A Phase 2 interventional study of Vigil and Temozolomide in Ewing's Sarcoma, sponsored by Gradalis, Inc.. Completed at 6 sites in United States. Open to participants aged 2 Years and older. Per ClinicalTrials.gov, last updated 2022-12-22.
Sponsored by Gradalis, Inc. · Phase 2, Interventional, and Treatment
A two-part trial in patients with metastic Ewing's sarcoma. Participants in Part 1 will be randomized to receive either Vigil immunotherapy or gemcitabine and docetaxel with the objective of comparing the overall survival between the two arms. Participants enrolled in Part 2 will receive Vigil immunotherapy in combination of temozolomide and irinotecan with the objective to determine the safety profile of the combination treatment.
Part 1 Methodology:
This is a multicenter, 1:1 randomized Phase IIb study of intradermal autologous Vigil immunotherapy (1.0 x 10e7 cells/injection; minimum of 4 to a maximum of 12 administrations) versus gemcitabine / docetaxel in patients with metastatic Ewing's sarcoma Family of Tumors (ESFT) refractory or intolerant to at least 2 prior lines 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 will be randomized to receive either (1) intradermal Vigil every 28 days for 4-12 administrations, or (2) gemcitabine 675 mg/m2 IV at 10 mg/m2/min D1 and D8 and docetaxel 75 mg/m2 IV D8 every 21 days. The primary trial objective is to determine the overall survival of patients treated with Vigil versus gemcitabine/docetaxel. Randomization may occur as early as vaccine is released (typically 3 - 4 weeks following tumor procurement) but no later than 8 weeks following tumor procurement. Randomization of patients will be stratified by Karnofsky Performance Status (KPS) ≥ 80% vs \< 80%.
Patients will be managed in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes will be monitored monthly. Blood for immune function analyses including IFNγ-ELISPOT analysis of cytotoxic T cell response to autologous tumor antigens will be collected at tissue procurement, baseline, and prior to product administration at Cycles 2, 4, end of treatment, and every 6 months thereafter.
Part 2 Methodology:
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 temozolomide. 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 temozolomide 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 107 cells/injection, intradermally on Day 15 and every 3 weeks thereafter. One cycle = 21 days. Registration onto Part 2 may occur as early as one week but no later than 8 weeks following tumor procurement. Vigil is typically released approximately 3 weeks after the completion of the two-day manufacturing process.
Patients will be managed in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes will be monitored. Blood for immune function analyses including IFNγ-ELISPOT analysis of cytotoxic T cell response to autologous tumor antigens will be collected at tissue procurement, post-procurement screening and prior to Day 15 Vigil administration at Cycles 2, 4, end of treatment, and every 6 months thereafter. Blood for ctDNA analysis will be collected prior to chemotherapy administration at baseline, Cycle 2 - Week 1 Day 1, Cycle 4 - Week 1 Day 1, and EOT.
1,667 studies on the registry are indexed under Sarcoma; 393 are open to participants now.
This study's enrollment of 22 is below the median of 40 across 1,283 interventional studies indexed under Sarcoma.
Browse Sarcoma studies →Gradalis, Inc. is the lead sponsor of 15 studies on the registry; none are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 4 (80%) have results posted.
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Tissue Procurement Inclusion Criteria:
Patients will be eligible for tissue procurement for the Vigil manufacturing process, if they meet all of the following criteria:
Tissue Procurement Exclusion Criteria:
Patients meeting any of the following criteria are not eligible for tissue procurement for the Vigil manufacturing:
Study Enrollment Inclusion Criteria:
Patients will be eligible for registration if they meet all of the following inclusion criteria:
Normal organ and marrow function as defined below:
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:
Vigil immunotherapy 1.0 x 107 cells/injection; minimum of 4 to a maximum of 12 administrations every 28 days
Biological: Vigil
Gemcitabine 675 mg/m2 IV at 10 mg/m2/min D1 and Docetaxel 75 mg/m2 IV starting on D8 and given every 21 days.
Drug: Gemcitabine · Drug: Docetaxel
(i) oral temozolomide 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 107 cells/injection, intradermally on Day 15 and every 3 weeks thereafter. One cycle = 21 days.
