A Multi-Center Phase I Study of Intravenous Deforolimus (AP23573, MK-8669) Administered QDX5 Every Other Week in Pediatric Patients With Advanced Solid Tumors (8669-028)(COMPLETED) - Full Text View

Sponsor:	Merck
Collaborators:	H. Lee Moffitt Cancer Center and Research Institute Pediatric Cancer Foundation University of Colorado, Denver All Children's Hospital Memorial Sloan-Kettering Cancer Center
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00704054

Purpose

Ridaforolimus (Deforolimus, AP23573, MK-8669) 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
Solid Tumors	Drug: ridaforolimus	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: AP 23573

U.S. FDA Resources

Further study details as provided by Merck:

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: Duration of trial ] [ 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. Screening at Day 1-18, Cycle 2 Day 1, Cycle 2 Day 15. [ Time Frame: Duration of trial ] [ Designated as safety issue: Yes ]
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: Duration of trial ] [ Designated as safety issue: Yes ]
To assess pharmacogenomic parameters from archival tumor specimens that may correlate with response to ridaforolimus. [ Time Frame: Duration of trial ] [ Designated as safety issue: No ]

Enrollment:	15
Study Start Date:	January 2008
Study Completion Date:	June 2010
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 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. Other Name: AP23573, deforolimus, MK-8669

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

Sponsors and Collaborators

Merck

H. Lee Moffitt Cancer Center and Research Institute

Pediatric Cancer Foundation

University of Colorado, Denver

All Children's Hospital

Memorial Sloan-Kettering Cancer Center

Investigators

Principal Investigator:	Lisa Gore, MD	University of Colorado, Denver
Study Director:	Christopher Turner, MD	Ariad Pharmaceuticals

More Information

Additional Information:

Pediatric Cancer Foundation This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Vice President of Late Stage Development, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00704054 History of Changes
Other Study ID Numbers:	AP23573-07-110, SUN08-01
Study First Received:	June 23, 2008
Last Updated:	July 7, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Merck:

Pediatric
Solid Tumor
CNS Tumor
Lymphoma

Additional relevant MeSH terms:

Neoplasms
Sirolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on February 09, 2012