BLESSED: Expanded Access for DeltaRex-G for Advanced Pancreatic Cancer, Sarcoma and Carcinoma of Breast

Pancreatic Cancer Clinical Trial

Official title:

BLESSED: Expanded Access for DeltaRex-G for Advanced Pancreatic Cancer, Sarcoma and Carcinoma of Breast

Clinical Trial Details — Status: Available

Administrative data

• NCT number: NCT04091295
• Other study ID #: AF19-200
• Status: Available

Study information

• Verified date: May 2024
• Source: Aveni Foundation
• Contact: ERLINDA M GORDON, MD
• Phone: 3105529999
• Email: egordon[@]sarcomaoncology.com
• Is FDA regulated: No
• Study type: Expanded Access

Clinical Trial Summary

Forty patients with pancreatic cancer, sarcoma and carcinoma of breast will receive DeltaRex-G intravenously at a dose of 1-4 x 10e11 colony forming units (cfu) or equivalent 0.6-1.8 x 10e10 RV copies per dose one to three times a week. DeltaRex-G may be given alone or with one or more FDA approved cancer therapies/immunotherapies.

Based on previous Phase 1/2 US based clinical studies, DeltaRex-G does not suppress the bone marrow or cause serious organ dysfunction, and enhanced immune cell trafficking in tumors may cause the tumors to appear larger or new lesions to appear on CT, PET or MRI. Further, tumor stabilization/regression/remission may occur later during the treatment period. Therefore, DeltaRex-G will be continued regardless of CT, PET or MRI results if the patient has clinical benefit and does not have symptomatic disease progression.

Description:

DeltaRex-G is a targeted tumor agnostic gene therapy that displays a Sig-binding peptide for binding to abnormal collagenous Signature (Sig) proteins in the tumor microenvironment and encoding a CCNG1 inhibitor gene for killing cancer cells, its blood supply and stroma producing fibroblasts, thus reducing extracellular matrix production and augmented drug entry and immune cell trafficking in tumors. Enhanced CCNG1 expression has been found in all cancer types tested at the Cancer Center of Southern California as of June 2023. Hence, in July 2023, the USFDA authorized the use of DeltaRex-G as platform therapy upon which one or more FDA approved cancer drugs/immunotherapies may be added. This would allow a personalized approach in the treatment of all cancer patients.

Forty patients with pancreatic cancer, sarcoma and carcinoma of breast will receive DeltaRex-G intravenously at a dose of 1-4 x 10e11 colony forming units (cfu) or equivalent 0.6-1.8 x 10e10 RV copies per dose one-three times a week. DeltaRex-G may be given alone or with an FDA approved cancer therapy/immunotherapy on physician discretion.

Based on previous Phase 1/2 US based clinical studies, DeltaRex-G does not suppress the bone marrow or cause serious organ dysfunction, and enhanced immune cell trafficking in tumors may cause the tumors to appear larger or new lesions to appear on CT, PET or MRI. Further, tumor stabilization/regression/remission may occur later during the treatment period. Therefore, DeltaRex-G will be continued regardless of CT, PET or MRI results if the patient has clinical benefit and does not have symptomatic disease progression.

If the patient develops a treatment-related >Grade 3 adverse event, the DeltaRex-G infusions will be held and the patient will be monitored until the toxicity has resolved to

Recruitment information / eligibility

• Status: Available
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 100 Years

Eligibility

Inclusion Criteria:

• Patient is =12 years of age, either male or female for patients with sarcoma; >18 years of age, either male or female for pancreatic cancer and carcinoma of breast.

• Patient has advanced metastatic pancreatic cancer or advanced metastatic sarcoma confirmed by pathologic examination at diagnosis.

• Patients with advanced metastatic pancreatic cancer who have received systemic therapies such as FOLFIRINOX and gemcitabine + albumin-bound paclitaxel; patients with metastatic sarcoma who have disease progression after two or more lines of systemic treatments and not amenable to surgical resection or radiotherapy; specifically for osteosarcoma: have disease progression after high dose methotrexate, cisplatinum, doxorubicin and ifosfamide; for soft tissue sarcoma: have disease progression after doxorubicin + ifosfamide/mesna, gemcitabine, docetaxel, dacarbazine, trabectedin, pazopanib, eribulin; patients with metastatic carcinoma of breast who have disease progression with standard therapy (ACT), targeted therapies including aromatase inhibitors, trastuzumab, pertuzumab, enhertu, tyrosine kinase inhibitors, immune checkpoint inhibitors; patient who is intolerant to or declines available therapeutic options after documentation that patient has been informed of the available therapeutic options.

