Study of G-202 (Mipsagargin) as Second-Line Therapy Following Sorafenib in Hepatocellular Carcinoma (G-202-003)

GenSpera

Status and phase

Completed

Phase 2

Conditions

Advanced Adult Hepatocellular Carcinoma

Treatments

Drug: G-202

Study type

Interventional

Funder types

Industry

Identifiers

NCT01777594

G-202-003

Details and patient eligibility

About

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer worldwide and the third most common cause of death from cancer. Sorafenib is the only approved therapy for treatment of advanced HCC, and there is a need to identify more drugs that are beneficial for these patients without unacceptable side effects. Prodrug chemotherapy is an approach in which an inactive non-toxic agent is administered to the patient and gets activated within the body at specific locations, resulting in a higher concentration of the cytotoxic form at a tumor location while avoiding general side effects. G-202 (mipsagargin) is an example of prodrug chemotherapy. It is activated by Prostate Specific Memory Antigen (PSMA), which is expressed by some cancer cells and in the blood vessels of most solid tumors, 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 and safety of G-202 in patients with hepatocellular carcinoma who have progressed after taking sorafenib. The study will evaluate clinical activity and safety of G-202 administered by intravenous infusion on three consecutive days of a 28-day cycle.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Informed consent document signed prior to the performance of any study-specific procedures and initiation of study therapy
At least 18 years of age
ECOG Performance Status 0 or 1
Histologic or cytologic confirmation of hepatocellular carcinoma (HCC)
Child-Pugh score of A or B7
At least one measurable lesion (preferably in the liver) assessed within 4 weeks of first administration of G-202 by abdominal CT or MRI with dynamic phase imaging of the liver, pelvic CT or MRI with contrast, chest CT with contrast, and bone imaging in patients with known bone metastases or if medically indicated
Must have received sorafenib therapy and had disease progression on sorafenib therapy or was not able to tolerate sorafenib
Sorafenib or other anti-cancer therapy must have been discontinued > 21days prior to the first administration of G-202
Adequate hematologic function (ANC ≥ 1200/mm3, hemoglobin ≥ 8.5 g/dL, platelet count ≥ 75,000/mm3)
Adequate hepatic function (albumin ≥ 2.8 g/dL, AST and ALT ≤ 5 x ULN, total bilirubin < 2 mg/dL)
Adequate renal function (proteinuria level ≤ 2+, serum creatinine ≤ 1.5 x ULN)
Acceptable coagulation profile (PT/INR ≤ 2.3, aPTT ≤ 1.5 x ULN)
Acute toxicity from previous therapy (excluding alopecia) must have resolved to ≤ Grade 1 per CTCAE v4.0
Negative serum pregnancy test for women of child-bearing potential

Exclusion criteria

Prior locoregional therapies (e.g., transarterial chemoembolization [TACE]) ≤ 4 weeks prior to the first administration of G-202 or not recovered from treatment-related toxicities.
Radiotherapy ≤ 4 weeks prior to the first administration of G-202 or not recovered from toxicities (palliative radiotherapy for bone lesions ≤ 2 weeks prior allowed)
Major surgery ≤ 4 weeks prior to first administration of G-202
Intolerance to both CT and MRI contrast agents
Candidate for liver transplantation
Persistent or untreated biliary infection
Any GI bleeding within 12 weeks prior to first administration of G-202
Currently receiving any full-dose anti-coagulation treatment
Clinically-significant third space fluid accumulation
Known CNS metastasis, including brain metastasis or leptomeningeal metastasis
Known human immunodeficiency virus (HIV) positivity
Viral hepatitis requiring anti-viral therapy
History or evidence of cardiac risk, including screening QTc interval > 470 msec, clinically-significant uncontrolled arrhythmias or arrhythmia requiring treatment (except atrial fibrillation and paroxysmal supraventricular tachycardia), history of acute coronary syndromes within 6 months (including myocardial infarction and unstable angina, coronary artery bypass graft, angioplasty, or stenting) or history of congestive heart failure with most recent ejection fraction < 45%
Uncontrolled hypertension (systolic BP ≥ 160 or diastolic BP ≥ 100)
Cerebrovascular accident or transient ischemic attack within 6 months prior to the first dose of study therapy
History of pulmonary embolism within 6 months or untreated deep venous thrombosis
Documentation of keratosis follicularis (also known as Darier or Darier-White disease)
Requirement for chronic use of inhibitors or inducers of cytochrome (CYP3A4) iso-enzymes
Known hypersensitivity to any study drug component, including thapsigargin derivatives, polysorbate 20, or propylene glycol
Known history of another primary malignancy that has not been in remission for at least 2 years (non-melanoma skin cancer, cervical carcinoma in situ or squamous intraepithelial lesions allowed)
Use of any investigational agent within 4 weeks prior to the first administration of G-202
Pregnancy or nursing
Any medical intervention, other medical condition, psychiatric condition or social circumstance which could compromise patient safety and/or adherence with study requirements