Prospective non randomized, non-comparative, dose escalation, two arms open phase I trial to assess the safety and tolerability of capecitabine given in combination with aflibercept in patients with measurable or evaluable, chemorefractory digestive tumors or breast tumors in terms of the Maximum Tolerated Dose (MTD) and the Dose-Limiting Toxicities (DLTs), To establish the Recommended Phase II Dose (RP2D) of capecitabine in combination with Aflibercept.
Aflibercept has been found to be active with a broad pharmacological index against early and advanced stage disease in a variety of preclinical solid tumor models including sarcomas, and ovarian, prostate, mammary, colon, and gastric carcinomas either as a single agent or in combination with cytotoxic agents. Metronomic chemotherapy, namely administration of continuous low-dose chemotherapy at close, regular intervals, with no prolonged drug-free interruptions, bases its rationale on the fact that virtually all classes of cancer chemotherapeutic drugs are designed to damage DNA or disrupt microtubules of dividing cells. Endothelial cell division takes place during new blood vessel formation, including tumour angiogenesis. Frequent administration of most cytotoxic agents at low doses is thought to increase their putative antiangiogenic activity. This strategy lowers the toxicity and theoretically the risk of emergence of drug-resistant tumour cells compared to classic maximum tolerated dose (MTD)-based chemotherapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
37
escalation dose of capecitabine continuously
Intravenous 6mg/kg every 3 weeks
dose escalation, from 1700 to 2500mg/m2/day 2 weeks out of 3
Institut Jules Bordet
Brussels, Belgium
To determine the maximum tolerated dose and the recommended phase II dose of capecitabine in association with aflibercept
To assess the safety and tolerability of capecitabine given in combination with aflibercept in patients with measurable or evaluable, chemorefractory digestive tumors or breast tumors in terms of the Maximum Tolerated Dose (MTD), the Dose-Limiting Toxicities (DLTs), and to determine the Recommended Phase II Dose (RP2D) of capecitabine in combination with aflibercept.
Time frame: The time point of the first toxicity evaluation would be the end of the first cycle (3 weeks)
The secondary endpoint is preliminary data on efficacy, and this will be evaluated using CT scan or MRI using RECIST (Response Evaluation Criteria in Solid Tumors) v1.1
Time frame: after 2 cycles (6 weeks)
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