NCT01608139

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.

Trial Health

10
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Status
withdrawn

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Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 25, 2012

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 30, 2012

Completed
5 months until next milestone

Study Start

First participant enrolled

November 1, 2012

Completed
10 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2022

Completed
Last Updated

October 19, 2012

Status Verified

October 1, 2012

Enrollment Period

10 years

First QC Date

May 25, 2012

Last Update Submit

October 17, 2012

Conditions

Keywords

Advanced CancersAdvanced Solid TumorsCurcuminSorafenibNexavarBay 43-9006VorinostatSAHASuberoylanilide Hydroxamic AcidMSK-390Zolinza

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose (MTD)

    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.

    4 weeks

Study Arms (1)

Curcumin + Sorafenib + Vorinostat

EXPERIMENTAL

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.

Drug: CurcuminDrug: SorafenibDrug: Vorinostat

Interventions

Starting dose: 4 grams by mouth per day. During the first cycle only, Curcumin given on Day 1. Beginning with Cycle 1 Day 5, all agents will be administered continuously.

Curcumin + Sorafenib + Vorinostat

Starting dose: 200 mg by mouth daily. During the first cycle only, Sorafenib given on Day 5. Beginning with Cycle 1 Day 5, all agents will be administered continuously.

Also known as: Nexavar, Bay 43-9006
Curcumin + Sorafenib + Vorinostat

Starting dose: 100 mg by mouth daily. During the first cycle only, Vorinostat given on Day 3. Beginning with Cycle 1 Day 5, all agents will be administered continuously.

Also known as: SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza
Curcumin + Sorafenib + Vorinostat

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Links

MeSH Terms

Interventions

CurcuminSorafenibVorinostat

Intervention Hierarchy (Ancestors)

DiarylheptanoidsHeptanesAlkanesHydrocarbons, AcyclicHydrocarbonsOrganic ChemicalsCatecholsPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicPhenylurea CompoundsUreaAmidesNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-RingAnilidesAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic Acids

Study Officials

  • David S. Hong, MD

    UT MD Anderson Cancer Center

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 25, 2012

First Posted

May 30, 2012

Study Start

November 1, 2012

Primary Completion

November 1, 2022

Last Updated

October 19, 2012

Record last verified: 2012-10