Biomarker Development for Response Prediction by DNA Mutational Analysis (CPCT-01)

P.O. Witteveen

Status: Terminated

Conditions: Neoplasm Metastasis

Treatments: Procedure: Pharmacokinetics; Procedure: Midazolam clearance test; Procedure: Biopsy; Procedure: Blood samples

Study type: Observational

Funder types: Other

Identifiers

NCT01855061

NL35198.041.11

Details and patient eligibility

About

The purpose of this study is to determine whether it is possible to predict response to chemotherapy in patients with metastatic cancer who are treated with irinotecan by determining the mutational profile of the tumor.

Enrollment: 79 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with a metastatic solid tumor who have failed at least one line of palliative chemotherapy and are irinotecan naïve.

2. Patients who are, as per local protocol, eligible for palliative treatment with (standard of care) irinotecan.

3. Measurable metastatic lesion(s), according to RECIST 1.1 criteria.

4. Radiological measurable metastatic lesion(s) of which a histological biopsy can safely be obtained:

   1. Patients with safely accessible metastases.

   2. Patients not known with bleeding disorders (such as hemophilia) or bleeding complications from biopsies, dental procedures or surgeries.

   3. Patients not using any anti-coagulant medication at the time of biopsy: all aspirin derivatives, NSAID's, coumarines, platelet function inhibitors, heparins (including LMWHs) and oral factor Xa inhibitors are not allowed, unless medication can either be safely stopped or counteracted.

   4. Adequate coagulation status on the day of biopsy as measured by:

      • PTT < 1.5 x ULN
      • APTT < 1.5 x ULN
      • Platelet count 100 x 10*9 / L or higher
      • PT-INR < 1.6
      • HB > 6

   5. Biopsies should be performed at least four weeks after last bevacizumab administration.

5. Patients age 18 years or up, willing and able to comply with the protocol as judged by the investigator with a signed informed consent.

Exclusion criteria

Patients not meeting all of the above inclusion criteria.

Trial design

79 participants in 1 patient group

Irinotecan

Description:

Patients will be subjected to a their metastatic solid tumor. Radiological response will be evaluated after each 2 cycles: 1. percentage change in radiological volume of the "index lesion" (radiological measurable lesion that underwent biopsy) after the first two cycles of irinotecan; 2. radiological response according to RECIST 1.1 after each 2 cycles. Patients are intended to receive irinotecan until progressive disease or unacceptable toxicity. Patients will be subjected to another biopsy of the index lesion at definitive discontinuation of irinotecan. Patients will also be subjected to blood draws for determining patient's genetic background variation. Side studies include: * pharmacogenetics * pharmacokinetics of SN-38 * carboxylesterase activity in the index lesion * midazolam clearance test (only in Rotterdam patients)

Treatment:

Procedure: Blood samples

Procedure: Biopsy

Procedure: Midazolam clearance test

Procedure: Pharmacokinetics