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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GenSpera, Inc.
ClinicalTrials.gov Identifier:
NCT01777594
First received: January 18, 2013
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

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 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.


Condition Intervention Phase
Advanced Adult Hepatocellular Carcinoma
Drug: G-202
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Single-Arm Study of G-202 as Second-Line Therapy Following Sorafenib for Adult Patients With Progressive Advanced Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by GenSpera, Inc.:

Primary Outcome Measures:
  • Time to progression [ Time Frame: every 8 weeks, until disease progression (estimated up to 2 years) ] [ Designated as safety issue: No ]
    Duration of time from the first administration of G-202 to the time of radiologic progression


Secondary Outcome Measures:
  • Overall response rate [ Time Frame: every 8 weeks, until disease progression (estimated up to 2 years) ] [ Designated as safety issue: No ]
    Percentage of patients with complete response (CR), partial response (PR) or stable disease (SD) after treatment with G-202

  • Progression-free survival [ Time Frame: every 8-12 weeks, until disease progression or death (estimated up to 3 years) ] [ Designated as safety issue: No ]
    Duration of time from the first administration of G-202 to the time of radiologic progression or death

  • Overall survival [ Time Frame: every 12 weeks for approximately 3 years or until patient death ] [ Designated as safety issue: No ]
    Duration of time from the first administration of G-202 to the time of death


Estimated Enrollment: 29
Study Start Date: January 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: G-202
G-202 administered by intravenous infusion on 3 consecutive days of a 28-day cycle
Drug: G-202
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01777594

Locations
United States, Texas
Mary Crowley Cancer Research Center
Dallas, Texas, United States, 75230
Oncology Consultants, PA
Houston, Texas, United States, 77030
University of Texas Health Sciences Center at Houston, Memorial Hermann Cancer Center
Houston, Texas, United States, 77030
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
Sponsors and Collaborators
GenSpera, Inc.
Investigators
Study Chair: Devalingam Mahalingam, M.D., Ph.D. University of Texas, Health Science Center, Cancer Therapy and Research Center
  More Information

No publications provided

Responsible Party: GenSpera, Inc.
ClinicalTrials.gov Identifier: NCT01777594     History of Changes
Other Study ID Numbers: G-202-003
Study First Received: January 18, 2013
Last Updated: October 9, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by GenSpera, Inc.:
hepatocellular carcinoma
HCC
liver
liver cancer
sorafenib

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014