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An Open_Label, Single-Arm,Dose-Escalation Phase 1 Study of G-202 in Patients With Advanced Solid Tumors

Phase 1
18 Years
Open (Enrolling)
Advanced Solid Tumors

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Trial Information

An Open_Label, Single-Arm,Dose-Escalation Phase 1 Study of G-202 in Patients With Advanced Solid Tumors

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 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.

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

- 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

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

George Wilding, M.D

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Wisconsin, Madison


United States: Food and Drug Administration

Study ID:




Start Date:

January 2010

Completion Date:

March 2013

Related Keywords:

  • Advanced Solid Tumors
  • Solid Tumors
  • Neoplasms



Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
University of Texas, Health Science Center,Cancer Therapy and Research CenterSan Antonio, Texas  78229
University of Wisconsin Paul P Carbone Comprehensive Cancer CenterMadison, Wisconsin  53792