Cytochrom p450 3A4 and 1A2 Phenotyping for the Individualization of Treatment With Sunitinib or Erlotinib in Cancer Patients

NCT01402089 | Completed Phase 4 DMC

• 1 other identifier: SG 327/10
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

It is well known that substantial interindividual variability of CYP3A4/1A2-phenotype activity is an important contributor to individual differences in the sensitivity to the frequently used tyrosine kinase inhibitors sunitinib and erlotinib. This study tests the potential for CYP-phenotyping to predict individual pharmacology and derive dosing algorithms for more tailored treatment of these drugs.

Conditions

Non Small-cell Lung Cancer; Renal-cell Cancer; Gastrointestinal Stroma Tumor

Keywords

phenotyping; cytochrome p450; erlotinib; sunitinib; lung cancer; renal-cell cancer; gastrointestinal stromal tumor

Outcome Measures

Primary Outcomes (1)

• Steady-state partial area-under the plasma concentration-time curve over 24 hours (AUC24h) of sunitinib and erlotinib and CYP3A4/1A2-phenotype activity as defined in the protocol

  Sunitinib or erlotinib area under the concentration-time curve during 24 hours at steady-state conditions, compared with the CYP3A4 or CYP1A2 phenotype activity as assessed by the two probe drugs midazolam (CYP3A4) and/or caffeine (CYP1A2)

  2 weeks

Secondary Outcomes (2)

• Sunitinib and Erlotinib-associated toxicity according to the CTC criteria (v.3.0)

  12 weeks (end of study)

• Concentrations of Sunitinib, Erlotinib and probe drugs (Midazolam, Caffeine) in whole blood, sampled from patient's dried blood spots (DBS)

  12 weeks (end of study)

Interventions

Sunitinib DRUG

Patients with renal-cell cancer or GIST are receiving conventional treatment with sunitinib (50mg/day for 4 out of 6 weeks)

Also known as: Sutent

Erlotinib DRUG

Patients with non small-cell lung cancer receive conventional treatment with erlotinib 150mg/day.

Also known as: Tarceva

Midazolam DRUG

For phenotyping of CYP3A4, all patients receive one-time midazolam 2mg as a drinking solution at the start of study treatment.

Also known as: Midazolam drinking solution

Caffeine DRUG

For phenotyping of CYP1A2, patients with non small-cell lung cancer receive additionally one-time caffeine 100mg as a tablet.

Also known as: Coffeinum N 0.2g

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed renal-cell cancer or gastrointestinal stromal tumor (for sunitinib) or non small-cell lung cancer (for erlotinib)
• Both early or advanced tumor stage
• Indication for the therapeutic use of either sunitinib or erlotinib
• Written informed consent and willing to undergo PK-sampling
• Patients \> 18 years of age
• ECOG performance status or ≤2
• Adequate laboratory parameters:
• i. Serum creatinine and serum bilirubin ≤ 1.5 X ULN ii. Serum ALT and AST ≤ 2.5 X ULN (or ≤ 5 in case of liver metastases) iii. Serum calcium ≤ 11,6 mg/dl (2.9 mmol/L)

You may not qualify if:

• Previous treatment with sunitinib or erlotinib
• Known hypersensitivity to trial drug or any compounds of the drug
• Concurrent radiotherapy
• Concurrent systemic anticancer treatment with the exception of bisphosphonates and bevacizumab in patients with non small-cell lung cancer

Sponsors & Collaborators

• Markus Joerger: lead
• University of Basel: collaborator

Study Sites (1)

Cantonal Hospital St.Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Links

• Institute research homepage

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Gastrointestinal Stromal Tumors; Lung Neoplasms

Interventions

Sunitinib; Erlotinib Hydrochloride; Midazolam; Caffeine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinazolines; Benzodiazepines; Benzazepines; Xanthines; Alkaloids; Purinones; Purines

Study Officials

• Markus Joerger, MD PhD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD-PhD-ClinPharm

Study Record Dates

• First Submitted: July 20, 2011
• First Posted: July 26, 2011
• Study Start: January 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: November 1, 2015
• Last Updated: February 2, 2016

Record last verified: 2016-01

Locations

CH (1)