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Adult Acute Basophilic LeukemiaPhase 1NCT01159301

Entinostat and Sorafenib Tosylate in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory or Relapsed Acute Myeloid Leukemia

A Phase 1 study testing entinostat, sorafenib tosylate and pharmacological study in people with Adult Acute Basophilic Leukemia and Adult Acute Eosinophilic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial is studying the side effects and the best dose of entinostat when given together with sorafenib tosylate in treating patients with advanced or metastatic solid tumors or refractory or relapsed acute myeloid leukemia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
entinostat, sorafenib tosylate and pharmacological study
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited States
Study dates
Jun 2010to Sep 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Must meet 1 of the following criteria:
  • Histologically or cytologically confirmed solid tumors (dose-escalation only)
  • Locally advanced, inoperable, or metastatic disease
  • Evaluable or measurable disease
  • Diagnosis of acute myeloid leukemia (AML) for which no other standard therapy, including stem cell transplantation, is expected to result in meaningful clinical response (expansion cohort only)
  • Refractory or relapsed disease
Show all 66Show fewer
  • Chronic myelogenous leukemia in blast crisis allowed
  • No acute promyelocytic leukemia with t(15;17)
  • Must consent to have fresh tumor, bone marrow aspirate, and biopsy obtained
  • No untreated, symptomatic, or unstable brain metastases
  • No active CNS involvement for patients with AML
  • ECOG performance status 0-1
  • ANC ≥ 1,500/mm³ (dose-escalation only)
  • Platelet count ≥ 100,000/mm³ (dose-escalation only)
  • Hemoglobin ≥ 10 g/dL (dose-escalation only)
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT and AST ≤ 3 times ULN (≤ 5 times ULN for liver metastasis)
  • Creatinine clearance ≥ 40 mL/min
  • Albumin > 3.0 g/dL
  • Plasma phosphorus > lower limit of normal (with supplementation)
  • INR ≤ 1.5
  • APTT ≤ 1.5 times ULN (if not on anticoagulants)
  • Able to swallow oral medications
  • ≥ 16 years old (expanded cohort patients recruited at the University of Colorado site)
  • Must have tolerated prior sorafenib tosylate (dose: 400 mg twice daily), if applicable
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-barrier contraception during the study and for 90 days after completion of study therapy
  • No history of cardiac disease, including any of the following:
  • NYHA class II-IV congestive heart failure
  • Active coronary artery disease
  • Prior diagnosis of bradycardia or other cardiac arrhythmia defined as ≥ grade 2 or uncontrolled hypertension
  • Myocardial infarction (MI) within the past 6 months
  • Persistent tachycardia
  • LVEF < 40% by MUGA
  • Second- or third-degree heart block
  • QTc > 490 msec
  • ST-T wave changes consistent with acute MI or acute ischemia
  • No clinically active serious infections defined as ≥ grade 2
  • No substance abuse, medical, psychological, or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation or evaluation of the study results
  • No condition that is unstable or that could jeopardize the safety of the patient and his/her study compliance
  • No known HIV infection
  • No significant gastrointestinal disorder that, in the opinion of the Investigator, could interfere with the absorption of entinostat and/or sorafenib tosylate including any of the following:
  • Significant, uncontrolled inflammatory bowel disease
  • Abdominal fistula or gastrointestinal perforation within the past 6 months
  • Extensive small bowel resection
  • Requiring tube feeding or parenteral hydration and/or nutrition
  • No concurrent immunosuppressive therapies, including high-dose systemic corticosteroids (> 0.5 mg/kg/day prednisone or equivalent) unless used intermittently or as a tapered course for ≤ 4 weeks
  • Concurrent hydroxyurea and/or anagrelide allowed
  • Concurrent warfarin allowed provided the dose has been stable for the past 2 months and INR has been between 2 and 3
  • More than 4 weeks since prior chemotherapy, immunotherapy, or investigational agents (=< 2 weeks for leukemia patients in expansion cohort)
  • More than 2 weeks since prior palliative radiotherapy
  • More than 4 weeks since major surgery
  • More than 2 weeks since minor surgery (e.g., talc pleurodesis, excisional biopsy, etc.)
  • Concurrent hormonal therapies (e.g., LHRH antagonists, megestrol, octreotide, calcitonin, etc.) allowed
  • No concurrent strong CYP3A4 inducers or inhibitors, including, but not limited to, any of the following:
  • Valproic acid
  • Rifampin
  • Phenobarbital
  • Phenytoin
  • Carbamazepine
  • Ketoconazole
  • Erythromycin
  • Grapefruit
  • No other concurrent anticancer therapy including chemotherapy, radiotherapy (including palliative), or immunotherapy (except hydroxyurea in leukemia patients during course 1)
  • No other concurrent investigational agents

