An Open Label, Single-Arm, Dose-Escalation Phase 1 Study of G-202 (Mipsagargin) in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- G-202
- Conditions
- Advanced Solid Tumors
- Sponsor
- GenSpera, Inc.
- Enrollment
- 30
- Locations
- 3
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
This is an open-label, single-arm, dose-escalation Phase I study to determine the maximum tolerated dose (MTD) of G-202 (mipsagargin) when administered once daily for 3 consecutive days of a 28-day cycle in patients with advanced solid tumors. G-202 will be administered by intravenous infusion over 1 hour on Days 1, 2 and 3 of each 28-day cycle.
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
G-202
Intervention: G-202
Outcomes
Primary Outcomes
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
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
Establish the recommended dose of G-202 to be used in Phase II studies.
Time Frame: 2 years
Secondary Outcomes
- 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.(2 years)
- Document any evidence of anti-tumor activity, including response rate, disease stability, progression-free or overall survival, in response to G-202 administration(2 years)