A Dose-Escalation Study of ENMD-2076 Administered Orally to Patients With Advanced Cancer

An Open-Label, Dose-Escalation, Safety, and Pharmacokinetic Study of ENMD-2076 Administered Orally to Patients With Advanced Cancer

A dose-escalation trial designed to assess the safety and tolerability of treatment with ENMD-2076 administered orally over a range of doses in patients with advanced cancer that is refractory to current treatment or for which no curative therapy exists.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: ENMD-2076

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Massachusetts
    • Boston, Massachusetts, United States
      • Dana Farber/Harvard Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have histologic proof of advanced cancer that has progressed after treatment and has no standard therapy that is curative or provides clinical benefit.
• Meet the modified RECIST Criteria or have disease that can be followed for clinical benefit.
• Are greater than or equal to 18 years of age.
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Total bilirubin ≤ ULN
• Creatinine ≤ 1.5 x ULN
• Absolute neutrophil count ≥ 1500 cells/mm3
• Platelets ≥ 100,000/mm3
• Hemoglobin ≥ 9.0 g/dL
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Agree to use effective contraceptive methods prior to study entry, during study participation, and for at least 30 days after the last administration of study medication.
• Have the ability to understand the requirements of the study, provide written informed consent which includes authorization for release of protected health information, abide by the study restrictions, and agree to return for the required assessments.

Exclusion Criteria:

• Women who are pregnant or nursing.
• Have received radiotherapy or chemotherapy less than two weeks prior to first dose of study medication and have not recovered from all acute toxicities from prior treatments.
• Have participated in any clinical trial involving conventional or investigational drugs within 28 days prior to initiation of ENMD-2076 dosing.
• Have active, acute, or chronic clinically significant infections.
• Have uncontrolled severe hypertension or congestive heart failure.
• Have active angina pectoris or recent myocardial infarction (within 6 months).
• Have chronic atrial fibrillation or QTc of greater than 470 msec.
• Have had major surgery within 21 days of starting therapy.
• Have planned surgical treatment of tumor(s)
• Have additional uncontrolled serious medical or psychiatric illness.
• Have any medical condition that would impair the administration of oral agents including significant bowel resection, inflammatory bowel disease or uncontrolled nausea or vomiting.
• Have a 2+ protein by urinalysis or a history of nephrotic syndrome.
• Known central nervous system metastasis.
• Have history of deep vein thrombosis or pulmonary embolus, unless they are receiving therapeutic anticoagulation with warfarin or low-molecular-weight heparin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Dose-escalation	Drug: ENMD-2076; Capsules, daily dosing in 28 day cycles
EXPERIMENTAL: 2; Advanced cancer, excluding patients with colorectal or ovarian cancers	Drug: ENMD-2076; Capsules, daily dosing in 28 day cycles
EXPERIMENTAL: 3; Recurrent or resistant epithelial ovarian cancer	Drug: ENMD-2076; Capsules, daily dosing in 28 day cycles
EXPERIMENTAL: 4; Colorectal cancer patients who have progressed and/or failed on irinotecan- and oxaliplatin-based regimens	Drug: ENMD-2076; Capsules, daily dosing in 28 day cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of ENMD-2076	Throughout study treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma PK	Throughout study treatment
Evidence of benefit (tumor response, clinical benefit, or tumor marker improvement, if appropriate)	Throughout study treatment

Collaborators and Investigators

• Sponsor: CASI pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Diamond JR, Bastos BR, Hansen RJ, Gustafson DL, Eckhardt SG, Kwak EL, Pandya SS, Fletcher GC, Pitts TM, Kulikowski GN, Morrow M, Arnott J, Bray MR, Sidor C, Messersmith W, Shapiro GI. Phase I safety, pharmacokinetic, and pharmacodynamic study of ENMD-2076, a novel angiogenic and Aurora kinase inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2011 Feb 15;17(4):849-60. doi: 10.1158/1078-0432.CCR-10-2144. Epub 2010 Dec 3.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (ACTUAL): December 1, 2010
• Study Completion (ACTUAL): June 1, 2012

Study Registration Dates

• First Submitted: April 11, 2008
• First Submitted That Met QC Criteria: April 11, 2008
• First Posted (ESTIMATE): April 15, 2008

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: February 2, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 2076-CL-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No