Metastatic Biliary Cancers Clinical Trial
Official title:
Modulation of Metabolic Index in Tailoring Treatment of Incurable Metastatic ColoRectal Cancer (CRC) Program 1.
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.
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