• Patient is able to understand or is willing to sign a written informed consent.

• Patient agrees to use barrier contraception during vector infusion period and for 6 weeks after infusion

Exclusion Criteria:

• Patient is unwilling to provide formal informed consent.

• Patient is unwilling to use barrier contraception during vector infusion period and for 6 weeks after infusion

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Carcinoma of Breast
• Chondrosarcoma
• Chordoma
• MPNST (Malignant Peripheral Nerve Sheath Tumor)
• Nerve Sheath Neoplasms
• Osteosarcoma
• Pancreatic Cancer
• Pancreatic Neoplasms
• Sarcoma
• Soft Tissue Sarcoma

Intervention

Drug:
• DeltaRex-G
Intravenous infusions of DeltaRex-G for treatment of advanced pancreatic cancer and sarcoma that have failed standard therapies

Locations

Country	Name	City	State
United States	Sarcoma Oncology Research Center, LLC	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Aveni Foundation

Country where clinical trial is conducted

United States, 

References & Publications (8)

Al-Shihabi A, Chawla SP, Hall FL, Gordon EM. Exploiting Oncogenic Drivers along the CCNG1 Pathway for Cancer Therapy and Gene Therapy. Mol Ther Oncolytics. 2018 Dec 12;11:122-126. doi: 10.1016/j.omto.2018.11.002. eCollection 2018 Dec 21. No abstract available. — View Citation

Bruckner HW, Chawla SP, Omelchenko N, Brigham DA, Gordon EM. Phase I-II study using DeltaRex-G, a tumor-targeted retrovector encoding a cyclin G1 inhibitor for metastatic carcinoma of breast. Front. Mol. Med. 3:1105680. doi: 10.3389/fmmed.2023.1105680

Chawla SP, Bruckner H, Morse MA, Assudani N, Hall FL, Gordon EM. A Phase I-II Study Using Rexin-G Tumor-Targeted Retrovector Encoding a Dominant-Negative Cyclin G1 Inhibitor for Advanced Pancreatic Cancer. Mol Ther Oncolytics. 2018 Dec 14;12:56-67. doi: 10.1016/j.omto.2018.12.005. eCollection 2019 Mar 29. — View Citation

Chawla SP, Chawla NS, Quon D, Chua-Alcala V, Blackwelder WC, Hall FL and Gordon EM: An advanced phase 1/2 study using an XC-targeted gene therapy vector for chemotherapy resistant sarcoma. Sarcoma Res Int 3: 1024, 2016

Chawla SP, Chua VS, Fernandez L, Quon D, Saralou A, Blackwelder WC, Hall FL, Gordon EM. Phase I/II and phase II studies of targeted gene delivery in vivo: intravenous Rexin-G for chemotherapy-resistant sarcoma and osteosarcoma. Mol Ther. 2009 Sep;17(9):1651-7. doi: 10.1038/mt.2009.126. Epub 2009 Jun 16. — View Citation

Chawla SP, Olevsky O, Iyengar G, Brigham DA, Omelchenko N, Thomas S, Suryamohan K, Foshag L, Hall FL, Gordon EM. Early-stage CCNG1+ HR+ HER2+ Invasive Breast Carcinoma in Older Women: Current Treatment and Future Perspectives for DeltaRex-G, a CCNG1 Inhibitor. Anticancer Res. 2023 Jun;43(6):2383-2391. doi: 10.21873/anticanres.16406. — View Citation

Gordon EM, Hall FL. Rexin-G, a targeted genetic medicine for cancer. Expert Opin Biol Ther. 2010 May;10(5):819-32. doi: 10.1517/14712598.2010.481666. — View Citation

Kim S, Federman N, Gordon EM, Hall FL, Chawla SP. Rexin-G(R), a tumor-targeted retrovector for malignant peripheral nerve sheath tumor: A case report. Mol Clin Oncol. 2017 Jun;6(6):861-865. doi: 10.3892/mco.2017.1231. Epub 2017 Apr 28. — View Citation