- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01056029
Dose-Escalation Phase 1 Study of G-202 (Mipsagargin) in Patients With Advanced Solid Tumors
An Open Label, Single-Arm, Dose-Escalation Phase 1 Study of G-202 (Mipsagargin) in Patients With Advanced Solid Tumors
Study Overview
Detailed Description
Pro-drug chemotherapy is an approach to cancer treatment that is being investigated as a means to achieve higher concentrations of cytotoxic or biologically active agents at a tumor location while avoiding systemic toxicity. With pro-drug chemotherapy, a relatively non-toxic form of a cytotoxin, the pro-drug, is converted into the active cytotoxic agent at the tumor site or other specific location. G-202 (mipsagargin) is a thapsigargin pro-drug; it consists of a cytotoxic analog of thapsigargin coupled to a masking peptide which inhibits its biologic activity until proteolytic cleavage at the tumor site. Thapsigargin is a natural product with profound effects on cell viability. Thapsigargin is a non-cell-type specific toxin with documented ability to kill a broad spectrum of cancer cell lines as well as normal endothelial cells, fibroblasts and osteoblasts. It induces a rapid and pronounced increase in the concentration of cytosolic calcium, due to blockade of the Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase (SERCA) pump to which it binds with high affinity. The increase in cytosolic calcium leads to induction of apoptosis and ensuing cell death.
The anti-tumor effect of G-202 in humans with advanced solid tumors is not yet known.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21231
- Sidney kimmel comprehensive cancer center at johns hopkins
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Texas
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San Antonio, Texas, United States, 78229
- University of Texas, Health Science Center,Cancer Therapy and Research Center
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Wisconsin
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Madison, Wisconsin, United States, 53792
- University of Wisconsin Paul P Carbone Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically-confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
- Disease that is measurable and/ or evaluable by RECIST criteria. Patients with prostate cancer require presence of disease on bone scan and/or CT scan and evidence of increasing PSA after standard hormonal therapy
- ECOG Performance Status ≤ 2
- Life expectancy estimated to be at least 3 months
Acceptable liver function:
- In the absence of disease involvement in the liver and if bilirubin ≤ 1.5 times institutional upper limit of normal (ULN), AST (SGOT), ALT (SGPT) and GGT may be ≤ 2 times ULN
- In the presence of disease involvement in the liver and if bilirubin ≤ 1.5 times institutional upper limit of normal (ULN), AST (SGOT), ALT (SGPT) and GGT may be ≤ 5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN Patients with bone metastases alkaline phosphatases ≤ 5 times ULN
Acceptable renal function:
- Serum creatinine ≤ 1.5 times ULN, OR
- Calculated creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula)
Acceptable hematologic status:
- Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
- Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
- Hemoglobin ≥ 9 g/dL
- Urinalysis with no evidence of proteinuria
- Acceptable coagulation profile (PT or INR, PTT) < 1.5 times ULN
- At least 4 weeks since prior chemotherapy or surgery, with recovery to Grade 1 or baseline of significant toxicities felt related to prior drug(s)
- Women of childbearing potential must have a negative serum pregnancy test at screening.
