Clinical trial NCT02192346: α-TEA in Advanced Cancer
Official title: Phase I Study of Alpha-tocopheryloxyacetic Acid (α-TEA) in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Carcinoma
Metastatic Sarcoma
Metastatic Lymphoma
Keywords: metastatic
refractory
progressive
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
First posted: 2014-07-16
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this study is to find the highest dose of α-TEA that can be given to patients safely, to identify potential side effects of α-TEA, and to measure the amount of α-TEA in patients' blood.

Additional goals of this study are to monitor the effect on tumors, to check for specific immune cells circulating in the blood, and to see if there are certain features of tumors that make it possible to predict the response to α-TEA.

Detailed description: This is a dose-escalation study in which doses ranging from 2.4 mg/kg to 26.8 mg/kg of α-TEA will be tested.

The main clinical objectives of this phase I two-stage dose-escalation trial will be to characterize α-TEA related toxicity, determine the maximum tolerated dose, and pharmacokinetics of α-TEA in humans. Tumor response and exploratory immunological monitoring will also be performed. Specifically, we will determine the frequency of circulating peripheral T cell subset populations including CD4+, CD8+ T cells and their activation status (central memory, effector cells) and regulatory T cells (CD4/CD25/Foxp3). Exploratory monitoring to assess tumor apoptosis and serum cytokine levels will also be performed to gain additional insight on the influence of α-TEA on the immune response and tumor. An assessment of the immunoscore in patients with tumor amenable to biopsy will also provide hypothesis-generating data on the influence of α-TEA on the tumor microenvironment.

Eligibility criteria: Inclusion Criteria:

* Patients with measurable or evaluable metastatic carcinoma, sarcoma or lymphoma who have malignancy refractory or progressed after therapy and for whom no other standard (non-experimental) therapy exists or who have declined available standard therapy, with potential to induce cure, remission or enhanced survival. Either histologic or cytologic diagnosis is acceptable of the primary cancer, or clinical evidence of metastasis.
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
* Age 18 years or above.
* Laboratory values (performed within 28 days prior to enrollment) within protocol specified range.
* Confirmed radiographic and/or serum marker showing cancer progression after at least one systemic therapy for metastatic disease.
* Ability to give informed consent and comply with the protocol. Patients with a history of psychiatric illness must be judged able to understand the investigational nature of the study and the risks associated with the therapy.
* No active bleeding.
* No coagulopathy (INR \<1.5, PT \<16 seconds, PTT \< 38 seconds) at baseline.
* Anticipated lifespan greater than 12 weeks.
* Ability to swallow capsules
* Women of childbearing potential must have a negative pregnancy test and must avoid becoming pregnant while on α-TEA and for 4 weeks after the last dose of α-TEA. Men must avoid fathering a child while on α-TEA and for 4 weeks after the last dose of α-TEA.

Exclusion Criteria:

* Active serious infection that could affect treatment.
* Coagulopathy or need for anti-coagulation therapy.
* Malabsorbtion state such as ulcerative colitis, previous surgical resection of \> 20% of intestine or stomach.
* History of or active atrial fibrilliationfibrillation or supraventricular tachycardia
* Cardiac ejection fraction less than the lower limit of normal on echocardiography
* Right atrial enlargement on echocardiography
* Active cardiac ischemia. Patients with a history of ischemia ameliorated with stent placement or coronary artery bypass grafting and who have no evidence of ischemia by exercise or physiological stress testing are eligible.
* History of or active congestive heart failure
* Patients with tumor that has invaded vagal nerve, carotid bodies, mediastinal structures, pericardium or myocardium.
* Abnormal thyroid function, or euthyroid, but are on medication for thyroid disorders
* Need for chronic high dose maintenance oral steroids. Stable treatment with prednisone ≤ 10 mg daily (or a biologically-equivalent dose of another steroid) is allowed. Patients who require brief courses of steroids to manage allergic reaction to intravenous contrast used in radiographic studies are eligible. Patients requiring steroids for management of CNS metastatic disease are not eligible.
* Surgery or severe trauma within 4 weeks of study entry (minimally invasive procedures acceptable).
* Active brain metastatic disease. Patients with brain metastases who have been treated with surgery, gamma-knife radiosurgery or radiation and no radiographic progression for at least 4 weeks and off steroids are eligible.
* Any medical or psychiatric condition that in the opinion of the PI would preclude compliance with study procedures.
* Vitamin E supplements
* QTc greater than 450 msec at baseline (calculated using Bazett's formula), sick-sinus syndrome or other active cardiac disease.

Primary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: 28 Days
Secondary outcomes:
measure: Number of Adverse Events Possibly Caused by α-TEA
timeFrame: 28 days
measure: Blood serum levels of α-TEA
timeFrame: 28 days
Other outcomes:
measure: Change in Tumor burden from baseline to 28 days
timeFrame: 28 Days
measure: Change in Activity and Proliferation of Circulating T cell Sub-Populations
timeFrame: 28 days
measure: Change in the Number of Tumor-Infiltrating T cells from Baseline to 35 days
timeFrame: 35 days
Locations:
city: Clackamas
country: United States
facility: Providence Oncology & Hematology Care Clinic- Southeast
state: Oregon
city: Newberg
country: United States
facility: Providence Oncology & Hematoloty Care Clinic- Newberg
state: Oregon
city: Oregon City
country: United States
facility: Providence Oncology & Hematology Care Clinic- Willamette Falls
state: Oregon
city: Portland
country: United States
facility: Providence Oncology & Hematology Care Clinic- Eastside
state: Oregon
city: Portland
country: United States
facility: Providence Oncology & Hematology Care Clinic- Westside
state: Oregon
Study officials:
affiliation: Providence Cancer Center, Earle A. Chiles Reserach Institute at the Robert W. Franz Cancer Center
name: Brendan Curti, MD
role: PRINCIPAL_INVESTIGATOR
References: