated with anthracyclines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of Activity of Docetaxel in Soft Tissue Sarcomas: Results of a Phase II Study of the Italian Group on Rare Tumors. Santoro, A., Romanini, A., Rosso, A., et al.[2021]

Citations

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Phase II study with Docetaxel (Taxotere®) in advanced soft ... Current regimens for treatment of distant metastases of soft tissue sarcomas result in response rates of about 25%. Therefore the search for active drugs ...

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Docetaxel - StatPearls - NCBI Bookshelf - NIH Docetaxel, in combination with cisplatin, is approved by the Federal Drug Agency (FDA) as a first-line treatment for prostate cancer.

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statistical review and evaluation - accessdata.fda.gov Study 2 (ARD6006) was a Phase 2 single-arm study to determine the response rate and safety of. Taxotere monotherapy in patients with relapsed/refractory Ewing ...

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Systemic Therapy Outcomes in Adult Patients with Ewing ... The median overall survival for the entire group was 20.65 months (range 0.43–114.54). In patients with localized disease, the 1-, 2-, and 3-year survival rates ...

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A Post-Marketing Surveillance Study to Evaluate the Safety ... Tannock et al demonstrated that patients with prostate cancer who used docetaxel and prednisone had a better outcome than patients taking mitoxantrone and ...