We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dose-Escalation Phase 1 Study of G-202 (Mipsagargin) in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01056029
Recruitment Status : Completed
First Posted : January 26, 2010
Last Update Posted : December 10, 2015
Sponsor:
Information provided by (Responsible Party):
GenSpera, Inc.

Tracking Information
First Submitted Date  ICMJE January 25, 2010
First Posted Date  ICMJE January 26, 2010
Last Update Posted Date December 10, 2015
Study Start Date  ICMJE January 2010
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2010)
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2010)
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-Escalation Phase 1 Study of G-202 (Mipsagargin) in Patients With Advanced Solid Tumors
Official Title  ICMJE An Open Label, Single-Arm, Dose-Escalation Phase 1 Study of G-202 (Mipsagargin) in Patients With Advanced Solid Tumors
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE Drug: G-202
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
Study Arms  ICMJE Experimental: G-202
Intervention: Drug: G-202
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: January 25, 2010)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2013
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01056029
Other Study ID Numbers  ICMJE G-202-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party GenSpera, Inc.
Original Responsible Party Russell Richerson Chief Operating Officer, GenSpera Inc
Current Study Sponsor  ICMJE GenSpera, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: George Wilding, M.D University of Wisconsin, Madison
Principal Investigator: Michael Carducci, M.D. Johns Hopkins University
Principal Investigator: Devalingam Mahalingam, MD University of Texas, Health Science Center,Cancer Therapy and Research Center
PRS Account GenSpera, Inc.
Verification Date December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP