Chemotherapy + Immunotherapy for Advanced Sarcoma

Overseen By Sant P Chawla, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sarcoma Oncology Research Center, LLC

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Active autoimmune disease, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: up to 12 months

260 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy and immunotherapy for individuals with advanced sarcoma. The researchers aim to determine how effectively the drugs work together to slow or stop the cancer. The treatment involves administering four drugs—gemcitabine, doxorubicin, docetaxel, and nivolumab (an immunotherapy drug)—through an IV. This trial may suit those diagnosed with advanced sarcoma that cannot be surgically removed and who have already received some form of treatment. Participants should be able to handle the study procedures and commit to its entire duration. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on an investigational drug or device, you must have stopped it at least 14 days before joining this study.

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

Research shows that the treatments in this trial have varying safety levels. Docetaxel can cause serious side effects, such as allergic reactions and fluid buildup, so patients sensitive to certain substances should exercise caution. Doxorubicin may lead to heart problems, occurring during treatment or even years later, with common side effects including tiredness and nausea. Gemcitabine, when combined with other drugs, generally proves effective for some cancers. Studies indicate that using it with docetaxel in sarcoma cases yields better results than using doxorubicin alone. Nivolumab, an immunotherapy drug, can cause the immune system to attack healthy cells, resulting in various side effects, some of which can be serious.

These treatments have been studied in different cancers, providing some insight into their safety. However, as this trial is in an earlier phase, more specific safety information for this combination in advanced sarcoma is still being gathered. Participants should consult their healthcare providers about potential side effects and benefits to better understand the risks. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for sarcoma?

Researchers are excited about this treatment for advanced sarcoma because it combines traditional chemotherapy with immunotherapy, aiming to enhance the body's immune response against cancer. While standard treatments often involve just chemotherapy, this approach adds nivolumab, an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combination could potentially improve outcomes by not only directly targeting cancer cells with chemotherapy but also by boosting the immune system's ability to fight the disease.

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

Research has shown that combining the drugs nivolumab, gemcitabine, doxorubicin, and docetaxel may help treat advanced sarcoma. In this trial, all participants will receive this combination therapy. Studies suggest that these drugs work better together than individually, creating a stronger effect. This combination might also cause fewer severe side effects compared to traditional chemotherapy. Gemcitabine and docetaxel have already shown some effectiveness against advanced sarcoma, and adding nivolumab could enhance their impact. Early results are promising, indicating this treatment could benefit people with advanced sarcoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Sant P Chawla, MD

Principal Investigator

Sarcoma Oncology Research Center, LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced sarcoma that's inoperable or has spread, who understand the study and agree to follow its procedures. They must have had prior treatment, be reasonably healthy (ECOG ≤ 2), not on certain blood thinners, and have good organ function. Women of childbearing age need a negative pregnancy test and must use effective contraception.

Inclusion Criteria

My sarcoma cannot be surgically removed and has spread.

My blood clotting tests are normal or managed if I'm on blood thinners.

Acceptable hematologic status: ANC >1000 cells/μL; Platelet count >100,000/μL; Hemoglobin > 9.0 g/dL

Exclusion Criteria

I am not willing to use birth control during and for 3 months after treatment.

I am on medication for an autoimmune disease, not including hormone replacement.

I am sexually active and unwilling to use a latex condom.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metronomic doses of gemcitabine, doxorubicin, docetaxel, and nivolumab intravenously every 3 weeks

up to 12 months

Visits on Day 1 and Day 8 of each 3-week cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Doxorubicin
• Gemcitabine
• Nivolumab

Trial Overview The GALLANT trial tests low-dose chemotherapy drugs Gemcitabine, Doxorubicin, Docetaxel combined with Nivolumab immunotherapy in patients with advanced sarcoma. It's an open-label phase 2 study where all participants receive the same treatment intravenously.

How Is the Trial Designed?

Group I: Single arm Experimental Treatment 4 Interventions

A total of 260 patients will receive gemcitabine 600 mg/m2 (maximum dose: 1000 mg) on D1 and D8, doxorubicin 18 mg/m2 on D1 and D8 (maximum dose: 32 mg), docetaxel 25 mg/m2 on D1 and D8 (maximum dose: 42 mg), on Days 1 and 8. After the first cycle, nivolumab 240 mg IV will be added on Day 1 of each cycle (see product information; www.accessdata.fda.gov). Treatment cycles are given every 3 weeks. Patients in this study may continue treatment until significant disease progression or unacceptable toxicity occurs up to one year of therapy. Patients who withdraw or do not complete the first 2 treatment cycles and first follow up CT scan/MRI will be replaced.

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?

Sarcoma Oncology Research Center, LLC

Lead Sponsor

Trials

9

Recruited

910+

Published Research Related to This Trial

Doxorubicin (ADR) and ifosfamide have shown single-agent response rates above 20% in advanced soft tissue sarcoma, but the overall role of chemotherapy in these cases remains controversial.

Combination therapies like ADR + DTIC and CYVADIC have higher response rates, yet most studies indicate no significant survival benefit from chemotherapy compared to control groups, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for soft tissue sarcoma--current concepts and review]. Umeda, T., Ishii, T., Hatakeyama, K., et al.[2013]

The combination of pembrolizumab and doxorubicin in treating advanced soft-tissue sarcoma (STS) showed manageable toxicity, with the study meeting its primary safety endpoint and a notable incidence of hematologic adverse events, particularly neutropenia.

