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| ID | Type | Description | Link |
|---|---|---|---|
| R01FD005077 | U.S. FDA Grant/Contract | View source |
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| Name | Class |
|---|---|
| Food and Drug Administration (FDA) | FED |
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This study will evaluate if a drug called G-202 can be safely used to treat people with glioblastoma (GBM) that has progressed or recurred. G-202 is given by intravenous infusion on three consecutive days of a 28-day cycle.
Glioblastoma (GBM) comprises about 16% of all malignancies of the nervous system and over 50% of all gliomas. Standard of care for newly-diagnosed GBM is a combination of surgical debulking followed by concurrent radiotherapy and chemotherapy with temozolomide. Efforts to improve second-line therapy in GBM have met with only marginal success and there is a large unmet medical need for new therapies. G-202 (mipsagargin) is an example of prodrug chemotherapy. It is activated by Prostate Specific Membrane Antigen (PSMA), which is expressed by some cancer cells and in the blood vessels of most solid tumors, including GBM, but not by normal cells or blood vessels in normal tissue. It is believed that activation of the prodrug G-202 will allow the drug to kill cancer cells. This study will evaluate the activity, safety and CNS exposure of G-202 in participants with recurrent or progressive GBM receiving G-202 by intravenous infusion on three consecutive days of a 28-day cycle. Funding Source - FDA Office of Orphan Products Development (OOPD)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| G-202 (Mipsagargin) | Experimental | G-202 (Mipsagargin) administered by intravenous infusion on 3 consecutive days of a 28-day cycle |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| G-202 | Drug | G-202 administered by intravenous infusion (IV, in the vein) on Days 1, 2 and 3 of each 28-day cycle until progression or development of unacceptable toxicity |
|
| Measure | Description | Time Frame |
|---|---|---|
| 6-month Progression-free Survival (PFS) | Percentage of patients who received at least 2 cycles of G-202 and have not progressed or died within 6 months of beginning treatment with G-202. Progression is defined using Response Assessment in Neuro-Oncology Working Group (RANO) for high-grade glioma, as any of the following: by any of the following: 25% or greater increase in sum of the products of perpendicular diameters of enhancing lesions (compared with baseline if no decrease) on stable or increasing doses of corticosteroids; a significant increase in T2/FLAIR nonenhancing lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy, not due to comorbid events; the appearance of any new lesions; clear progression of nonmeasurable lesions; or definite clinical deterioration not attributable to other causes apart from the tumor, or to decrease in corticosteroid dose. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Toxicity Assessed by CTCAE v 4.03 Criteria | Percentage of all analyzed patients experiencing treatment-emergent adverse events. | Every 2 weeks for approximately one year |
| Objective Tumor Response Rate |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Piccioni, M.D., Ph.D. | University of California, San Diego Moores Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Diego Moores Cancer Center | La Jolla | California | 92093 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | G-202 (Mipsagargin) | G-202 (Mipsagargin) administered by intravenous infusion on 3 consecutive days of a 28-day cycle G-202: G-202 administered by intravenous infusion (IV, in the vein) on Days 1, 2 and 3 of each 28-day cycle until progression or development of unacceptable toxicity |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | G-202 (Mipsagargin) | G-202 (Mipsagargin) administered by intravenous infusion on 3 consecutive days of a 28-day cycle G-202: G-202 administered by intravenous infusion (IV, in the vein) on Days 1, 2 and 3 of each 28-day cycle until progression or development of unacceptable toxicity |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 6-month Progression-free Survival (PFS) | Percentage of patients who received at least 2 cycles of G-202 and have not progressed or died within 6 months of beginning treatment with G-202. Progression is defined using Response Assessment in Neuro-Oncology Working Group (RANO) for high-grade glioma, as any of the following: by any of the following: 25% or greater increase in sum of the products of perpendicular diameters of enhancing lesions (compared with baseline if no decrease) on stable or increasing doses of corticosteroids; a significant increase in T2/FLAIR nonenhancing lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy, not due to comorbid events; the appearance of any new lesions; clear progression of nonmeasurable lesions; or definite clinical deterioration not attributable to other causes apart from the tumor, or to decrease in corticosteroid dose. | response-evaluable participants | Posted | Count of Participants | Participants | 6 months |
|
one year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | G-202 (Mipsagargin) | G-202 (Mipsagargin) administered by intravenous infusion on 3 consecutive days of a 28-day cycle G-202: G-202 administered by intravenous infusion (IV, in the vein) on Days 1, 2 and 3 of each 28-day cycle until progression or development of unacceptable toxicity |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. David Piccioni | University of California, San Diego Moores Cancer Center | 858-657-7000 | dpiccioni@ucsd.edu |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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|
Percentage of analyzed participants experiencing a complete response (CR) or partial response (PR) using RANO criteria. CR is defined as complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions; and patient must be off corticosteroids or on physiologic replacement doses only, and stable or improved clinically. PR is defined as at least 50% decrease, compared with baseline, in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; no progression of nonmeasurable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and patient must be on a corticosteroid dose not greater than the dose at time of baseline scan and is stable or improved clinically.
