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

NCT04535713 | Recruiting Phase 2 FDA Drug

• 1 other identifier: SOC-2082
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sarcoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival from start of treatment to disease progression or death from any cause

  12 months

Secondary Outcomes (2)

• Overall response

  6 weeks

• Adverse Events

  12 months

Study Arms (1)

Single arm

EXPERIMENTAL

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.

Drug: Gemcitabine; Drug: Doxorubicin; Drug: Docetaxel; Drug: Nivolumab

Interventions

Gemcitabine DRUG

600 mg/m2 (Maximum Dose: 1000 mg) i.v. on Day 1 and Day 8 of Cycle 1+

Also known as: Gemzar

Single arm

Doxorubicin DRUG

18 mg/m2 (Maximum Dose: 32 mg) i.v. on Day 1 and Day 8 of Cycle 1+

Also known as: Adriamycin

Single arm

Docetaxel DRUG

25 mg/m2 (Maximum Dose: 42 mg) i.v. on Day 1 and Day 8 of Cycle 1+

Also known as: Taxotere

Single arm

Nivolumab DRUG

240 mg i.v. on Day 1 beginnning Cycle 2+

Also known as: Opdivo

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sarcoma Oncology Research Center, LLC: lead

Study Sites (1)

Sant P Chawla

Santa Monica, California, 90403, United States

RECRUITING

Related Publications (5)

• 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.

  PMID: 27234989 RESULT

• 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 Multicenter Clinical Trial. J Clin Oncol. 2015 Sep 14. pii: JCO.2015.62.4734. [Epub ahead of print]. D'Incalci M, Galmarini CM. A Review of TRABECTEDIN (ET-743): A Unique Mechanism of Action. Mol Cancer Ther. 2010; 9:2157-2163.

  RESULT

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

  RESULT

• 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 (suppl; abstr e23568)

  RESULT

• 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)

  RESULT

MeSH Terms

Conditions

Sarcoma

Interventions

Gemcitabine; Doxorubicin; Docetaxel; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sant P Chawla, MD

  Sarcoma Oncology Research Center, LLC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sant P Chawla, MD

CONTACT

3105529999; santchawla@sarcomaoncology.com

Victoria Chua-Alcala

CONTACT

3105529999; vchua@sarcomaoncology.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 27, 2020
• First Posted: September 2, 2020
• Study Start: September 30, 2020
• Primary Completion: September 30, 2025
• Study Completion: December 31, 2025
• Last Updated: July 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)