Trial of Bi-shRNA-furin and GMCSF Augmented Autologous Tumor Cell Vaccine for Advanced Cancer

Completed · Phase 1

Conditions studied: Ewings Sarcoma, Non Small Cell Lung Cancer, Liver Cancer

In brief

Autologous Vigil™ vaccine expresses rhGMCSF and bi-shRNAfurin from the Vigil™ plasmid. The GMCSF protein is a potent stimulator of the immune system, recruiting immune effectors to the site of intradermal injection and promoting antigen presentation. The furin bifunctional shRNA blocks furin protein production at the post transcriptional and translational levels. This decrease in furin in turn decreases the conversion of the proforms TGFβ1 and TGFβ2 proteins. Also, reduced furin protein levels have a negative feedback inhibition on TGFβ1 and TGFβ2 gene expression, decreasing the levels of their mRNAs. The resulting decrease in TGFβ1 and TGFβ2 proteins reduces the local immunosuppression they cause and promotes tumor surface antigen and MHC protein display.

Key facts

Study ID: NCT01061840
Run by: Gradalis, Inc.
People needed: 100
Starts: 2009-12-01
Expected to finish: 2019-01-01
Last updated by the study team: 2022-03-15

Who can join

Age: 12 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Histologically confirmed advanced or metastatic non-curable solid tumor (if limited to a single lesion may not be a candidate for curative surgery or radiation therapy). Successful vaccine manufacture has resulted from tissue/fluid obtained from the following major organ systems: digestive, endocrine, reproductive, respiratory, and urinary.Individuals manufactured under CL-PTL 105 (Phase II Ovarian) may be eligible for enrollment without advanced or metastatic disease.
Patients with well differentiated thyroid cancer are eligible for protocol as follows:
Surgically unresectable locally recurrent disease and/or metastatic disease following RAI ablation (if locally recurrent and ultrasound (US) positive, baseline FDG-PET or MRI will be obtained).
Patients with microscopic and/or gross extra thyroidal disease extension without RAI uptake but with a) FDG-PET positive disease or b) suppressed thyroglobulin >1 ng/mL or c) stimulated thyroglobulin >10 ng/L.
Patients with tracheal/esophageal involvement. High mitotic activity or necrosis in pathology does not exclude from the study.
Note: in Categories a and b, patients can be followed using US locally in addition to standard diagnostic followup menu but, if US only is positive, a FDG-PET or MRI will be obtained. If negative, a rising thyroglobulin titer is required in which case response will be monitored by continued US and suppressed and/or stimulated thyroglobulin. Thyroglobulin titer cannot be used if anti-thyroglobulin antibodies are present).
Completed all acceptable therapies with curative intent that are the current standard of care for their respective diseases. If no conventional therapy available, patient may participate after review by sponsor.
Recovered from all clinically relevant toxicities related to prior therapies
Patients will be allowed to participate following single prior CNS treatment with stereotactic radiotherapy whole brain irradiation and stable without steroid requirement for ≥2 months or following ≥2 prior CNS treatments with stereotactic radiotherapy whole brain irradiation and stable without steroid requirement for ≥4 months.
For ESFT patients age ≥12 years.
Age ≥18 years (non-ESFT candidates)
ECOG performance status (PS) 0-1.Pediatric patients with Lansky or Karnofsky Performance Status Scale ≥ of 50%.
Estimated >4 month survival probability.
Normal organ and marrow function as defined below:
Absolute granulocyte count ≥ 1,500/mm3 Absolute lymphocyte count ≥ 500/mm3 Platelets ≥ 100,000/mm3 Total bilirubin ≤2 mg/dL AST(SGOT)/ALT(SGPT) <2x institutional upper limit of normal Creatinine <1.5 mg/dL
Ability to understand and the willingness to sign a written informed consent document. Pediatric patients must sign an assent with a parent or legal guardian sign a written informed consent.
Negative pregnancy test.
Patients must be off all "statin" drugs for ≥2 weeks prior to initiation of therapy.

You may not qualify if…

Surgery involving general anesthesia, radiotherapy, steroid therapy, or immunotherapy within 4 weeks prior to vaccination. Chemotherapy within 3 weeks prior to entering the study. Palliative radiotherapy is allowable. Collection of lumenal tissue for vaccine manufacture must be avoided.
Patients must not have received any other investigational agents within 30 days prior to vaccination.
Concurrent tumor-specific hormonal therapy or antiestrogens. (Individuals manufactured under CL-PTL 105 (Phase II Ovarian) are not subject to this exclusion).
Patients with known active or symptomatic brain metastases prior to vaccination.
Patients with compromised pulmonary disease.
Short term (<30 days) concurrent systemic steroids ≤0.25 mg/kg prednisone per day (maximum 7.5 mg/day) and bronchodilators (inhaled steroids) are permitted; other steroid regimens and/or immunosuppressives are excluded while receiving vaccine. Patients requiring steroids following previous CNS radiation for metastatic disease are excluded.
Prior splenectomy unless Howell-Jolly bodies are absent.
Prior malignancy (excluding nonmelanoma carcinomas of the skin) unless in remission for 2 years.
Kaposi's Sarcoma.
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Patients who are pregnant or nursing.
Patients with known HIV.
Patients with chronic Hepatitis B and C infection. For patients with hepatocellular carcinoma (HCC), the presence of chronic HBV and HCV is NOT an exclusion. Patients must have a viral titer <50 IU/ml x 2 at a minimum of 2 weeks apart.
Patients with uncontrolled autoimmune diseases.

Where it is running

Florida Cancer Specialists — West Palm Beach, Florida, United States
Dartmouth-Hitchcock Medical Center/ Norris Cotton Cancer Center — Lebanon, New Hampshire, United States
Mary Crowley Cancer Research Centers — Dallas, Texas, United States
Cancer Care Northwest — Spokane, Washington, United States

Full record on ClinicalTrials.gov

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