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 uses a combination of chemotherapy and immunotherapy to treat patients with advanced sarcoma. The chemotherapy attacks the cancer directly, while the immunotherapy boosts the body's natural defenses to help fight the cancer.

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 the combination of chemotherapy and immunotherapy safe for treating advanced sarcoma?

The combination of gemcitabine and docetaxel has been studied in advanced sarcoma and is generally considered manageable in terms of safety, with no new safety concerns observed. However, it may be more toxic than some other treatments like doxorubicin in certain cases. ^{1 2 3 4 5}

What makes the chemotherapy and immunotherapy drug combination unique for advanced sarcoma?

This treatment combines chemotherapy drugs (Docetaxel, Doxorubicin, Gemcitabine) with an immunotherapy drug (Nivolumab), which is a novel approach for advanced sarcoma. While chemotherapy drugs attack cancer cells directly, Nivolumab helps the immune system recognize and fight cancer cells, potentially offering a more comprehensive treatment strategy. ^{1 6 7 8 9}

What data supports the effectiveness of the drug combination of chemotherapy and immunotherapy for advanced sarcoma?

Research shows that combining doxorubicin with other treatments like olaratumab has improved survival in some sarcoma patients. Additionally, gemcitabine and docetaxel have been effective in treating advanced soft tissue sarcomas, although the prognosis remains challenging. ^{1 6 10 11 12}

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

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]

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]

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]

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]

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]

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 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 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]

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]

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 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]

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]

Citations

1. United States 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas. [2023]

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

Olaratumab for the treatment of soft-tissue sarcoma. [2018]

4. England 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. [2022]

5. England 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. [2020]

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

Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel. [2022]

7. Egypt pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Sarcoma: A Multicenter, Retrospective Study. [2022]

8. England 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. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Gemcitabine-based chemotherapy in sarcomas: A systematic review of published trials. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

[Chemotherapy for soft tissue sarcoma--current concepts and review]. [2013]

11. United States 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. [2019]

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

Phase II Study of Pembrolizumab in Combination with Doxorubicin in Metastatic and Unresectable Soft-Tissue Sarcoma. [2022]