Phase I-II Trial of Erlotinib in Higher Risk Myelodysplastic Syndrome
This is a phase I-II multicenter, open label, sequential cohort dose escalation study of
erlotinib designed to assess the safety and efficacy of a daily administration of erlotinib
in high risk MDS patients.
Five patients per cohort will be enrolled into sequential cohorts receiving increasing
dosages of erlotinib. The first cohort of 5 patients will start with a dosage of 100 mg
erlotinib daily. Response will be determined after 12 weeks of treatment (or earlier upon
major hematologic improvement, whichever event occurs first). At the completion of each
cohort, defined as the fifth subject completing the week 12 visit, the safety review panel
will be responsible for making the decision as to whether the next cohort will begin, an
intermediate dose cohort will be added, or if additional subjects will be enrolled into an
earlier dose cohort.
Upon agreement of the safety review panel, the second cohort of patients will receive 150 mg
of erlotinib daily, and - upon agreement of the safety review panel - the third cohort of
five patients will be enrolled to receive 300 mg of erlotinib daily.
Since it is to be expected that the therapeutically required dosage of erlotinib is higher
than the dosage for which a patient was initially enrolled (i.e. patient enrolled in the
first cohort receiving 100 mg daily), dosage of erlotinib should be increased (for the same
patient) to the next higher level, if no response is documented after 12 weeks of continuous
treatment and no grade III or IV toxicity is documented. In contrast, responders will
continue their treatment with the same dosage of erlotinib until grade III or IV toxicity
arises or treatment loses efficacy (as defined by relapse/progression of the disease).
Consequently, this study plans to enrol 15 patients in 3 cohorts of 5 patients. Once the
dose limiting toxicity has been defined, additional confirmatory subjects (20) will be
enrolled into the appropriate lower dose as recommended by the safety review panel.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary objective is to estimate the overall response rate (CR, PR, mCR The primary objective is to estimate the overall response rate (CR, PR, mCR and HI according to the IWG 2000 and 2006 criteria) in patients treated with erlotinib.
After 12 weeks treatment
Sylvain Thepot, MD
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)