| approximately one year |
| Duration of PFS | Duration of time from the first administration of G-202 until the first documented progression or date of death, assessed up to 12 months. Progression is defined using Response Assessment in Neuro-Oncology Working Group (RANO) for high-grade glioma, as any of the following: by any of the following: 25% or greater increase in sum of the products of perpendicular diameters of enhancing lesions (compared with baseline if no decrease) on stable or increasing doses of corticosteroids; a significant increase in T2/FLAIR nonenhancing lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy, not due to comorbid events; the appearance of any new lesions; clear progression of nonmeasurable lesions; or definite clinical deterioration not attributable to other causes apart from the tumor, or to decrease in corticosteroid dose. | Every 4 weeks for approximately one year |
| Overall Survival | Duration of time from the first administration of G-202 until the date of death, assessed up to 12 months | Every 4 weeks for approximately one year |
| Biomarkers in Tumor | PSMA immunohistochemistry staining score on tumor tissue collected prior to start of G-202 study treatment. Intensity of staining was ranked on a scale of 0, 1, 2, or 3 (with 0 representing no staining and 3 representing maximum intensity): absence of staining (0), weak staining (1), medium staining (2), or strong staining (3) relative to a staining calibration curve and normalized to the image mean background intensity. The scoring scale does not have a title nor does it have a subscale. It is not known whether PSMA staining intensity is associated with tumor molecular phenotypes or response outcome to G-202; therefore, this was an exploratory analysis. However, the lack of objective tumor response in the trial precluded comparative analysis. | Within 4 weeks of receiving G-202 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| G-202 (Mipsagargin) |
G-202 (Mipsagargin) administered by intravenous infusion on 3 consecutive days of a 28-day cycle G-202: G-202 administered by intravenous infusion (IV, in the vein) on Days 1, 2 and 3 of each 28-day cycle until progression or development of unacceptable toxicity |
|
|
| Secondary | Toxicity Assessed by CTCAE v 4.03 Criteria | Percentage of all analyzed patients experiencing treatment-emergent adverse events. | Posted | Count of Participants | Participants | Every 2 weeks for approximately one year |
|
|
|
| Secondary | Objective Tumor Response Rate | Percentage of analyzed participants experiencing a complete response (CR) or partial response (PR) using RANO criteria. CR is defined as complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions; and patient must be off corticosteroids or on physiologic replacement doses only, and stable or improved clinically. PR is defined as at least 50% decrease, compared with baseline, in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; no progression of nonmeasurable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and patient must be on a corticosteroid dose not greater than the dose at time of baseline scan and is stable or improved clinically. | response-evaluable participants | Posted | Count of Participants | Participants | approximately one year |
|
|
|
| Secondary | Duration of PFS | Duration of time from the first administration of G-202 until the first documented progression or date of death, assessed up to 12 months. Progression is defined using Response Assessment in Neuro-Oncology Working Group (RANO) for high-grade glioma, as any of the following: by any of the following: 25% or greater increase in sum of the products of perpendicular diameters of enhancing lesions (compared with baseline if no decrease) on stable or increasing doses of corticosteroids; a significant increase in T2/FLAIR nonenhancing lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy, not due to comorbid events; the appearance of any new lesions; clear progression of nonmeasurable lesions; or definite clinical deterioration not attributable to other causes apart from the tumor, or to decrease in corticosteroid dose. | response-evaluable participants | Posted | Median | 95% Confidence Interval | months | Every 4 weeks for approximately one year |
|
|
|
| Secondary | Overall Survival | Duration of time from the first administration of G-202 until the date of death, assessed up to 12 months | response-evaluable participants | Posted | Median | 95% Confidence Interval | months | Every 4 weeks for approximately one year |
|
|
|
| Secondary | Biomarkers in Tumor | PSMA immunohistochemistry staining score on tumor tissue collected prior to start of G-202 study treatment. Intensity of staining was ranked on a scale of 0, 1, 2, or 3 (with 0 representing no staining and 3 representing maximum intensity): absence of staining (0), weak staining (1), medium staining (2), or strong staining (3) relative to a staining calibration curve and normalized to the image mean background intensity. The scoring scale does not have a title nor does it have a subscale. It is not known whether PSMA staining intensity is associated with tumor molecular phenotypes or response outcome to G-202; therefore, this was an exploratory analysis. However, the lack of objective tumor response in the trial precluded comparative analysis. | Only 11 samples of tumor tissue collected prior to the start of study treatment (G-202) were available for immunohistochemistry. PSMA staining was not an eligibility criterion. | Posted | Median | Standard Deviation | score on a scale | Within 4 weeks of receiving G-202 |
|
|
|
| 22 |
| 26 |
| 6 |
| 26 |
| 24 |
| 26 |
| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Symptomatic Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Infusion reaction | General disorders | Systematic Assessment |
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| Creatinine increased | Investigations | Systematic Assessment |
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| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Cerebral edema | Nervous system disorders | Systematic Assessment |
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| Depressed level of consciousness | Nervous system disorders | Systematic Assessment |
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| Seizure | Nervous system disorders | Systematic Assessment |
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| Vertebral dissection | Nervous system disorders | Systematic Assessment |
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| Aspiration of vomit | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Respiratory failure due to vomiting | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Fever | General disorders | Systematic Assessment |
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| ALT increased | Investigations | Systematic Assessment |
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| AST increased | Investigations | Systematic Assessment |
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| Creatinine increased | Investigations | Systematic Assessment |
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| Platelet count decreased | Investigations | Systematic Assessment |
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| PTT prolonged | Investigations | Systematic Assessment |
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| White blood cells decreased | Investigations | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Seizure | Nervous system disorders | Systematic Assessment |
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| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Depression | Psychiatric disorders | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Hypotension | Vascular disorders | Systematic Assessment |
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| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |