ADVL1212 - A Phase I Study of Crizotinib in Combination with Conventional Chemotherapy

ADVL1212: A Phase I Study of Crizotinib in Combination with Conventional Chemotherapy for Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma

Diseases

Patients must have relapsed or refractory solid tumors or anaplastic large cell lymphoma (ALCL), excluding patients with primary or metastatic CNS tumors or patients with primary cutaneous ALCL. Patient’s current disease state must be one for which there are no known curative treatment options or therapies proven to prolong survival with an acceptable quality of life.

Description

Crizotinib is a small molecule inhibitor of the c-Met/HGFR and ALK receptor tyrosine kinase, which are both implicated in the development of multiple malignancies. Crizotinib will be administered orally twice daily in combination with topotecan and cyclophosphamide daily x 5 every 3 weeks. Additionally, patients will receive myeloid growth factor starting on day 6 of each cycle. Therapy may continue for up to 24 months in the absense of disease progression or unacceptable toxicity.

Eligibility Criteria

• Patients must be between 12 months and 21 years of age and have a BSA greater than or equal to 1.07 m2 at the time of study enrollment.
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy and have the appropriate wash-out period from most recent cancer directed therapy, with the exception of ALCL patients who relapse while receiving standard maintenance chemotherapy who will not require any wash out period.
• Patients must not have received prior therapy with crizotinib.
• Must have adequate organ function as evidenced by laboratory criteria and EKG.
• Must be able to swallow intact capsules.
• Patients receiving corticosteroids must be on a stable or decreasing dose for at least 7 days prior to enrollment.
• Must not be receiving drugs that are potent inhibitors or inducers of CYP3A4 or CYP3A4 substrates with a narrow therapeutic indices.
• Must not have an uncontrolled infection.
• Must not have received a prior solid organ transplantation.
• Must not have a primary or metastatic CNS tumor at the time of study enrollment. A prior history of metastatic CNS tumor is allowed as long as there is no evidence of CNS disease at time of enrollment.