- All patients (males and females) of child-bearing potential must agree to use an effective method of birth control
- Ability to understand and willingness to sign a written informed consent document
- Patients with prostate cancer must continue androgen deprivation therapy with LHRH agonists
Exclusion Criteria:
- Documentation of keratosis follicularis, also known as Darier or Darier-White disease
- Known hypersensitivity to any study drug component, including thapsigargin derivatives, Polysorbate 20, or propylene glycol
- Patients with known and untreated brain metastases. Patients with brain metastases that have been treated and demonstrated to be clinically stable for at least 30 days may be enrolled onto the study
- Patients with a family history of coagulopathy or patients with DVT or pulmonary embolus within the last 6 months
- Patients taking anti-coagulants that include Coumadin or low molecular weight heparin
Patients with pre-existing cardiac conditions:
- Prior documented myocardial infarction within the last 6 months
- Pre-existing cardiac failure (NYHA class III-IV)
- Atrial fibrillation on anti-coagulants
- Unstable angina
- Severe valvulopathy
- Cardiac angioplasty or stenting within the last 6 months
- Use or requirement for use of inhibitors or inducers of cytochrome isoenzymes
- Corrected QTc prolongation value, calculated using Bazett's formula (QTcB = QT/RR ½), > 450 msec
- Pregnant or lactating females
- Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
- Active uncontrolled infection, including known history of AIDS or hepatitis B or C
- Any psychological, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
- Concurrently receiving any other investigational agents while on study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: G-202
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Thapsigargin is Pro-drug chemotherapy which will be administered by intravenous infusion over 1 hour on Days, 1, 2 and 3 of each 28 day cycle
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Determine the MTD and DLT(s) of G-202 administered by intravenous infusion daily for 3 consecutive days on a 28-day cycle in patients with advanced solid tumors.
Time Frame: 2 years
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2 years
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Establish the recommended dose of G-202 to be used in Phase II studies.
Time Frame: 2 years
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2 years
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Determine the pharmacokinetics of G-202 administered by intravenous infusion daily for 3 consecutive days on a 28-day cycle in patients with advanced solid tumors.
Time Frame: 2 years
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2 years
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Investigate the safety profile of G-202 administered by intravenous infusion daily for 3 consecutive days on a 28-day cycle in patients with advanced solid tumors.
Time Frame: 2 years
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2 years
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Document any evidence of anti-tumor activity, including response rate, disease stability, progression-free or overall survival, in response to G-202 administration
Time Frame: 2 years
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2 years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: George Wilding, M.D, University of Wisconsin, Madison
- Principal Investigator: Devalingam Mahalingam, MD, University of Texas, Health Science Center,Cancer Therapy and Research Center
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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AmgenCompletedCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced MalignancyUnited States, Australia
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NantCell, Inc.CompletedQUILT-2.016: Study of AMG 479 With Biologics or Chemotherapy for Subjects With Advanced Solid TumorsCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced Malignancy
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Incyte Biosciences Japan GKCompletedAdvanced Solid Tumors | Metastatic Solid TumorsJapan
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Memorial Sloan Kettering Cancer CenterKyowa Hakko Kirin Pharma, Inc.CompletedAdvanced Solid Tumors | Metastatic Solid TumorsUnited States
-
Bristol-Myers SquibbCompletedAdvanced Solid Tumors | Metastatic Solid TumorsKorea, Republic of, Canada, Australia
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Vividion Therapeutics, Inc.RecruitingAdvanced Solid Tumors | Advanced Hematologic TumorsUnited States, Australia
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Hoffmann-La RocheCompletedSolid Tumors, Advanced Solid TumorsUnited States
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Esperance Pharmaceuticals IncCompletedAdvanced Solid Tumors | Solid TumorsUnited States
-
Millennium Pharmaceuticals, Inc.CompletedAdvanced Solid Tumors, Neoplasms, Advanced SolidHungary
Clinical Trials on G-202
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GenSpera, Inc.Saint John's Cancer InstituteWithdrawn
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GenSpera, Inc.CompletedGlioblastoma MultiformeUnited States
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GenSpera, Inc.CompletedClear Cell Renal Cell CarcinomaUnited States
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GenSpera, Inc.CompletedProstatic NeoplasmsUnited States
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GenSpera, Inc.CompletedAdvanced Adult Hepatocellular CarcinomaUnited States
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Immune-Onc TherapeuticsCalifornia Institute for Regenerative Medicine (CIRM)RecruitingCMML | AML With Monocytic DifferentiationUnited States
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Shanghai Zerun Biotechnology Co.,LtdWalvax Biotechnology Co., Ltd.Active, not recruiting