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

NCT01159301 | Terminated Phase 1

• 4 other identifiers: NCI-2011-01435CDR0000675600I-1654098272
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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. Entinostat and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Myeloid Leukemia; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

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

  28 days

• Safety as assessed by the NCI CTCAE version 4.0

  Up to 30 days

Secondary Outcomes (3)

• Pharmacokinetic profile of sorafenib tosylate

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

• Pharmacokinetic profile of entinostat

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

• 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

  Up to 30 days

Study Arms (1)

Treatment (entinostat, sorafenib tosylate)

EXPERIMENTAL

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.

Drug: entinostat; Drug: sorafenib tosylate; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

entinostat DRUG

Given orally (PO)

Also known as: HDAC inhibitor SNDX-275, SNDX-275

Treatment (entinostat, sorafenib tosylate)

sorafenib tosylate DRUG

Given PO

Also known as: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN

Treatment (entinostat, sorafenib tosylate)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (entinostat, sorafenib tosylate)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (entinostat, sorafenib tosylate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute; Blast Crisis

Interventions

entinostat; Sorafenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Alex Adjei

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 8, 2010
• First Posted: July 9, 2010
• Study Start: June 1, 2010
• Primary Completion: September 1, 2013
• Last Updated: September 19, 2013

Record last verified: 2013-09

Locations

US (1)