The treatment demonstrated promising efficacy, with an overall response rate of 36.7% and disease control in 80% of patients, alongside a median progression-free survival of 5.7 months and overall survival of 17 months, indicating potential benefits for patients with anthracycline-naive advanced STS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Pembrolizumab in Combination with Doxorubicin in Metastatic and Unresectable Soft-Tissue Sarcoma. Livingston, MB., Jagosky, MH., Robinson, MM., et al.[2022]

In a phase II study involving 29 patients with advanced soft tissue sarcomas, docetaxel (Taxotere) showed a partial response rate of 17%, indicating some efficacy as a second-line chemotherapy option.

The treatment was associated with significant side effects, including severe leucopenia in 76% of patients and various neurotoxicities, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study with docetaxel (Taxotere) in advanced soft tissue sarcomas of the adult. EORTC Soft Tissue and Bone Sarcoma Group. van Hoesel, QG., Verweij, J., Catimel, G., et al.[2020]

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]

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 involving 257 patients with advanced soft-tissue sarcoma, the effectiveness of gemcitabine and docetaxel was found to be similar to doxorubicin, with no significant difference in the proportion of patients alive and progression-free at 24 weeks (46.3% vs 46.4%).

Doxorubicin remains the standard first-line treatment for most patients, as the trial showed no treatment-related deaths and similar safety profiles, although both treatments had common adverse effects like neutropenia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Seddon, B., Strauss, SJ., Whelan, J., et al.[2022]

A Phase Ib/II trial showed that combining the monoclonal antibody olaratumab with doxorubicin significantly improved median overall survival for patients with unresectable/metastatic soft tissue sarcoma compared to doxorubicin alone.

Olaratumab has been approved for use with doxorubicin in adult patients who have not previously received anthracycline treatment, marking a promising advancement in treatment options for this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaratumab for the treatment of soft-tissue sarcoma. Pender, A., Jones, RL.[2018]

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]

The combination of cyclophosphamide, adriamycin, imidazole carboxamide (DTIC), and actinomycin D (CAIA) has been used in treating advanced soft tissue sarcomas, showing response rates between 24-60%.

Adding methanol extraction residue of BCG (MER) to the CAIA regimen may enhance the treatment's effectiveness, potentially improving outcomes for patients with advanced sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preliminary study of cyclophosphamide (NSC-26271), adriamycin (NSC-123127), imidazole carboxamide (NSC-45388), and actinomycin D (NSC-3053) with or without MER-BCG in patients with advanced sarcomas. Creagan, ET., Edmonson, JH., Hahn, RG., et al.[2019]

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]

In a study of 80 patients with high-risk soft tissue sarcoma, the gemcitabine and docetaxel (GD) regimen showed a trend towards lower hospitalization rates and better disease-free survival (DFS) compared to the standard doxorubicin and ifosfamide (AI) regimen, although the differences were not statistically significant.

The GD regimen was generally better tolerated, with fewer severe hematologic toxicities compared to AI, suggesting that GD could be a promising alternative for patients with localized, resectable high-grade soft tissue sarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, open-label, phase II study of neo/adjuvant doxorubicin and ifosfamide versus gemcitabine and docetaxel in patients with localised, high-risk, soft tissue sarcoma. Davis, EJ., Chugh, R., Zhao, L., et al.[2022]

In a study involving 340 patients with metastatic sarcomas, adding ifosfamide to the doxorubicin and dacarbazine regimen significantly increased the response rate from 17% to 32%, indicating a more effective treatment option.

While the addition of ifosfamide resulted in more myelosuppression and a longer time to progression (6 months vs. 4 months), the overall survival advantage was not significant, suggesting that while ifosfamide improves response rates, it may also increase toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. Antman, K., Crowley, J., Balcerzak, SP., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e23569

Update on GALLANT: A phase 2 study using metronomic ... The data suggests that nivolumab plus metronomic doses of gemcitabine, doxorubicin and docetaxel (1) may have synergistic activity, and (2) by indirect ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5524246/

Treatment of advanced, metastatic soft tissue sarcoma Given its modest efficacy as second-line therapy, our practice is to use the combination of gemcitabine, 900 mg/m2 on days 1 and 8, and docetaxel 100 mg/m2 on ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT403750

Results of SOC-2082 phase 2 study using metronomic ... Background: Metronomic dosing of gemcitabine, doxorubicin and docetaxel causes less severe side effects than standard chemotherapy for advanced sarcoma.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04535713

Study Details | NCT04535713 | GALLANT: Metronomic ... This is an open label phase 2 study for advanced sarcoma using metronomic doses of gemcitabine, doxorubicin and docetaxel, and nivolumab immunotherapy given ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5622179/

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.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2013/020449s071lbl.pdf

Taxotere (docetaxel) Label - accessdata.fda.gov WARNING: TOXIC DEATHS, HEPATOTOXICITY, NEUTROPENIA,. HYPERSENSITIVITY REACTIONS, and FLUID RETENTION. See full prescribing information for complete boxed ...

7. products.sanofi.us products.sanofi.us/taxotere/taxotere.html

TAXOTERE® (docetaxel) injection, for intravenous use Severe hypersensitivity reactions have been reported in patients despite dexamethasone premedication. Hypersensitivity reactions require immediate ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK537242/

Docetaxel - StatPearls - NCBI Bookshelf - NIH Hypersensitivity reactions: Avoid docetaxel in patients with severe hypersensitivity to docetaxel or other polysorbate 80-formulated drugs.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/215813s000lbl.pdf

DOCETAXEL injection, for intravenous use - accessdata.fda.gov Docetaxel 75 mg/m2: Treatment-emergent adverse drug reactions are shown in Table 7. Included in this table are safety data for a total of 176 patients with non- ...

10. aetna.com aetna.com/cpb/medical/data/900_999/0956.html

Docetaxel - Medical Clinical Policy Bulletins Docetaxel at a dose of 100 mg/m2 , however, was associated with unacceptable hematologic toxicity, infections, and treatment-related mortality and this dose ...