bowel cancer colorectal carcinoma
Conditions
Interventions
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Histological or cytological proof of CRC; 2. Disease progression or relapse upon at least one line of treatment for advanced CRC with fluoropyrimidine containing chemotherapy as single agent or in combination (combinations with oxaliplatin, irinotecan, bevacizumab and cetuximab/panitumumab are allowed); 3. Written documentation of activated TGF-* signature-like gene signature, as determined by the validated assay of Agendia; 4. Age * 18 years; 5. Able and willing to give written informed consent; 6. WHO performance status of * 1; 7. LVEF * 55%; 8. Able and willing to undergo blood sampling for PK and PD analysis; 9. Able and willing to undergo tumor biopsies before start, during treatment and at the end of treatment 10. Life expectancy * 3 months allowing adequate follow up of toxicity evaluation and anti-tumor activity; 11. Evaluable disease according to RECIST 1.1 criteria (measurable disease for the phase II part; evaluable disease is sufficient for the phase I part); 12. Minimal acceptable safety laboratory values a. ANC of * 1.5 x 10^9 /L b. Platelet count of * 100 x 10^9 /L c. Hepatic function as defined by serum bilirubin * 1.5 x ULN, ALAT and ASAT * 3.0 x ULN, or ALAT and ASAT * 5 x ULN in patients with liver metastases d. Renal function as defined by serum creatinine *1.5 x ULN e. Creatinine clearance * 50 ml/min (by Cockcroft-Gault formula or MDRD); 13. Negative pregnancy test (urine or serum) for female patients with childbearing potential.
Exclusion criteria
Exclusion criteria: 1. Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment; 2. Known or suspected dihydropirimidine dehydrogenase deficit (Mutant for DPD*2A genotype, 1236 GA genotype, 1679TG genotype and 2846A>T genotype); 3. Symptomatic or untreated leptomeningeal disease; 4. Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enrol. Brain metastasis must be stable with verification by imaging (e.g. brain MRI or CT (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: To determine the recommended phase 2 dose (RP2D) of galunisertib plus capecitabine in patients with chemotherapy resistant activated TGF-* signature-like CRC. Phase II: To determine the anti-tumor activity, as measured by response rate (RR) of galunisertib in combination with capecitabine in patients with chemotherapy resistant activated TGF-* signature-like CRC. | — |
Secondary
| Measure | Time frame |
|---|---|
| - To characterize the safety and tolerability of galunisertib in combination with chemotherapy regimens, as assessed by the incidence and severity of adverse events - To assess anti-tumor activity of galunisertib in combination with chemotherapy, as measured by duration of response, time to response and, progression free survival (phase II only) and overall survival (phase II only) - To determine the pharmacokinetic profile of galunisertib in combination with chemotherapy, as measured by plasma concentrations - To explore genetic determinants of response to galunisertib in combination with chemotherapy, as measured by baseline molecular status of potential predictive markers of tumor response - To explore the potential mechanism of resistance to galunisertib in combination with chemotherapy, as measured by gene alterations/expression profiles (e.g. baseline, relapse) in tumor tissue upon progression | — |
Countries
The Netherlands
Outcome results
None listed