Clinical Trial Information

Clinical Trial #1

A Multi-Center Phase I Study of AP23573 in Pediatric Patients With Advanced Solid Tumors

Deforolimus is an mTOR inhibitor shown to have promising activity in adults with a variety of solid malignancies, particularly the sarcomas. To date, no studies to evaluate appropriate dosing or to obtain pharmacokinetic data in pediatric patients have been conducted. Sarcomas are the second most common solid malignancies in children and young adults, and for those patients with recurrent or refractory disease, new therapies are needed. This initial evaluation of deforolimus will help define appropriate dosing and toxicity evaluations, as well as establish the first pharmacokinetic and biologic correlative data in pediatric patients treated with deforolimus.

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:

• To establish the DLT and the MTD of deforolimus administered daily x 5 every 14 days in pediatric patients with recurrent/refractory solid tumors, including lymphoma and tumors of the central nervous system. [ Time Frame: 2010 ] [ Designated as safety issue: Yes ]

• To determine the pharmacokinetic and pharmacodynamic properties of deforolimus in pediatric patients with recurrent/refractory solid tumors, including tumors of the central nervous system. [ Time Frame: 2010 ] [ Designated as safety issue: No ]
  
• To evaluate the safety and efficacy data of deforolimus when administered at the MTD or recommended phase II dose and schedule in an expanded cohort of patients when administered daily x 5 every 14 days [ Time Frame: 2010 ] [ Designated as safety issue: Yes ]
  
• To assess pharmacogenomic parameters that may correlate with response to deforolimus [ Time Frame: 2010 ] [ Designated as safety issue: No ]

Criteria

Inclusion Criteria:

• Male or female age 1 to <18 years at the time of study entry for the dose escalation portion of the study
• Histologic diagnosis of a malignant lymphoma or solid tumor, including tumors of the central nervous system that has progressed in the opinion of the investigator despite standard therapy or for which no effective standard therapy is known
• Patients may have measurable or non-measurable disease as defined by RECIST
• Patients with brainstem glioma or intrinsic pontine glioma do not need biopsy proof of the diagnosis, but must have documentation at their local institution that there is agreement among the attending oncologist and/or neuro-oncologist, radiologist, and neurosurgeon/pediatric neurosurgeon that the diagnostic imaging studies are consistent with a diagnosis of brainstem or intrinsic pontine glioma
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, surgery or radiotherapy prior to entering this study
• Performance Status: EGOG 0-2 for patients age 16 and older; Karnofsky >40% for patients >10 years of age; Lansky Play Scale >40 for children < 10 years of age
• Life expectancy greater than or equal to 12 weeks
• There is no limit to the number of prior treatment regimens provided that performance status, organ function, and life expectancy meet the study criteria
• No persistent toxicities from previous therapies > Grade 2 by NCI CTCAE version 3. For patients with CNS tumors ONLY, if baseline neurotoxicity due to primary tumor involvement or post-operative complications, Grade 3 neurotoxicity is allowed if stable
• Normal organ and marrow function
• For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment
• Patients who enter this study and their sexual partners who are of childbearing potential must agree to use an effective form of contraception

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within three (3) weeks (or six weeks for nitrosoureas or mitomycin C) prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients receiving any other investigational agents or using any investigational devices
• Patients with leukemia
• Patients who have previously received deforolimus or other rapamycin analogs
• History of allergic reactions (in opinion of the investigator) attributed to compounds of similar chemical or biologic composition to deforolimus and its excipients used in administration
• Uncontrolled intercurrent illness
• Pregnant women are excluded from this study because the teratogenic or abortifacient effects of deforolimus are not known at this time
• Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, known HIV-positive patients are excluded from the study because of possible pharmacokinetic interactions with deforolimus
• Autologous or allogeneic stem cell transplant <3 months prior to enrollment; any evidence of on-going graft versus host disease (GVHD), or GVHD requiring immunosuppressive therapy. Patients who have had prior stem cell transplant regimens must be discussed with and approved by the principal investigator prior to registration