Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 39 of 70 for:    "advanced liver cancer"

Combination of TATE and PD-1 Inhibitor in Liver Cancer (TATE-PD1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03259867
Recruitment Status : Active, not recruiting
First Posted : August 24, 2017
Last Update Posted : September 11, 2019
Sponsor:
Information provided by (Responsible Party):
Teclison Ltd.

Brief Summary:
This is a single center, open-label phase IIA study that investigates the preliminary efficacy of Trans-arterial Tirapazamine Embolization (TATE) treatment of liver cancer followed by a PD-1 checkpoint inhibitor (either nivolumab or pembrolizumab). Patients with four types of cancers will be enrolled, hepatocellular carcinoma (HCC), metastatic colorectal cancer (mCRC), metastatic gastric cancer and advanced non-small cell lung cancer. All enrolled patients need to have liver lesions.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Colorectal Neoplasms Gastric Cancer Lung Cancer Drug: Opdivo Injectable Product or Keytruda Injectable Product Combination Product: Trans-arterial tirapazamine embolization Phase 2

Detailed Description:
The goal of the study is to investigate whether tumor necrosis induced by Trans-arterial Tirapazamine Embolization (TATE) treatment can boost anti-tumor immunity and enhance the therapeutic efficacy of immune checkpoint inhibitor. Patients with advanced liver cancers (primary HCC or metastatic liver cancer derived from colorectal, gastric and NSCLC) will be enrolled in the study. Liver lesions will be treated with up to 4 TATE treatments for optimal debulking, which also serve as a vaccination process toward tumor. Lesion not treated with TATE will be used for monitoring the response toward a PD-1 inhibitor (either Nivolumab or Pembrolizumab per investigator decision). If a patient subsequently develops an "escape" to the PD-1 inhibitor, patient can have another 2 TATE treatments of the escaped tumor lesion. Dosing of the PD-1 inhibitor is per standard FDA-approved dosing schedule and continues until progressive disease. The efficacy will be assessed by the response rate (RR) using RECIST and irRC for the non-TATE treated lesion, and compared with the historic RR of the PD-1 inhibitor in HCC (~16%) and mCRC (almost 0% for those without mismatch repair defect), advanced gastric cancer (15%) and metastatic NSCLC who failed to respond to an immune checkpoint inhibitor.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: One arm for HCC, CRC, gastric cancer and NSCLC each. All enrolled patients will receive the same treatment with TATE and a PD-1 inhibitor until disease progression
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IIA Single-Arm Study of Treatment of Patients With Advanced Liver Cancer With a Combination of TATE (Transarterial Tirapazamine Embolization) Followed by an Anti-PD-1 Monoclonal Antibody
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : October 30, 2020
Estimated Study Completion Date : December 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Arm Intervention/treatment
Experimental: Hepatocellular carcinoma

PD-1 inhibitor (either Opdivo 240 mg Q2W IV or Keytruda 200 mg Q3W IV) starts at day 1, and continues until progression.

TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.

Drug: Opdivo Injectable Product or Keytruda Injectable Product
a PD-1 immune check inhibitor per Investigator decision

Combination Product: Trans-arterial tirapazamine embolization
Embolization with Lipiodol and Gelfoam

Experimental: Colorectal cancer

PD-1 inhibitor (Keytruda 200 mg Q3W IV) starts at day 1, and continues until progression.

TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.

Drug: Opdivo Injectable Product or Keytruda Injectable Product
a PD-1 immune check inhibitor per Investigator decision

Combination Product: Trans-arterial tirapazamine embolization
Embolization with Lipiodol and Gelfoam

Experimental: Gastric cancer

PD-1 inhibitor (Keytruda 200 mg Q3W IV) starts at day 1, and continues until progression.

TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.

Drug: Opdivo Injectable Product or Keytruda Injectable Product
a PD-1 immune check inhibitor per Investigator decision

Combination Product: Trans-arterial tirapazamine embolization
Embolization with Lipiodol and Gelfoam

Experimental: NSCLC

PD-1 inhibitor (Keytruda 200 mg Q3W IV) starts at day 1, and continues until progression.

TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.

