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Dose-defining Study of Tirapazamine Combined With Embolization in Liver Cancer

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ClinicalTrials.gov Identifier: NCT02174549
Recruitment Status : Recruiting
First Posted : June 25, 2014
Last Update Posted : May 2, 2018
Sponsor:
Information provided by (Responsible Party):
Teclison Ltd.

Study Description
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Brief Summary:
This phase 1 study is to determine the optimal dose and tolerability of a hypoxia-activating agent, tirapazamine, when it is combined with embolization in liver cancer. Liver cancer patients who are Child-Pugh score A, suitable for embolization with tumor no more than 4 nodules are eligible. Tirapazamine will be given by intra-arterial injection before embolization. Treatment effect is evaluated by MRI based on mRECIST criteria. Repeat treatment is necessary only if disease progression. Expansion cohorts are open for metastatic gastrointestinal cancer and neuroendocrine tumor.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Gastrointestinal Cancer Metastatic Neuroendocrine Tumors Drug: Tirapazamine Procedure: Transarterial embolization (TAE) Phase 1 Phase 2

Detailed Description:
The study is a 3+3 design for dose escalation. Each cohort will have 3-6 patients based on tolerability. Patients will receive escalated doses of tirapazamine until maximally tolerated dose. Embolization is performed per standard practice using Lipiodol and Gelfoam under X-ray guidance. Once a suitable dose is determined, an expansion cohort of 15 patients will be treated with the recommended phase 2 dose to determine preliminary efficacy. Expansion cohorts include (1) hepatocellular carcinoma, (2) metastatic solid tumors with liver metastasis, and (3) neuroendocrine tumor. Adverse events are evaluated by CTCAE vs. 4.0 and efficacy is evaluated by MRI using modified RECIST criteria and RECIST criteria.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open label, dose escalation 3+3 design; 3 expansion cohorts: hepatocellular carcinoma, advanced solid tumors and neuroendocrine tumor.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Dose-Escalating Study of Combining Intravenous Tirapazamine and Transarterial Embolization (TAE) in Liver Cancer
Study Start Date : September 2014
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer
Drug Information available for: Lipiodol

Arms and Interventions
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Arm Intervention/treatment
Experimental: Tirapazamine
Administration with dose escalated tirapazamine before embolization until maximally tolerated dose achieved.
 Drug: Tirapazamine
Intra-arterial injection into the tumor feeding artery

Procedure: Transarterial embolization (TAE)
Lipiodol and Gelfoam used to embolize tumor vessels and induce tumor hypoxia
Other Name: Lipiodol and Gelfoam as the standard embolizing agents.


Outcome Measures
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Primary Outcome Measures :
  1. determine the recommended phase 2 dose [ Time Frame: 2 years ]
    future dose used for randomzied trials


Secondary Outcome Measures :
  1. Complete Response (CR) rate [ Time Frame: 2 years ]
    mRECIST based on mRECIST

  2. Duration of response [ Time Frame: 2 years ]
    From randomization to progression


Other Outcome Measures:
  1. Area under the plasma concentration versus time curve (AUC) [ Time Frame: 2 years ]
    PK parameter


Eligibility Criteria
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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • Confirmed diagnosis of HCC > 10 mm with a characteristic 4-phase CT or dynamic contrast enhanced MRI finding showing intense arterial uptake followed by "washout" of contrast in the venous-delayed phases per American Association for the Study of Liver Disease (AASLD) criteria.
  • Patients between ages 20 and 80
  • Patients with single or multiple (2-4 nodules) HCC who are unsuitable or unwilling for surgical resection or RFA. The largest tumor nodule should be less than 10 cm in the largest diameter. The total volume of tumor cannot exceed 50% of liver; or patients with liver metastatic gastrointestinal cancer, including neuroendocrine tumor
  • Patients are candidates for TAE or Transarterial ChemoEmbolization (TACE). No tumor invasion to portal vein or thrombosis in portal vein.
  • ECOG score 0-1 with no known cardiac, pulmonary or renal dysfunction
  • Child-Pugh score group A or B7 liver functional score
  • Prior local therapies such as surgical resection, radiofrequency ablation, or alcohol injection are allowed as long as tumor progresses from the prior treatment and the patients are still candidates for TAE. All prior therapy must be at least 4 weeks prior to enrollment and free from treatment-related toxicity.
  • No TAE/TACE in the past
  • Patients have normal organ function: ANC ≥ 1000 /µL, Hemoglobin ≥ 9 gm/dL, Platelets ≥ 50,000 /µL, Creatinine ≤ 2 mg/dL, AST and ALT < 5 X upper normal limit of the current institution; bilirubin ≤ 3.0 mg/dL, PT prolongation no more than 4 sec above upper limit of normal.

For the expansion cohort of neuroendocrine tumor or metastatic gastrointestinal cancer

  • Unresectable, locally advanced or metastatic, well differentiated (low or intermediate grade), neuroendocrine tumors (NET).
  • Liver metastatic gastrointestinal cancer.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02174549


Contacts
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Contact: Linta Garcia, PhD linta_garcia@teclison.com
Contact: Ray Lee, MD PhD ray.lee01@teclison.com

Locations
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United States, California
University of California Irvine Medical Center Recruiting
Orange, California, United States, 92868
Contact: Jennifer Berg    714-456-7687    jdberg@uci.edu   
Univ. of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Curt Johnson    415-353-2310    curt.johanson@ucsf.edu   
Sponsors and Collaborators
Teclison Ltd.
Investigators
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Principal Investigator: Nadine Abi-Jaoudeh, MD Univ. of California, Irvine
More Information
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Responsible Party: Teclison Ltd.
ClinicalTrials.gov Identifier: NCT02174549     History of Changes
Other Study ID Numbers: LT001
First Posted: June 25, 2014    Key Record Dates
Last Update Posted: May 2, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Teclison Ltd.:
Hypoxia
Embolization
Tirapazamine

Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Liver Neoplasms
Neuroendocrine Tumors
Gastrointestinal Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
 Liver Diseases
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Gastrointestinal Diseases
Ethiodized Oil
Tirapazamine
Gelatin Sponge, Absorbable
Antineoplastic Agents
Hemostatics
Coagulants