This is a first-in-human Phase 1 clinical trial designed to investigate the safety, tolerability, pharmacokinetics, and biodistribution of [225Ac]-FPI-2059 and [111In]-FPI-2058 in participants with neurotensin receptor 1 (NTSR1)-expressing solid tumours.
Background
Pancreatic cancer is one the leading causes of cancer-related death in Canada. Approximately 40 percent of patients with pancreatic cancer present with locally advanced pancreatic cancer and are not candidate for curative surgery. The optimal management of patients with locally advanced pancreatic cancer remains unknown. Most patients are treated with chemotherapy alone and role of local treatment such as radiation is not well defined. Other conventional ablative therapies such as thermal ablation and cryoablation have limited role in locally advanced pancreatic cancer due to the risk of collateral damage to the adjacent structures. Irreversible electroporation (IRE) is a novel non-thermal ablation technology that does not cause injury to nearby blood vessels, ducts, and bowel and has potential to provide longer disease control and thereby a better overall survival. The current study aims to prospectively validate effectiveness and safety of IRE in real-world patients with locally advanced pancreatic cancer.
Objectives
1) To determine 12-month progression-free survival (PFS) and 24-month overall survival rates of patients with locally advanced pancreatic cancer who are treated with combination chemotherapy and IRE and 2) to compare progression-free and overall survival of patients with locally advanced pancreatic cancer who are treated with combination chemotherapy and IRE versus combination chemotherapy alone.
Design
Prospective multicenter single arm study.
Methods
Based on the assumption of doubling of PFS of patients who are being treated with IRE and chemotherapy versus chemotherapy alone we estimated a sample of n=27 of adult patients with histologically proven non-metastatic locally advanced adenocarcinomas. Eligible patients will be recruited at the two major cancer centers in Saskatchewan. All IRE eligible patients will receive 12 weeks of induction chemotherapy and will undergo repeat imaging studies. If there is no disease progression IRE will be performed. An additional 12 weeks of chemotherapy will be recommended. Patients who are not eligible for IRE due to size criteria will receive chemotherapy at the discretion of treating oncologist till disease progression or till they become eligible for IRE. Quality of life will be assessed every three months or until disease progression.
Significance
Despite progress in the management of most solid organ cancers and better outcomes, little advancement has been made in the treatment of patients with locally advanced pancreatic cancer. Unfortunately, most patients have very limited life expectancy. There is an unmet need for novel approaches in the management of patients with locally advanced pancreatic cancer. IRE in combination with chemotherapy has potential to improve local disease control and thereby improves survival and may prove a valuable tool to add in the multidisciplinary treatment of cancer. The result of this study will be used for the development of a future multicenter national phase III trials.
Determine the doses and schedule appropriate for phase 2 study of sorafenib and vorinostat with concurrent gemcitabine and radiation therapy (RT) as neoadjuvant treatment of pancreatic cancer following chemotherapy. Recommended phase II dose RP2Ds and schedule of sorafenib and vorinostat defined as the doses and schedule that are the same as or less than the maximum tolerated dose (MTD) and schedule.
The application of immunotherapeutic strategies that target the most potent antigen presenting cell, the dendritic cell (DC), are likely to substantially increase the magnitude of the anti-tumor immune response. Although there are issues of activation state and antigen load, mechanisms to increase the number of DCs available to the immune system are among the first steps in development of affective DC based immunotherapeutic strategies. The Central Hypothesis of our study is: Administration of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) to patients with pancreatic adenocarcinoma will result in enhance recruitment of DCs to the sentinel lymph node, into the peripheral blood, and/or tumor site. We propose performing a phase I, dose escalation, clinical trial of systemic and intra-tumoral GM-CSF administration for the treatment of pancreatic adenocarcinoma. This trial will be designed to assess toxicity and immunologic effects, principally dendritic cell recruitment. Patients with resectable pancreatic adenocarcinoma by clinical staging criteria will be eligible for enrollment.
The trial we propose is a phase I clinical trial of the addition of GM-CSF as a biological adjuvant to standard care for patients with potentially resectable pancreatic adenocarcinoma.
Background: Monotherapy with S-1, oral fluoropyrimidine, shows non-inferiority to gemcitabine in overall survival (OS) with good tolerability for advanced pancreatic cancer in Asian patients. It is also shown that nimotuzumab plus gemcitabine could improve OS and progression free survival (PFS) in patients with unresectable pancreatic cancer. However, it is still unknown whether nimotuzumab plus S1 would improve more to OS and PFS than single S-1. Maintenance treatment, as a new treatment pattern, has also been tried in these patients after first line treatment to improve the OS. Thus, this study is designed to compare nimotuzumab plus S1 to placebo plus S1 as maintenance treatment in patients with locally advanced or metastatic pancreatic cancer who has benefited from the first-line treatment of gemcitabine combined with nimotuzumab and S1 (complete response+partial response+stable disease).
