GALLANT: Metronomic Gemcitabine, Doxorubicin, Docetaxel and Nivolumab for Advanced Sarcoma

Sarcoma Clinical Trial

Official title:

GALLANT: A Phase 2 Study Using Metronomic Gemcitabine, Doxorubicin, Docetaxel and Nivolumab as Second/Third Line Therapy for Advanced Sarcoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04535713
• Other study ID #: SOC-2082
• Status: Recruiting
• Phase: Phase 2
• Start date: September 30, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2023
• Source: Sarcoma Oncology Research Center, LLC
• Contact: Sant P Chawla, MD
• Phone: 3105529999
• Email: santchawla[@]sarcomaoncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open label phase 2 study for advanced sarcoma using metronomic doses of gemcitabine, doxorubicin and docetaxel, and nivolumab immunotherapy given intravenously.

Description:

This is an open label phase 2 study for advanced sarcoma using metronomic doses of gemcitabine, doxorubicin and docetaxel, and nivolumab immunotherapy given intravenously. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: December 31, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically confirmed diagnosis of locally advanced, unresectable or metastatic sarcoma
• Ability to understand the purposes and risks of the study and has signed and dated a written informed consent form approved by the Investigator's IRB/Ethics Committee
• Willingness to comply with all study procedures and availability for the duration of the study.
• Previously treated patient with measurable disease by RECIST v1.1
• ECOG performance status = 2
• Life expectancy of at least 3 months
• Acceptable cardiac function with LV ejection fraction of > 50%
• Acceptable liver function: Bilirubin < 1.5 times upper limit of normal (ULN; except subjects with Gilbert Syndrome who must have a total bilirubin level < 3.0 ULN); AST (SGOT), ALT (SGPT) and alk phos < 2.5 x ULN (< 5 x ULN if liver metastases present)
• Acceptable renal function: Creatinine < 1.5 times ULN and creatinine clearance > 60 ml/min using the Crockroft-Gault formula
• Acceptable hematologic status: ANC >1000 cells/µL; Platelet count >100,000/µL; Hemoglobin > 9.0 g/dL
• INR and PT < 1.5 ULN unless taking anti-coagulation, in which case PT, INR and aPTT must be within therapeutic range of intended use of anticoagulants
• All women of childbearing potential must have a negative urine or serum pregnancy test within 72 hours of enrollment. If urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; all subjects must agree to use highly effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 5 months for women and 7 months for men after the last dose.

Exclusion Criteria:

• History or evidence of active autoimmune disease that requires systemic treatment (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Currently receiving treatment with another investigational device or drug study, or <14 days since ending treatment with another investigational device or drug study(s).
• Subject has known sensitivity to gemcitabine, doxorubicin, docetaxel or nivolumab.
• Female subject is pregnant or breast-feeding or planning to become pregnant during study treatment and through 3 months after the last dose of gemcitabine, doxorubicin, docetaxel or nivolumab.
• Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of gemcitabine, doxorubicin, docetaxel or nivolumab.
• Sexually active subjects and their partners unwilling to use male or female latex condom

Related Conditions & MeSH terms

• Sarcoma

Intervention

Drug:
• Gemcitabine
600 mg/m2 (Maximum Dose: 1000 mg) i.v. on Day 1 and Day 8 of Cycle 1+
• Doxorubicin
18 mg/m2 (Maximum Dose: 32 mg) i.v. on Day 1 and Day 8 of Cycle 1+
• Docetaxel
25 mg/m2 (Maximum Dose: 42 mg) i.v. on Day 1 and Day 8 of Cycle 1+
• Nivolumab
240 mg i.v. on Day 1 beginnning Cycle 2+

Locations

Country	Name	City	State
United States	Sant P Chawla	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Sarcoma Oncology Research Center, LLC

Country where clinical trial is conducted

United States, 

References & Publications (5)

Chawla SP, Sankhala KK, Ravicz J, Kang G, Liu S, Stumpf N, Leong B, Kim S, Arasheben S, Tseng WW, Gordon EM. Clinical experience with combination chemo-/immunotherapy using trabectedin and nivolumab for advanced soft tissue sarcoma. J Clin Oncol 36, 2018

Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, et al. Efficacy and Safety of TRABECTEDIN or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Mul

Gordon EM, Sankhala KK, Chawla N, Chawla SP. Trabectedin for Soft Tissue Sarcoma: Current Status and Future Perspectives. Adv Ther. 2016 Jul;33(7):1055-71. doi: 10.1007/s12325-016-0344-3. Epub 2016 May 27. — View Citation

Tawbi, HA, Burgess MA, Crowley J et al. Safety and efficacy of PD-1 blockade using pembrolizumab in patients with advanced soft tissue (STS) and bone sarcomas (BS): Results of SARC028-A multicenter phase II study. J Clin Oncol 34, 2016 (suppl; abstr 11006

www.accessdata.fda.gov/drugsatfda_docs (Gemcitabine, Doxorubicin, Docetaxel, Nivolumab)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	Progression free survival from start of treatment to disease progression or death from any cause	12 months
Secondary	Overall response	Overall response by RECIST v1.1 via CT scan or MRI during the treatment period	6 weeks
Secondary	Adverse Events	Incidence of treatment related adverse events	12 months