A Dose-regimen Finding Study to Evaluate Safety, Tolerability, Pharmacokinetics and Activity of Oratecan in Subjects With Advanced Malignancies

NCT02250157 | Completed Phase 1

• 1 other identifier: ORTE-01-14-US
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

This study a nonrandomized, open-label, uncontrolled, single group assignment, safety and activity study in subjects with histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Number of participants with dose limiting toxicities

  2 years

Secondary Outcomes (3)

• Number of patients with adverse events

  2 years

• Area under the plasma concentration versus time curve

  2 years

• Tumor measurements per RECIST 1:1

  2 years

Study Arms (2)

Part 1

EXPERIMENTAL

Part 1 of this study is a "3+3" design to define the MTD of Oratecan in up to 60 evaluable subjects. It will be conducted in 2 parts; 1A will test the oral liquid formulation and 1B will test the oral tablet formulation of irinotecan.

Drug: Oratecan

Part 2

EXPERIMENTAL

Part 2 will enroll an additional 10 subjects at the Part 1 MTD to further characterize the safety, tolerability, pharmacokinetics, and activity of Oratecan at that dose.

Drug: Oratecan

Interventions

Oratecan DRUG

Also known as: Camptosar, HM30181

Part 1; Part 2

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent.
• ≥ 18 years of age.
• Histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria.
• Adequate bone marrow reserve as demonstrated by :
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 10⁹/L.
• Platelet count ≥ 100 x 10⁹/L.
• Hemoglobin ≥ 9 g/L.
• Adequate liver function as demonstrated by:
• Total bilirubin of ≤ 1.5 mg/dL or ≤ 2.0 mg/dL for subjects with liver metastasis.
• Alanine aminotransferase ≤ 3 x ULN or ≤ 5 x ULN if liver metastasis is present.
• Alkaline phosphatase ≤ 3 x ULN or ≤ 5 x ULN if bone metastasis is present
• Adequate renal function as demonstrated by serum creatinine ≤ 1.5 x ULN or 24-hour urine creatinine clearance calculation ≥ 60 mL/min.
• Eastern Cooperative Oncology Group performance status of 0 to 1.
• Life expectancy of at least 3 months.

You may not qualify if:

• Subjects who are homozygous for the UGT1A1\*28 allele
• Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous IPs.
• Received IPs within 14 days or 5 half-lives of the first study dosing day, whichever is longer.
• Are currently receiving other medications intended for the treatment of their malignancy.
• Women who are pregnant or breast feeding.
• Taking a medication known to be clinically significant P-gp inhibitors or inducers within 14 days of treatment with Oratecan.
• Chronically taking an oral medication known to be a P-gp substrate within 7 days of starting treatment with Oratecan.
• Taking a medication known to be a clinically significant cytochrome (CYP) 3A4 strong inhibitor (eg, ketoconazole within 14 days) or strong inducers (eg, rifampin and St. John's Wort within 14 days) of starting treatment with Oratecan. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm
• Require therapeutic use of anticoagulation medications
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, cardiac arrhythmia, chronic pulmonary disease requiring oxygen, known bleeding disorders, or any concomitant illness or social situation that would limit compliance with study requirements.
• Major surgery to the upper gastrointestinal (GI) tract, or have a history of GI disease or other medical condition that, in the opinion of the investigator may interfere with oral drug absorption.
• Allergy or sensitivity to irinotecan or cranberry-grape juice, or any of the irinotecan tablet excipients. .

Sponsors & Collaborators

• Athenex, Inc.: lead

Study Sites (2)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Interventions

Irinotecan; 4-oxo-4H-chromene-2-carboxylic acid (2-(2-(4-(2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl)-phenyl)-2H-tetrazol-5-yl)-4,5-dimethoxyphenyl)amide

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Donal Landers, MD

  Athenex, Inc.

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: September 22, 2014
• First Posted: September 26, 2014
• Study Start: September 5, 2014
• Primary Completion: March 4, 2020
• Study Completion: March 4, 2020
• Last Updated: February 22, 2022

Record last verified: 2022-02

Locations

US (2)