Patients and methods: 60 patients will be enrolled,and randomized in a 1:1 ratio to group nimotuzumab plus S1 and group placebo plus S1. nimotuzumab/placebo: 400 mg/w, intravenous infusion, Infusion time ≥ 60 min, d1, once every two weeks. S1: oral, 40 mg (Body surface area1.5 m2), d1-d14, every three weeks for a cycle. Treatment interventions will be stopped under the conditions of disease progression or intolerable toxic reaction or participants ask to quit. The primary endpoint is the time to disease progression since randomization (TTP), secondary points include OS, 3 years overall survival rate (OSR) and safety.
Background:
Cancer in the liver can start in the liver (e.g., primary liver cancer or hepatocellular cancer) or spread to the liver from cancers in other parts of the body (e.g. colon, pancreas, gastric, breast, ovarian, esophageal cancers, cancer with metastases to the liver.) People who have tumors that can be removed by surgery live longer than those whose cancer cannot be removed. Chemotherapy can shrink some tumors in the liver, which also helps people to live longer, and sometimes chemotherapy can shrink tumors enough that they can be removed by surgery. However, most chemotherapy drugs do not work well on tumors in the liver. In this study we are testing a new drug, TKM-080301, given directly into the cancer blood supply in the liver circulation, to see if it will cause tumors to shrink.
Objectives:
– To test the safety and effectiveness of TKM-080301 for cancer in the liver that has not responded to standard treatments.
Eligibility:
– Individuals at least 18 years of age who have inoperable cancer that has started in or spread to the liver.
Design:
* Participants will be screened with a medical history and physical exam. They will also have blood tests, and imaging studies.
* Participants will have a liver angiogram (type of X-ray study) to look at the blood flow in the liver and to place a catheter for delivery of the TKM080301.
* Participants will have a single dose of TKM-080301 given directly into the liver. After the drug has been given, the catheter will be removed. They will have frequent blood tests and keep a diary to record side effects.
* Participants may have two more doses, each dose given 2 weeks apart. {Before each dose, participants will have another angiogram and catheter placement.}They may also have liver biopsies to study the tumors.
* Two weeks after the third treatment (one full course), participants will have a physical exam, blood tests, and imaging studies. If the tumor is shrinking, they may have up to three more courses of the study drug.
* Participants will have follow up visits every 3 months for 2 years after the last course and then every 6 months as required.
This is a subprotocol of Master Protocol DAY101-102 and is a Phase 1b/2, multi-center, open label subprotocol of participants ≥12 years of age, with recurrent or progressive solid tumors with alterations in the key proteins of the MAPK pathway, such as tumors that harbor RAS or RAF alterations.
*Note: Study concluded as Phase 1b only.
The primary objective of this study, sponsored by Travera Inc. in Massachusetts, is to validate whether the mass response biomarker has potential to predict response of patients to specific therapies or therapeutic combinations using isolated tumor cells from various specimen formats including malignant fluids such as pleural effusions and ascites, core needle biopsies, fine needle aspirates, or resections.
Irreversible electroporation (IRE) is a new, minimal-invasive image-guided treatment method for tumors not amenable for surgical resection or thermal ablation, due to vicinity near vital structures such as vessels and bile ducts. With IRE, multiple electrical pulses are applied to tumorous tissue. These pulses alter the existing transmembrane potential of the cell membranes, and create 'nanopores', after which the cell dies through loss of homeostasis.
The purpose of this study is to investigate the safety of percutaneous IRE in the treatment of patients with locally advanced pancreatic carcinoma (LAPC). Other objectives are feasibility and efficacy of IRE based upon symptomatic response and tumor response.
Fourty patients with histologically confirmed locally advanced pancreatic adenocarcinoma (<5cm) will undergo percutaneous irreversible electroporation of the tumor using CT and ultrasound guidance. After IRE, patients will be carefully monitored and any (serious) adverse events are registered. Follow-up will consist of frequent CT scanning, as well as serum CA19.9 tumor marker.
We hypothesize that IRE in the pancreas will induce good symptom palliation and local tumor control, without causing severe complications.
Safety study to determine highest dose of 90Y-hPAM4 can be safety administered