Biological: Vigil · Drug: Temozolomide · Drug: Irinotecan
Vigil 1.0 x 10e7 cells/injection, minimum of 4 to a maximum of 12 administrations.
Also known as: formerly known as FANG™, bi-shRNAfurin and GMCSF Autologous Tumor Cell Immunotherapy
oral temozolimidetemozolomide 100 mg/m2 daily (Days 1 - 5, total dose 500 mg/m2/cycle)
Also known as: TEMODAR
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
Also known as: CAMPTOSAR
675 mg/m2 IV at a rate of 10 mg/m2/min on Day 1 and Day 8 every 21 days
Also known as: GEMZAR
75 mg/m2 IV administered on Day 8 and every 21 days
Also known as: TAXOTERE
Number of Participants With Adverse Events Determined by Laboratory Assessments and Physical Examinations
To determine safety profile of Vigil immunotherapy in combination with irinotecan and temozolomide with 30 days of last dose in patients with metastatic Ewing's sarcoma refractory or intolerant to at least 1 prior line of systemic chemotherapy. • To determine safety profile of Vigil immunotherapy in combination with irinotecan and temozolimidetemozolomide in patients with metastatic Ewing's sarcoma refractory or intolerant to at least 1 prior line of systemic chemotherapy.
Time frame: 30 days of last treatment dosing
Progression Free Survival
Progression Free Survival (PFS) is defined as the time from randomization to the event of disease recurrence/progression defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death due to any cause. To determine the progression free survival of subjects dosed with Vigil immunotherapy in combination with irinotecan and temozolomide.
Time frame: Estimated median 1.3 years
Overall Survival
OS is defined as time from randomization to death or to the date of last follow-up. The date of last follow-up confirming survival will be used as the censoring date for subjects who are alive and/or do not have a known date of death.
Time frame: Estimated median 2 years
| Milestone | Part 1: Vigil Alone | Part 1: Gemicitabine and Docetaxel | Part 2: Vigil in Combination With Temozolomide and Irinotecan |
|---|---|---|---|
| Started | 5 | 8 | 9 |
| Completed | 5 | 7 | 9 |
| Not completed | 0 | 1 | 0 |
To determine safety profile of Vigil immunotherapy in combination with irinotecan and temozolomide with 30 days of last dose in patients with metastatic Ewing's sarcoma refractory or intolerant to at least 1 prior line of systemic chemotherapy. • To determine safety profile of Vigil immunotherapy in combination with irinotecan and temozolimidetemozolomide in patients with metastatic Ewing's sarcoma refractory or intolerant to at least 1 prior line of systemic chemotherapy.
| Participants | Part 1: Vigil Alone | Part 1: Gemcitabine and Docetaxel | Part 2: Vigil in Combination With Temozolomide and Irinotecan |
|---|---|---|---|
| Number of Participants With Adverse Events Determined by Laboratory Assessments and Physical Examinations | 5 | 6 | 9 |
Progression Free Survival (PFS) is defined as the time from randomization to the event of disease recurrence/progression defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death due to any cause. To determine the progression free survival of subjects dosed with Vigil immunotherapy in combination with irinotecan and temozolomide.
| Participants | Part 1: Vigil Alone | Part 1: Gemicitabine and Docetaxel | Part 2: Vigil in Combination With Temozolomide and Irinotecan |
|---|---|---|---|
| Progression Free Survival | 5 | 6 | 9 |
OS is defined as time from randomization to death or to the date of last follow-up. The date of last follow-up confirming survival will be used as the censoring date for subjects who are alive and/or do not have a known date of death.