Drug: Opdivo Injectable Product or Keytruda Injectable Product
a PD-1 immune check inhibitor per Investigator decision

Combination Product: Trans-arterial tirapazamine embolization
Embolization with Lipiodol and Gelfoam




Primary Outcome Measures :
  1. Response rate [ Time Frame: up to 24 months ]
    Objective response rate in non-TATE treated lesion


Secondary Outcome Measures :
  1. Overall Response rate [ Time Frame: up to 24 months ]
    All tumor lesions

  2. Duration of Response [ Time Frame: up to 24 months ]
    All tumor lesions

  3. Progression Free Survival [ Time Frame: up to 24 months ]
    From randomization to disease progression or death

  4. Overall survival [ Time Frame: through study completion, an average of 3 years ]
    From randomization to death



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with either a confirmed diagnosis of (1) metastatic colorectal cancer in liver based on histopathology of either a prior resection of primary lesion or a biopsied liver metastatic lesion; (2) advanced HCC (BCLC-stage C) with a characteristic 3 or 4-phase CT or dynamic contrast enhanced MRI finding showing arterial uptake followed by "washout" of contrast in the venous-delayed phases per American Association for the Study of Liver Disease (AASLD) criteria; (3) metastatic gastric cancer; (4) metastatic NSCLC without EGFR or ALK mutation.
  2. Patients between ages 18 and 80
  3. If HCC patients, they should have progressive disease (PD) on intolerant of or refusing sorafenib. If mCRC, they should have received at least one regimen of 5-fluouracil based systemic chemotherapy such as FOLFOX, FOLFIRI, CAPOX, or XELOX, with or without a VEGF or EGFR receptor inhibitor. For patients with metastatic gastric cancer, they should have failed at least one line of systemic chemotherapy. For patients with NSCLC, they should have been treated with a PD-1 inhibitor (either with or without chemotherapy) for at least 4 months but are not able to achieve a response.
  4. Patients with at least two liver tumor lesions with at least one with a diameter of 2 cm or bigger, which is amendable for (super-)selective TATE as the target lesion. Alternatively, patients with one intra-hepatic lesion of 2 cm or bigger and exhapetic lesion(s) are also acceptable.
  5. ECOG score 2 or less
  6. Child-Pugh scores 5-7
  7. Patients should have measurable disease by contrast CT or contrast-enhanced MRI.
  8. All prior chemotherapy must be at least 4 weeks prior to TATE and free from treatment-related toxicity. No gap is needed for prior PD-1 checkpoint inhibitors in NSCLC patients.
  9. Patients have normal organ function: Hemoglobin ≥ 8.5 gm/dL, Platelets ≥ 50,000 /µL, Creatinine ≤ 2 mg/dL, AST and ALT < 10 X upper normal limit of the current institution; bilirubin < 3.0 mg/dL
  10. Patients are able to understand and willing to sign the informed consent.
  11. Men and women of child-bearing age need to commit to using two methods of contraception simultaneously to avoid pregnancy.

Exclusion Criteria:

  1. Patients who have had a liver or any organ transplantation
  2. Patients who take any immune or bone marrow suppressive agents including any systemic corticosteroid that exceed an equivalent of 10 mg prednisone per day within 2 weeks from the study treatment. Inhalation or topical steroids are allowed.
  3. Patients who have received any checkpoint inhibitor, including ipilimumab, nivolumab, pembrolizumab or others.
  4. Patients who have major medical problems such as severe cardiac, pulmonary (COPD requiring constant oxygen), or non-healing ulceration.
  5. Patients with a history of autoimmune disease (e.g., rheumatoid arthritis, Addison's syndrome, multiple sclerosis, uveitis, systemic lupus erythematosus or Wegener's granulomatosis). Patients with vitiligo or alopecia are allowed. Patients with Graves disease or psoriasis not requiring systemic treatment within the past 2 years are allowed.
  6. Patients who have any clinical evidence of hypoxia with O2 saturation less than 92% on room air.
  7. Patients with evidence of significant arterial insufficiency or microangiopathy in any organ due to any reason, which could lead to distal extremity hypoxia, as evidenced by any gangrenous change in distal limbs or requiring resection for this reason.
  8. Patients with major gastrointestinal bleeding in the prior 2 months of enrollment.
  9. Patients who are pregnant or lactating.
  10. Patients with QTc interval > 480 msec or those known to have congenital long QTc syndrome.
  11. Patients who have received live, attenuated vaccine within 28 days prior to the first dose of PD-1 inhibitor.

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): NCT03259867


Locations
Layout table for location information
United States, California
University of California, Irvine
Orange, California, United States, 92868
Sponsors and Collaborators
Teclison Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Nadine Abi-Jaoudeh, MD UC Irvine Medical Center

Layout table for additonal information
Responsible Party: Teclison Ltd.
ClinicalTrials.gov Identifier: NCT03259867     History of Changes
Other Study ID Numbers: LT-004
First Posted: August 24, 2017    Key Record Dates
Last Update Posted: September 11, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Teclison Ltd.:
Hepatocellular carcinoma
Colorectal cancer
Immune checkpoint inhibitor
Gastric cancer
Non-small cell lung cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Hepatocellular
Stomach Neoplasms
Liver Neoplasms
Colorectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Adenocarcinoma
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Stomach Diseases
Intestinal Neoplasms
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Pembrolizumab
Nivolumab
Tirapazamine
Antineoplastic Agents, Immunological
Antineoplastic Agents