Pilot Study of Curcumin, Vorinostat, and Sorafenib in Patients With Advanced Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Withdrawn
- Sponsor
- M.D. Anderson Cancer Center
- Primary Endpoint
- Maximum Tolerated Dose (MTD)
Study Overview
Brief Summary
The goal of this clinical research study is to learn the highest tolerable dose of the combination of curcumin, vorinostat, and sorafenib that can be given to patients with advanced solid cancer. The safety of this drug combination will also be studied.
Detailed Description
The Study Drugs:
Curcumin is the active ingredient in the spice, turmeric. It is a natural anti-inflammatory compound and has shown anti-tumor activity in the laboratory and in clinical trials.
Vorinostat is designed to cause chemical changes in different kinds of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die.
Sorafenib is designed to block the ability of important proteins to activate in cancer cells. These proteins, when active, are in part responsible for the abnormal growth and behavior of cancer cells. Blocking their activity may slow the growth of the cancer cells or cause the cancer cells to die.
Study Groups:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients must have an advanced solid tumor that has either failed one or more prior therapies or where there is no established standard of care therapy.
- •Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 2 or better (0-2).
- •Patients must have normal organ and marrow function as defined below: Absolute neutrophil count (ANC) > 1,500/uL; Platelets > 100,000/uL; Total bilirubin within normal limits (patients with Gilbert's syndrome must have total bilirubin < 3.0 mg/dL) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x the institutional upper limit of normal (ULN); Creatinine </= 1.5 x ULN; Hemoglobin >/= 9.0 gm/dL; prothrombin time (PT)/ partial thromboplastin time (PTT) within normal limits
- •Patients must be able to understand and be willing to sign an IRB-approved written informed consent document.
- •Women of child-bearing potential (women who are not postmenopausal for at least one year or are not surgically sterile) and men must agree to use adequate contraception (e.g. barrier method) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
- •Patients must be 18 years of age or older since the safety and dosages of these study drugs has not been demonstrated in the pediatric population. However, patients who are 13 years old or older and have more than 50 kg of body weight will be eligible after consultation with their pediatric attending.
Exclusion Criteria
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association (NYHA) Class III or IV), unstable angina pectoris, symptomatic cardiac arrhythmia, active bleeding, active thrombosis, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Inadequately controlled hypertension (defined as systolic blood pressure > 140 and/or diastolic blood pressure > 90 mmHg on antihypertensive medications), any prior history of hypertensive crisis or hypertensive encephalopathy, and history of myocardial infarction or unstable angina within 6 months prior to study enrollment.
- •History of stroke or transient ischemic attack within 6 months prior to study enrollment and significant vascular disease (e.g., aortic aneurysm, aortic dissection) and symptomatic peripheral vascular disease.
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study. Minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.
- •History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or GI bleeding within 6 months prior to study enrollment; or serious, non-healing wound, ulcer, or bone fracture. Patients who have had a history of acute diverticulitis, GI obstruction, abdominal carcinomatosis, or peptic ulcer disease (known risks for bowel perforation) confirmed by endoscopy within the past 6 months, will also be excluded.
- •Patients on therapeutic warfarin with history of deep vein thrombosis and/or pulmonary embolism.
- •History of allergic reactions to the study drugs or their analogs.
- •Patients that have had any treatment specific for tumor control within 3 weeks of study drug treatment or: a. within 2 weeks if cytotoxic agents were given weekly b. within 6 weeks for nitrosoureas or mitomycin C c. within 4 half-lives for targeted agents with half lives and pharmacodynamic effects lasting less than 5 days (that includes, but is not limited to, erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents) d. failed to recover from toxic effects of any therapy prior to study entry
- •Urine for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate </= 1g of protein in 24 hours to be eligible).
- •Patients with insulin dependent diabetes or poorly controlled type 2 diabetes.
- •Inability to swallow oral medication.
- •Pregnant or breastfeeding women.
- •Concurrent enrollment on another research study.
Arms & Interventions
Curcumin + Sorafenib + Vorinostat
Participant assigned to a dose level of the study drug combination based on when joined this study. Up to 9 dose levels of the study drug combination will be tested. Three (3) to 6 participants will be enrolled at each dose level of the study drug combination. During first cycle only, Curcumin initiated on Day 1, Vorinostat on Day 3 and Sorafenib on Day 5. Beginning with Cycle 1 Day 5, all agents administered continuously. Cycle of therapy is 28 days.
Starting dose of Curcumin: 4 grams by mouth per day on Day 1. Starting dose of Sorafenib: 200 mg by mouth daily beginning on Day 5. Starting dose of Vorinostat: 100 mg by mouth daily beginning on Day 3.
Intervention: Curcumin (Drug)
Curcumin + Sorafenib + Vorinostat
Participant assigned to a dose level of the study drug combination based on when joined this study. Up to 9 dose levels of the study drug combination will be tested. Three (3) to 6 participants will be enrolled at each dose level of the study drug combination. During first cycle only, Curcumin initiated on Day 1, Vorinostat on Day 3 and Sorafenib on Day 5. Beginning with Cycle 1 Day 5, all agents administered continuously. Cycle of therapy is 28 days.
Starting dose of Curcumin: 4 grams by mouth per day on Day 1. Starting dose of Sorafenib: 200 mg by mouth daily beginning on Day 5. Starting dose of Vorinostat: 100 mg by mouth daily beginning on Day 3.
Intervention: Sorafenib (Drug)
Curcumin + Sorafenib + Vorinostat
Participant assigned to a dose level of the study drug combination based on when joined this study. Up to 9 dose levels of the study drug combination will be tested. Three (3) to 6 participants will be enrolled at each dose level of the study drug combination. During first cycle only, Curcumin initiated on Day 1, Vorinostat on Day 3 and Sorafenib on Day 5. Beginning with Cycle 1 Day 5, all agents administered continuously. Cycle of therapy is 28 days.
Starting dose of Curcumin: 4 grams by mouth per day on Day 1. Starting dose of Sorafenib: 200 mg by mouth daily beginning on Day 5. Starting dose of Vorinostat: 100 mg by mouth daily beginning on Day 3.
Intervention: Vorinostat (Drug)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD)
Time Frame: 4 weeks
Maximum tolerated dose (MTD) defined by dose limiting toxicities (DLTs) that occur in the first cycle. Hematological DLT defined as platelets less than 25,000/uL or bleeding associated with platelets less than 50,000/uL, ANC less than 500/uL for more than 7 days, neutropenic fever, hemoglobin less than 6.5 g/dL, or more than 14 days of delay in initiation of subsequent treatment because of inadequate hematological parameters. Nonhematological toxicities graded by using NCI CTCAE v4.0 toxicity criteria.
Secondary Outcomes
No secondary outcomes reported