A Two-part Phase IIb Trial of Vigil in Ewing's Sarcoma

• Status: Completed
• Trial end date: 2021-01-31
• Target enrollment: 0
• Participant gender: All

Summary

Based on the limited accrual to Part 1 of this study, Gradalis is opening Part 2 of this clinical protocol to assess the safety of Vigil immunotherapy in combination with irinotecan and temozolimidetemozolomide. Part 2 will be conducted at the same centers as Part 1, studying intradermal autologous Vigil cancer vaccine (1.0 x 10e7 cells/injection; minimum of 4 to a maximum of 12 administrations) in patients with metastatic Ewing's sarcoma Family of Tumors (ESFT) refractory or intolerant to at least 1 prior line of chemotherapy. Patients undergoing a standard surgical procedure (e.g., tumor biopsy or palliative resection) may have tumor tissue harvested for manufacture of investigational product. Patients meeting eligibility criteria including manufacture of a minimum of 4 immunotherapy doses of Vigil will be registered to receive: (i) oral temozolimidetemozolomide 100 mg/m2 daily (Days 1 - 5, total dose 500 mg/m2/cycle), (ii) irinotecan 50 mg/m2 daily (Days 1 - 5, total dose 250mg/m2/cycle), orally or irinotecan 20mg/m2 daily (Days 1 - 5, total dose 100mg/m2/cycle), intravenously (iii) peg-filgrastim 100μg/kg (Day 6) subcutaneously (optional and may be administered at home), and (iv) Vigil 1.0 x 10e7 cells/injection, intradermally on Day 15 and every 3 weeks thereafter. One cycle = 21 days.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gradalis, Inc.
• Treatments: Armodafinil; Docetaxel; Gemcitabine; Irinotecan; Modafinil; Temozolomide

Criteria

Tissue Procurement Inclusion Criteria:

Patients will be eligible for tissue procurement for the Vigil manufacturing process, if they meet all of the following criteria:

1. Histologically confirmed Ewing's Sarcoma Family of Tumors (ESFT).

2. Age ≥2 years.

3. Estimated survival ≥ 6 months.

4. Evidence of EWS translocation by FISH or RT-PCR or Next Generation Sequencing (NGS).

5. Metastatic disease

6. Refractory or intolerant to at least 1 line of systemic chemotherapy.

7. Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative mass of ~10-30 grams tissue ("golf-ball" size) or pleural fluid estimated volume ≥ 500mL (must be primary tap) for immunotherapy manufacture.

8. Tumor intended for immunotherapy manufacture is not embedded in bone and does not contain luminal tissue (e.g. bowel, ureter, bile duct).

9. Ability to understand and the willingness to sign a written informed consent document for tissue harvest.

Tissue Procurement Exclusion Criteria:

Patients meeting any of the following criteria are not eligible for tissue procurement for the Vigil manufacturing:

1. Medical condition requiring any form of chronic systemic immunosuppressive therapy (steroid or other) except physiologic replacement doses of hydrocortisone or equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily) for < 30 days duration.

2. Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.

3. Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.

4. Any documented history of autoimmune disease with exception of Type 1 diabetes on stable insulin regimen, hypothyroidism on stable dose of replacement thyroid medication, vitiligo, or asthma not requiring systemic steroids.

5. Known history of allergies or sensitivities to gentamicin.

6. History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.

7. Known HIV or chronic Hepatitis B or C infection.

Study Enrollment Inclusion Criteria:

Patients will be eligible for registration if they meet all of the following inclusion criteria:

1. Successful manufacturing of at least 4 vials of Vigil.

2. Karnofsky performance status (PS) ≥80%.

3. Estimated survival ≥ 6 months.

4. Normal organ and marrow function as defined below:

Absolute granulocyte count ≥1,500/mm3 Absolute lymphocyte count ≥400/mm3 Platelets ≥100,000/mm3 Total bilirubin ≤ institutional upper limit of normal AST(SGOT)/ALT(SGPT) ≤2x institutional upper limit of normal Creatinine <1.5 mg/dL

5. Subject has recovered to CTCAE Grade 1 or better from all adverse events associated with prior therapy or surgery. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade 2 or better.

6. If female of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry.

7. Ability to understand and the willingness to sign a written informed protocol specific consent.

Study Enrollment Exclusion Criteria:

Measureable disease is not a requirement for enrollment onto the trial.

In addition to the procurement exclusion criteria, patients will NOT be eligible for study registration and randomization if meeting any of the following criteria:

1. Any anti-neoplastic therapy between tissue procurement for Vigil manufacture and start of study therapy.

2. Live vaccine used for the prevention of infectious disease administered < 30 days prior to the start of study therapy.

3. Post-surgery complication that in the opinion of the treating investigator would interfere with the patient's study participation or make it not in the best interest of the patient to participate.