| Participants | Part 1: Vigil Alone | Part 1: Gemcitabine and Docetaxel | Part 2: Vigil in Combination With Temozolomide and Irinotecan |
|---|---|---|---|
| Overall Survival | 3 | 6 | 5 |
Collected over Adverse events were recorded for the duration of a patient's study treatment: from the first dose of the Investigational Product to 30 days following the last study treatment (up to 10 months).. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1: Vigil Alone | 4/4 (100%) | 2/5 (40%) | 2/5 (40%) |
| Part 1: Gemicitabine and Docetaxel | 8/8 (100%) | 5/8 (62.5%) | 5/8 (62.5%) |
| Part 2: Vigil Plus Temozolomide and Irinotecan | 9/9 (100%) | 5/9 (55.6%) | 9/9 (100%) |
| Event | Part 1: Vigil Alone | Part 1: Gemicitabine and Docetaxel | Part 2: Vigil Plus Temozolomide and Irinotecan |
|---|---|---|---|
| VomitingGastrointestinal disorders | 0/5 | 0/8 | 2/9 |
| Edema extremitiesGeneral disorders | 1/5 | 0/8 | 0/9 |
| Disease progressionGeneral disorders | 1/5 | 0/8 | 1/9 |
| Back painMusculoskeletal and connective tissue disorders | 1/5 | 0/8 | 1/9 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 1/5 | 0/8 | 0/9 |
| Brain massNervous system disorders | 0/5 | 1/8 | 0/9 |
| BlistersSkin and subcutaneous tissue disorders | 0/5 | 1/8 | 0/9 |
| Facial swellingSkin and subcutaneous tissue disorders | 0/5 | 1/8 | 0/9 |
| HeadacheNervous system disorders | 0/5 | 1/8 | 1/9 |
| HypertensionVascular disorders | 0/5 | 1/8 | 0/9 |
| Event | Part 1: Vigil Alone | Part 1: Gemicitabine and Docetaxel | Part 2: Vigil Plus Temozolomide and Irinotecan |
|---|---|---|---|
| AnemiaBlood and lymphatic system disorders | 0/5 | 3/8 | 6/9 |
| VomitingGastrointestinal disorders | 0/5 | 2/8 | 6/9 |
| NauseaGastrointestinal disorders | 1/5 | 3/8 | 5/9 |
| DiarrheaGastrointestinal disorders | 0/5 | 0/8 | 5/9 |
| FatigueGeneral disorders | 1/5 | 3/8 | 5/9 |
| NeutropeniaBlood and lymphatic system disorders | 0/5 | 0/8 | 4/9 |
| AnorexiaMetabolism and nutrition disorders | 0/5 | 2/8 | 4/9 |
| Edema extremitiesGeneral disorders | 2/5 | 1/8 | 1/9 |
| ThrombocytopeniaBlood and lymphatic system disorders | 0/5 | 3/8 | 3/9 |
| Abdominal painGastrointestinal disorders | 0/5 | 0/8 | 3/9 |
All subjects registered to treatment
| Age, Categorical(Participants) | Part 1: Vigil Alone | Part 1: Gemicitabine and Docetaxel | Part 2: Vigil in Combination With Temozolomide and Irinotecan | Total |
|---|---|---|---|---|
| <=18 years | 0 | 4 | 3 | 7 |
| Between 18 and 65 years | 5 | 4 | 6 | 15 |
| >=65 years | 0 | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Part 1: Vigil Alone | Part 1: Gemicitabine and Docetaxel | Part 2: Vigil in Combination With Temozolomide and Irinotecan | Total |
|---|---|---|---|---|
| Female | 3 | 6 | 4 | 13 |
| Male | 2 | 2 | 5 | 9 |
| Ethnicity (NIH/OMB)(Participants) | Part 1: Vigil Alone | Part 1: Gemicitabine and Docetaxel | Part 2: Vigil in Combination With Temozolomide and Irinotecan | Total |
|---|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 1 | 3 |
| Not Hispanic or Latino | 4 | 7 | 8 | 19 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Part 1: Vigil Alone | Part 1: Gemicitabine and Docetaxel | Part 2: Vigil in Combination With Temozolomide and Irinotecan | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 1 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 |
| White | 5 | 7 | 9 | 21 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Part 1: Vigil Alone | Part 1: Gemicitabine and Docetaxel | Part 2: Vigil in Combination With Temozolomide and Irinotecan | Total |
|---|---|---|---|---|
| United States | 5 | 8 | 9 | 22 |
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Gradalis, Inc.