ADVL1312 - A Phase I/II Study of MK-1775 in Combination with Oral Irinotecan

ADVL1312: A Phase I/II Study of MK-1775 in Combination with Oral Irinotecan in Children, Adolescents, and Young Adults with Relapsed or Refractory Solid Tumors

Diseases

Patients must have relapsed or refractory solid tumors, including CNS tumors. 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

MK-1775 is a Wee1 inhibitor, developed to block this tyrosine kinase that is activated in response to DNA damage and plays a role in chemo-resistance. Patients will receive MK-1775 orally in combination with oral irinotecan on days 1-5 of a 21-day cycle. Additionally, patients will take cefixime, or equivalent antibiotic, for irinotecan-related diarrheal prophylaxis. Therapy may continue for up to 18 cycles in the absense of disease progression or unacceptable toxicity.

Eligibility Criteria

  • Patients must be between 12 months and 21 years of age.

  • 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.

  • Patients previously treated with irinotecan are eligible for this study.

  • Must have adequate organ function as evidenced by laboratory criteria.
  • Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled. Must not have received enzyme inducing anticonvulsants for at least 14 days prior to enrollment.
  • Must be able to swallow 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 strong or moderate inhibitors and/or inducers of CYP3A4 or sensitive CYP3A4 substrates and CYP3A4 substrates with a narrow therapeutic range.
  • Must not have an uncontrolled infection.
  • Must not have received a prior solid organ transplantation.
  • Must not have a history of allergic reaction to irinotecan, cephalosporins, or a severe penicillin allergy.

Contact

For the current status and more detailed eligibility criteria of these clinical studies & protocols, referring physicians and families may call the Developmental Therapeutics Program directly at (832) 824-4266 at any time. Kate Mazur,RN, MSN, CPNP, a pediatric nurse practitioner for the Developmental Therapeutics Program, will answer any questions or concerns you may have. You may need to leave a voice mail, and she will return your call as soon as possible. She may also be reached by email at kamazur@txch.org.