Study of CH5132799 Administered Orally in Patients With Advanced Solid Tumors

Solid Tumors Clinical Trial

Official title:

Phase I, Open-label, Multi-center, Dose-escalation Study to Evaluate Safety, Pharmacokinetics and Activity of CH5132799 Administered Orally as a Monotherapy in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01222546
• Other study ID #: PA-001EU
• Status: Completed
• Phase: Phase 1
• First received: October 14, 2010
• Last updated: June 20, 2014
• Start date: August 2010
• Est. completion date: December 2012

Study information

• Verified date: June 2014
• Source: Chugai Pharma Europe Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multi-center, dose-escalation Phase I study to evaluate safety, pharmacokinetics and activity of CH5132799 administered orally as a single agent in patients with advanced solid tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: December 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Provision of signed written informed consent.

2. Histologically or cytologically confirmed diagnosis of advanced solid tumor.

3. Age = 18 years.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

5. Life expectancy of = 12 weeks.

6. Disease measurability:

Patients must have a measurable - as per Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1 - and/or evaluable disease.

7. Paraffin-embedded archival tumor tissue available. Fresh biopsies will be required if no paraffin embedded tumor tissues available.

8. Adequate bone marrow function.

9. Adequate cardiac function: Patient should have Left Ventricular Ejection Fraction (LVEF) of = 50% as determined by echocardiography (ECHO) or Multi Gated Acquisition (MUGA) scans.

10. Adequate liver function.

11. Adequate renal function.

12. Adequate adrenal function assessed by baseline cortisol of > 200 nmol/L

13. Ability to comply with protocol requirements.

14. Female patients must be postmenopausal (12 months of amenorrhea), surgically sterile or they must agree to use a physical method of contraception. Male patients who have been sterilized must agree to use a barrier method of contraception. Male subjects must also commit to use a barrier method of contraception until at least 3 months after the end of study treatment.

15. Female patients of child-bearing potential must have a negative serum pregnancy test within the seven days prior to the first study drug administration.

Exclusion Criteria:

1. History of allergic reactions attributed to components of the formulated product.

2. Inability to swallow oral medications or impaired gastrointestinal absorption due to active inflammatory bowel disease.

3. Known Central Nervous System (CNS) metastases or leptomeningeal metastases will be eligible only if it could be radiologically demonstrated that there is no CNS disease progression during the 3 months prior to the study

4. Known active or uncontrolled pulmonary dysfunction.

5. Uncontrolled hypertension

6. Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy for bone pain), or immunotherapy within 28 days of first receipt of study drug (within 6 weeks for nitrosoureas and mitomycin C). Hormone therapy within 14 days of first receipt of study drug, with exception of prostate cancer if indicated.

7. Prior toxicities from chemotherapy or radiotherapy which have not regressed to Grade = 1 severity - National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0).

8. Type 1 or 2 diabetes mellitus requiring regular medication and/or a fasting plasma glucose (FPG) = 120 mg/dL (or 6.6 mmol/dL) at screening.

9. Increased QTc interval (QTc > 450 ms for male; > 460 ms for female).

10. History of heart failure, refractory hypokalemia to adequate supplementation, family history of long QT syndrome or other risk factors for "Torsades de Pointes", and/or the use of concomitant medications that prolong the QT/QTc interval.

11. Prior corticosteroid therapy within 14 days of first receipt of study drug.

12. Treatment with any investigational agent within 28 days of first receipt of study drug.

13. Acute or chronic infection. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding or any other medical condition that, in the opinion of the investigator, contraindicates the use of an investigational drug, or will impose excessive risk to the patient.

14. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.

15. History of clinically significant bowel disease including abdominal fistula, gastro-intestinal perforation, and diverticulitis.

16. Major surgery within 28 days of first receipt of study drug.

17. Pregnant or lactating women

18. Altered mental status or psychiatric disorder that, in the opinion of the investigator, would preclude a valid patient informed consent.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• CH5132799

Locations

Country	Name	City	State
United Kingdom	Investigator Sites	London	Leeds

Sponsors (1)

Lead Sponsor	Collaborator
Chugai Pharma Europe Ltd.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of dose limiting toxicities		Upon completion of the study	Yes
Primary	Preliminary anti-tumour activity		Upon completion of the study	No
Secondary	To determine the pharmacokinetics of CH5132799		Upon completion of the study	No
Secondary	To characterise the pharmacodynamic effect of CH5132799 in surrogate tissues		Upon completion of the study	No