A Study to Assess the Effect of Food on the Bioavailability of the IGF-1R Inhibitor AXL1717 in Patients With Advanced Malignant Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Axelar AB
ClinicalTrials.gov Identifier:
NCT01725555
First received: October 26, 2012
Last updated: April 4, 2014
Last verified: April 2014
  Purpose

This is a prospective, randomized, open-label, Phase I, crossover study to assess the effect of food on the bioavailability of AXL1717 including patients with advanced malignant tumors


Condition Intervention Phase
Solid Tumors
Hematological Malignancies
Drug: Fasted treatment: AXL1717
Drug: Fed treatment: AXL1717
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Randomized, Open-label, Phase I, Crossover Study to Assess the Effect of Food on the Bioavailability of AXL1717, in Patients With Advanced Malignant Tumors

Resource links provided by NLM:


Further study details as provided by Axelar AB:

Primary Outcome Measures:
  • Single dose AXL1717 serum pharmacokinetic profile under fasting versus fed condition in each patient [ Time Frame: several samples within 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety of AXL1717 through adverse event reporting [ Time Frame: Up to 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]

Enrollment: 13
Study Start Date: October 2012
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fasted treatment Drug: Fasted treatment: AXL1717 Drug: Fed treatment: AXL1717
Experimental: Fed treatment Drug: Fasted treatment: AXL1717 Drug: Fed treatment: AXL1717

Detailed Description:

This is a randomized, crossover, open label, phase I study to assess the effect of food on the bioavailability of AXL1717 in advanced cancer patients.

A single, oral dose of AXL1717 is to be administered to patients on each of two occasions that are 7-day apart, in random order: after an overnight fast (fasted treatment) and with a high-fat or moderate-fat breakfast (fed treatment).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be informed of the nature of the study and have provided written informed consent
  2. At least 18 years of age
  3. Histologically confirmed diagnosis of advanced solid or hematological malignancy not amenable to standard treatment.
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 after optimization of analgesics
  5. Life expectancy ≥ 3 months
  6. Hematology values: blood leukocyte count ≥ 3.0 x 109/L, blood absolute neutrophil count ≥ 1.5 x 109/L, blood platelet count ≥ 100 x109/L, hemoglobin ≥ 100 g/L (transfusions are allowed)
  7. Clinical chemistry values: plasma total bilirubin level ≤ 1.5 times the upper limit of the "normal" range (ULN; i.e. reference), plasma AST or ALT ≤ 1.5 x ULN (≤5 times if liver metastases have been documented) and plasma creatinine ≤ 1.5 x ULN
  8. 12-lead ECG with normal tracings; or changes that are not clinically significant and do not require medical intervention

Exclusion Criteria:

  1. Ongoing infection or other major recent or ongoing disease that, according to the Investigator, poses an unacceptable risk to the patient
  2. Known primary or secondary central nervous system malignancy. (Patients with symptoms suggestive of possible CNS metastasis such as headache, dizziness or focal neurological deficits should undergo CT or MRI of the brain to rule out CNS metastasis. Patients who do not have CNS symptoms do not need a CT or MRI of the brain.)
  3. Grade 3 or higher constipation within the past 28 days or grade 2 constipation within the past 14 days before randomization. (Patients with grade 2 constipation within the past 14 days could be re-screened if constipation decreases to ≤ grade 1 with optimal management of constipation.)
  4. Impairment of gastrointestinal (GI) function, GI cancer or GI disease that may significantly alter the absorption of AXL1717
  5. Coexisting uncontrolled medical condition, including active cardiac disease (such as unstable angina, myocardial infarction within 6 months, or New York Heart Association Class III/IV congestive heart failure), or significant dementia
  6. Hepatic impairment as indicated by abnormalities of transaminases and/or alkaline phosphatase (AST and/or ALT > 1.5 × upper limit of normal concomitant with alkaline phosphatase > 2.5 × upper limit of normal, ≤5 times if liver metastases have been documented)
  7. Major surgical procedure within 4 weeks prior to randomization
  8. Use of potent inhibitors of CYP2C9 (e.g. Fluconazole) from 3 weeks prior to first administration of investigational product
  9. Women of child bearing potential (WOCBP) who do not consent to using acceptable methods of contraception (i.e. two of the following - oral contraception, barrier contraception, intrauterine device). For purposes of this study, WOCBP include any female who has experienced menarche, who has not undergone tubal ligation, and who is not postmenopausal. Post menopause is defined as: amenorrhea ≥ 12 consecutive months without another cause.
  10. Women who are breast-feeding or have a positive pregnancy test at screening
  11. Current participation in any other investigational clinical trial or any administration of an investigational agent within 4 weeks of study drug administration or 10 half-lives of the investigational agent, whichever is longer. Patients with unresolved investigational treatment-related AEs may not participate.
  12. Known or suspected hypersensitivity to AXL1717
  13. Lack of suitability for participation in the trial, for any reason, as judged by the Investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01725555

Locations
Sweden
KFUE
Uppsala, Sweden
Sponsors and Collaborators
Axelar AB
Investigators
Principal Investigator: Simon Ekman, M.D., Ph.D. Uppsala University Hospital, Sweden
  More Information

No publications provided

Responsible Party: Axelar AB
ClinicalTrials.gov Identifier: NCT01725555     History of Changes
Other Study ID Numbers: AXL010
Study First Received: October 26, 2012
Last Updated: April 4, 2014
Health Authority: Sweden: Medical Products Agency
Sweden: Regional Ethical Review Board
Sweden: Swedish Data Inspection Board

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 23, 2014