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

NCT01777594 | Completed Phase 2

• 1 other identifier: G-202-003
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Advanced Adult Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; HCC; liver; liver cancer; sorafenib

Outcome Measures

Primary Outcomes (1)

• Time to progression

  Duration of time from the first administration of G-202 to the time of radiologic progression

  every 8 weeks, until disease progression (estimated up to 2 years)

Secondary Outcomes (3)

• Overall response rate

  every 8 weeks, until disease progression (estimated up to 2 years)

• Progression-free survival

  every 8-12 weeks, until disease progression or death (estimated up to 3 years)

• Overall survival

  every 12 weeks for approximately 3 years or until patient death

Study Arms (1)

G-202 (Mipsagargin)

EXPERIMENTAL

G-202 (mipsagargin) administered by intravenous infusion on 3 consecutive days of a 28-day cycle

Drug: G-202

Interventions

G-202 DRUG

G-202 administered by intravenous infusion (IV, in the vein) on Days 1, 2 and 3 of each 28-day cycle until progression or development of unacceptable toxicity

Also known as: Mipsagargin

G-202 (Mipsagargin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GenSpera, Inc.: lead

Study Sites (4)

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

Oncology Consultants, PA

Houston, Texas, 77030, United States

Location

University of Texas Health Sciences Center at Houston, Memorial Hermann Cancer Center

Houston, Texas, 77030, United States

Location

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-3900, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Devalingam Mahalingam, M.D., Ph.D.

  University of Texas, Health Science Center, Cancer Therapy and Research Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2013
• First Posted: January 29, 2013
• Study Start: January 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: August 23, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)