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A Multi-Center Phase I Study of Intravenous Deforolimus (AP23573, MK-8669) Administered QDX5 Every Other Week in Pediatric Patients With Advanced Solid Tumors
This study is currently recruiting participants.
Verified by Ariad Pharmaceuticals, September 2009
First Received: June 23, 2008   Last Updated: September 14, 2009   History of Changes
Sponsor: Ariad Pharmaceuticals
Collaborators: H. Lee Moffitt Cancer Center and Research Institute
Pediatric Cancer Foundation
University of Colorado at Denver and Health Sciences Center
All Children's Hospital
Memorial Sloan-Kettering Cancer Center
Information provided by: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00704054
  Purpose

Ridaforolimus 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 Ridaforolimus will help define appropriate dosing and toxicity evaluations, as well as establish the first pharmacokinetic and biologic correlative data in pediatric patients treated with ridaforolimus.


Condition Intervention Phase
Neoplasm
Lymphoma
Drug: ridaforolimus
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment, Safety Study
Official Title: A Multi-Center Phase I Study of Intravenous Deforolimus (AP23573, MK-8669) Administered QDX5 Every Other Week in Pediatric Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Ariad Pharmaceuticals:

Primary Outcome Measures:
  • To establish the DLT and the MTD of ridaforolimus 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 ]

Secondary Outcome Measures:
  • To determine the pharmacokinetic and pharmacodynamic properties of ridaforolimus 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 ridaforolimus 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 ridaforolimus [ Time Frame: 2010 ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: June 2008
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Ridaforolimus is given as an IV infusion over 30 minutes on days 1-5 and 15-19 of each 28 day cycle. For children less than 10 kg body weight, dosing will be adjusted.
Drug: ridaforolimus
Ridaforolimus is given as an IV infusion over 30 minutes on days 1-5 and 15-19 of each 28 day cycle. For children less than 10 kg body weight, dosing will be adjusted.

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00704054

Contacts
Contact: Michael Nieder, MD 727-767-6856 niederm@allkids.org

Locations
United States, Arizona
Phoenix Children's Hospital Recruiting
Phoenix, Arizona, United States, 85016
Contact: Dr. Jessica Boklan, M.D.     602-546-0920     jboklan@phoenixchildrens.com    
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Dr. Richard Jove, M.D.     626-301-8179     rjove@coh.org    
United States, Colorado
The Children's Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Dr. Lia Gore, MD     720-777-4159     lia.gore@UCHSC.edu    
United States, Florida
All Children's Hospital Recruiting
St. Petersburg, Florida, United States, 33701
Contact: Dr. Michael Nieder, MD     727-767-6856     NiederM@allkids.org    
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Dr. Amy Smith, M.D.     352-392-8724     smithaa@peds.ufl.edu    
Nemours Children's Clinics Recruiting
Jacksonville, Florida, United States, 32207
Contact: Dr. Scott Bradfield, M.D.     904-390-3652     sbradfie@nemours.org    
United States, Georgia
Children's Healthcare of Atlanta at Egleston Recruiting
Atlanta, Georgia, United States, 30322
Contact: Dr. Howard Katzenstein, MD     404-785-0906     howard.katzenstein@choa.org    
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Dr. Tanya M Trippett, M.D.     212-639-8267     trippet1@mskcc.org    
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Dr. Cynthia Herzog, M.D.     713-745-0157     cherzog@mdanderson.org    
Canada, Alberta
Southern Alberta Children's Cancer Program Recruiting
Calgary, Alberta, Canada, T2N 4N2
Contact: Dr. Aru Narendran, M.D.     403-521-3787     anarendr@ucalgary.ca    
Sponsors and Collaborators
Ariad Pharmaceuticals
H. Lee Moffitt Cancer Center and Research Institute
Pediatric Cancer Foundation
University of Colorado at Denver and Health Sciences Center
All Children's Hospital
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Lisa Gore, MD University of Colorado at Denver and Health Sciences Center
Study Director: Christopher Turner, MD Ariad Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: ARIAD Pharmaceuticals, Inc. ( Christopher Turner, MD )
Study ID Numbers: AP23573-07-110, SUN08-01
Study First Received: June 23, 2008
Last Updated: September 14, 2009
ClinicalTrials.gov Identifier: NCT00704054     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Ariad Pharmaceuticals:
Pediatric
Solid Tumor
CNS Tumor
Lymphoma

Additional relevant MeSH terms:
Lymphatic Diseases
Neoplasms
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Lymphoproliferative Disorders
Lymphoma

ClinicalTrials.gov processed this record on November 25, 2009