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: A Phase I Study of Sorafenib in Combination With the Histone Deacetylase Inhibitor, Entinostat in Patients With Advanced Cancers

This phase I trial is studying the side effects and the best dose of entinostat when given together with sorafenib tosylate in treating patients with advanced or metastatic solid tumors or refractory or relapsed acute myeloid leukemia. Entinostat and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum-tolerated dose of entinostat in combination with sorafenib tosylate in patients with advanced, inoperable, or metastatic solid tumors.

II. To determine the safety and tolerability of this regimen in these patients.

SECONDARY OBJECTIVES:

  1. To determine the pharmacokinetic profile of this regimen in patients with refractory/relapsed acute myeloid leukemia (AML).

II. To assess the preliminary anti-tumor activity of this regimen in patients with advanced, inoperable, or metastatic solid tumors or refractory/relapsed AML.

III. To evaluate histone deacetylase (HDAC) inhibition of histone acetylation in leukemia blast cells.

TERTIARY OBJECTIVES (EXPLORATORY):

  1. To evaluate the expression of downstream markers of drug activity such as p38, MCL-1, FLT-3, and VEGFR-2 in leukemia blast cells.

II. To evaluate SNDX-induced expression of p21^WAF1/CIP1 in leukemia blast cells.

OUTLINE: This is a multicenter, dose-escalation study of entinostat.

Patients receive oral entinostat once daily on days 1 and 15 and oral sorafenib tosylate twice daily on days 1-28 (days 15-28 only of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients in the expansion cohort undergo blood, bone marrow aspiration, or biopsy for pharmacokinetic studies and biomarker analysis.

After completion of study therapy, patients are followed up for up to 24 months.

Being tested
entinostat, sorafenib tosylate, pharmacological study, laboratory biomarker analysis
Medical subject headings
Leukemia, Basophilic, Acute, Leukemia, Eosinophilic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • entinostatDrug

    Also called HDAC inhibitor SNDX-275, SNDX-275

    Given orally (PO)

  • sorafenib tosylateDrug

    Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar

    Given PO

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01159301
Study groupRoleWhat they receive
Treatment (entinostat, sorafenib tosylate)ExperimentalPatients receive oral entinostat once daily on days 1 and 15 and oral sorafenib tosylate twice daily on days 1-28 (days 15-28 only of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: entinostat; Drug: sorafenib tosylate; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum-tolerated dose as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: 28 days

  2. Safety as assessed by the NCI CTCAE version 4.0

    Measured: Up to 30 days

Secondary outcomes (3)

  1. Pharmacokinetic profile of sorafenib tosylate

    Measured: At baseline, and at days 15, 16, and 28 of course 1, and day 1 of course 2

  2. Pharmacokinetic profile of entinostat

    Measured: At baseline and at days 1, 8, 15, 16, and 22

  3. Objective response rate (ORR) based on the best overall response recorded for each patients or according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    For ORR the 95% confidence interval will be estimated. The 95% confidence interval for percent of patients in each RECIST response category (i.e., CR, PR, SD, and PD) and disease control rate will also be estimated.

    Measured: Up to 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jul 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionSep 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01159301
Sponsor's protocol ID
NCI-2011-01435
Other IDs
NCI-2011-01435, CDR0000675600, I-165409, 8272
Status last verified
Sep 2013
First submitted
8 Jul 2010
Last updated
19 Sep 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing entinostat, sorafenib tosylate and pharmacological study in people with Adult Acute Basophilic Leukemia and Adult Acute Eosinophilic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 66 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum-tolerated dose as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01159301.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2013.

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