Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Sarcoma Oncology Research Center, LLC
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
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.
Is the drug combination of Docetaxel, Doxorubicin, Gemcitabine, and Nivolumab promising for advanced sarcoma?The combination of these drugs shows potential because Gemcitabine and Docetaxel are effective for advanced sarcoma, and Doxorubicin is a standard treatment. Adding Nivolumab, an immunotherapy drug, could enhance the effectiveness of chemotherapy, making this combination promising for treating advanced sarcoma.1381112
What safety data exists for chemotherapy and immunotherapy in advanced sarcoma treatment?The safety data for chemotherapy regimens involving gemcitabine and docetaxel in advanced sarcoma treatment indicate that these treatments are generally manageable. The ANNOUNCE 2 trial found no new safety signals when adding olaratumab to gemcitabine and docetaxel, and safety was manageable across treatment arms. A study comparing doxorubicin and ifosfamide with gemcitabine and docetaxel suggested that gemcitabine and docetaxel may be better tolerated. However, gemcitabine-docetaxel was found to be more toxic than doxorubicin in chemo-naïve metastatic soft tissue sarcoma patients according to the GeDDIS phase III trial. Overall, the level of evidence supporting the use of gemcitabine-based regimens in sarcoma management is limited, and confirmatory phase III trials are needed.5671012
What data supports the idea that Chemotherapy + Immunotherapy for Advanced Sarcoma is an effective treatment?The available research shows mixed results for the effectiveness of Chemotherapy + Immunotherapy for Advanced Sarcoma. One study found that adding the drug olaratumab to doxorubicin improved survival for patients with soft tissue sarcoma. However, another study combining olaratumab with gemcitabine and docetaxel did not show a significant improvement in survival. Overall, while some combinations show promise, the effectiveness of Chemotherapy + Immunotherapy for Advanced Sarcoma varies, and more research is needed to confirm its benefits.248912
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop your current medications. However, if you are on systemic treatment for an active autoimmune disease, you may not be eligible. It's best to discuss your specific medications with the trial team.
Eligibility Criteria
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.
I can take care of myself but might not be able to do heavy physical work.
My cancer can be measured by standard imaging tests.
I am not pregnant and agree to use effective birth control during and after the study.
My heart pumps blood well, with an ejection fraction over 50%.
My kidney function is within the required range.
Exclusion Criteria
I am on medication for an autoimmune disease, not including hormone replacement.
I am sexually active and unwilling to use a latex condom.
I am allergic to gemcitabine, doxorubicin, docetaxel, or nivolumab.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Single armExperimental Treatment4 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Sant P ChawlaSanta Monica, CA
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Who is running the clinical trial?
Sarcoma Oncology Research Center, LLCLead Sponsor
References
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]Polychemotherapy for soft tissue sarcomas has been reported to produce response rates ranging from 24--60% (1, 2). Immunotherapy has reportedly prolonged survival after surgery for some tumors and enhanced the effectiveness of chemotherapy (3, 4). This report summarizes our preliminary experience with the combination of cyclophosphamide, adriamycin, imidazole carboxamide (DTIC), and actinomycin D (CAIA) with or without methanol extraction residue of BCG (MER) in patients with advanced sarcomas.
Phase II study with docetaxel (Taxotere) in advanced soft tissue sarcomas of the adult. EORTC Soft Tissue and Bone Sarcoma Group. [2020]Current regimens for treatment of distant metastases of soft tissues sarcomas result in response rates of about 25%. Therefore the search for active drugs remains a task for investigational groups. Taxoids offer a new class of cytostatic drugs. Docetaxel has been studied as a second line chemotherapy in advanced soft tissue sarcomas of the adult.
[Chemotherapy for soft tissue sarcoma--current concepts and review]. [2013]The role of chemotherapy for soft tissue sarcoma with the exception of rhabdomyosarcoma remains controversial. Several randomized trials have suggested only doxorubicin (ADR) and ifosfamide produced a single-agent response rate above 20% in advanced sarcoma. As a combination chemotherapy, the doxorubicin-based combination, ADR + DTIC (ADIC) and CYVADIC, showed a higher response rate. Ifosfamide in addition to doxorubicin (Ifos + ADR or ADIC) appeared to have major activity with a higher complication rate. The role and value of adjuvant chemotherapy have not yet been established. Most randomized studies have suggested that no survival benefit was observed in the chemotherapy group relative to the control group. Further basic and clinical investigation is necessary to obtain a better prognosis in high-grade malignant soft tissue sarcoma.
An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. [2022]Doxorubicin alone or with dacarbazine (DTIC; AD) is considered the best available therapy for metastatic adult sarcomas. Ifosfamide is active in sarcomas that have failed to respond to a doxorubicin-based regimen. This study was designed to determine if ifosfamide added to doxorubicin and DTIC (ADI) significantly effects toxicity, response rate, and survival. Patients with measurable metastatic or unresectable sarcoma were randomized to receive AD or ADI. Patients with chondrosarcomas, fibrosarcomas, and other sarcomas of bone were eligible, although those with osteosarcoma, rhabdomyosarcoma, Ewing's sarcoma, Kaposi's sarcoma, and mesothelioma were excluded, as were patients with prior chemotherapy for sarcoma or prior doxorubicin.
Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel. [2022]In this report we describe experience with gemcitabine-docetaxel in pediatric patients with relapsed or refractory sarcomas.
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]Doxorubicin and ifosfamide (AI) is standard therapy for high-risk soft tissue sarcoma (STS) but often causes severe toxicities resulting in hospitalisation. Gemcitabine and docetaxel (GD) has efficacy in metastatic STS and may be better tolerated. We conducted a study to compare toxicities and efficacies of these regimens.
Gemcitabine-based chemotherapy in sarcomas: A systematic review of published trials. [2022]Gemcitabine is largely used in the management of sarcomas. We have systematically reviewed all of the fully published trials that investigated a gemcitabine-based regimen in the management of sarcomas and then provided a grade of recommendations and a level of evidence for every recommendation. Because of conflicting results from successive non-randomized phase II trials, gemcitabine activity alone in unselected pretreated soft tissue sarcomas could not be properly assessed. Gemcitabine alone and gemcitabine-docetaxel appeared to both be active in pretreated uterine and non-uterine leiomyosarcoma (1B;I). Gemcitabine-dacarbazine appeared to be active in pretreated unselected soft tissue sarcomas (1B;I). According the GeDDIS phase III trial (not yet fully published), gemcitabine-docetaxel appeared slightly less active than doxorubicine and more toxic than doxorubicine in chemo-naïve metastatic soft tissue sarcoma patients. Because of the absence of controlled randomized trials, the benefit of gemcitabine-docetaxel as an adjuvant treatment in high-grade uterine leiomyosarcoma could not be appropriately assessed. The level of activity of gemcitabine/docetaxel in bone sarcomas cannot be ascertained with the available data. The level of evidence supporting the use of gemcitabine-based regimens in sarcoma management is limited. Confirmatory phase III trials are warranted when phase II trials suggest some preliminary activity.
Olaratumab for the treatment of soft-tissue sarcoma. [2018]The outcome for patients with unresectable/metastatic soft tissue sarcoma remains poor with few treatment options. In the first line setting, a number of randomized trials have shown no difference in overall survival between combination anthracycline schedules and single agent doxorubicin. A Phase Ib/randomized Phase II trial of doxorubicin with or without the monoclonal antibody to PDGFR-α, olaratumab, demonstrated a significant difference in median overall survival in favor of the olaratumab arm. The results of this trial led to approval of olaratumab in combination with doxorubicin in adult anthracycline-naive unresectable soft tissue sarcoma. In this review, we describe some of the preclinical and early clinical data of olaratumab in sarcomas, the Phase Ib/II trial and ongoing trials with olaratumab in sarcomas.
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]For many years, first-line treatment for locally advanced or metastatic soft-tissue sarcoma has been doxorubicin. This study compared gemcitabine and docetaxel versus doxorubicin as first-line treatment for advanced or metastatic soft-tissue sarcoma.
Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Sarcoma: A Multicenter, Retrospective Study. [2022]To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) based chemotherapy in patients with sarcoma.
Phase II Study of Pembrolizumab in Combination with Doxorubicin in Metastatic and Unresectable Soft-Tissue Sarcoma. [2022]Doxorubicin is standard therapy for advanced soft-tissue sarcoma (STS) with minimal improvement in efficacy and increased toxicity with addition of other cytotoxic agents. Pembrolizumab monotherapy has demonstrated modest activity and tolerability in previous advanced STS studies. This study combined pembrolizumab with doxorubicin to assess safety and efficacy in frontline and relapsed settings of advanced STS.
Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas. [2023]Gemcitabine plus docetaxel is an effective treatment regimen for advanced soft tissue sarcomas (STSs). However, the prognosis for patients remains poor, and thus there is an urgent medical need for novel and effective therapies to improve long-term outcomes. The aim of the ANNOUNCE 2 trial was to explore the addition of olaratumab (O) to gemcitabine (G) and docetaxel (D) for advanced STS. Adults with unresectable locally advanced/metastatic STS, ≤2 prior lines of systemic therapy, and ECOG PS 0-1 were eligible. In Phase 2, patients were randomized 1:1 from two cohorts (O-naïve and O-pretreated) to 21-day cycles of olaratumab (20 mg/kg Cycle 1 and 15 mg/kg other cycles, Days 1 and 8), gemcitabine (900 mg/m2, Days 1 and 8), and docetaxel (75 mg/m2, Day 8). The primary objective was overall survival (OS) in the O-naïve population (α level = 0.20). Secondary endpoints included OS (O-pretreated), other efficacy parameters, patient-reported outcomes, safety, pharmacokinetics, and immunogenicity. A total of 167 and 89 patients were enrolled in the O-naïve and O-pretreated cohorts, respectively. Baseline patient characteristics were well balanced. No statistically significant difference in OS was observed between the investigational vs. control arm for either cohort (O-naïve cohort: HR = 0.95 (95% CI: 0.64-1.40), p = 0.78, median OS, 16.8 vs. 18.0 months; O-pretreated cohort: HR = 0.67 (95% CI: 0.39-1.16), p = 0.15, median OS 19.8 vs. 17.3 months). Safety was manageable across treatment arms. There was no statistically significant difference in the primary endpoint of OS between the two arms in the O-naïve population, and therefore based on hierarchical evaluation no other outcomes in this study can be considered statistically significant. No new safety signals were observed.