Phase I Study of Ipilimumab (Anti-CTLA-4) in Children and Adolescents With Treatment-Resistant Cancer
This study will examine the safety and efficacy of ipilimumab-an experimental cancer treatment drug used to boost immune response-in children, adolescents, and young adults. Ipilimumab may allow immune cells to react to and destroy abnormal cells in the body, and has been tested in adults for a variety of cancers and has shown responses in some research studies. Because ipilimumab has not been tested in children, adolescents, or young adults, it is considered an experimental drug. The purposes of this research study are to determine the highest safe dose of ipilimumab for children, adolescents, and young adults with solid tumor cancers; examine its effectiveness and possible side effects; and better understand how the body and the immune system process it over time.
Candidates must be between 2 and 21 years of age and must have solid malignant tumors that have been resistant to standard therapy. Volunteers will be screened with a medical history, a clinical examination, and computerized scans such as magnetic resonance imaging (MRI). Participants must have completed their last dose of chemotherapy, radiation, chemotherapy, or antibody or investigational therapy at least four weeks prior to enrollment.
During the study, participants will receive an intravenous dose of ipilimumab once every three weeks. The infusion of ipilimumab will last 90 minutes, and the participant s vital signs will be monitored while the medicine is infusing and several times in the first 24 hours after the first dose (requiring a hospital stay during that time). If the participant is able to tolerate the first dose of ipilimumab, further doses (called cycles ) may be received on an outpatient basis. Blood and urine tests will be given on a regular basis during these cycles. After four cycles, participants whose tumors do not grow and who do not have unacceptable side effects will continue to receive ipilimumab every three months to maintain the current condition, until researchers conclude the study.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Ipilimumab (Anti-CTLA-4) in Children, Adolescents, and Young Adults With Treatment Refractory Cancer|
- To determine the tolerance and toxicity profile [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Pharmacokinetics [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Evaluate immunomodulatory activity. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Quantify antitumor effects [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||October 2007|
|Study Completion Date:||April 2014|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Ipilumumab (DSE) given on day 1 of 21 day cycle for 4 cycles, from cycle 5+ ipilumumab will be given ~every 12wks
Dose Level Escalation: 1mg/kg, 3mg/kg, 5mg/kg, 10mg/kg
Solid tumors represent approximately one fourth of cancer diagnoses in children. Despite intensive regimens, patients with metastatic or recurrent solid tumors have unsatisfactory survival rates. Therefore new therapies are needed to improve outcomes.
Accumulating preclinical and clinical evidence supports the use of biologic approaches to heighten antitumor immunity in order to improve the effectiveness of immune based therapy. Both directly activating immune based therapies such as cytokines and tumor vaccines as well as therapies which disrupt negative counterregulatory signals such as those mediated by CTLA-4:B7 may enhance existent antitumor immune responses.
Antibodies directed against CTLA-4 potently augment immune responses in animal models and anti-CTLA-4 antibodies have demonstrated antitumor effects in a variety of preclinical tumor models.
Phase I and phase II studies using ipilimumab have been performed in adults with a variety of tumor types. Clinical responses have been observed in renal cell carcinoma, melanoma, and prostate cancer. No trials have yet been performed to evaluate ipilimumab in children with malignancy.
To determine the tolerance and toxicity profile of ipilimumab at a range of doses up to, but not exceeding, the highest dose tolerated in adults, in patients less than or equal to 21 years of age with refractory solid tumors.
To assess the pharmacokinetics of ipilimumab administered intravenously in patients less than or equal to 21 years of age with advanced and/or refractory solid tumors.
Patients must be 1-21 years of age at the time of enrollment with solid malignant tumors refractory to standard therapy.
A Phase I dose finding study with 4 planned dose levels.
Three patients will be enrolled at each dose level with an expanded cohort of 12 at the highest or maximum torlerated dose with intent to include 6 patients < 12 years.
Re-induction with 4 infusions of ipilimumab at the assigned dose followed by another maintenance phase is possible for subjects who have progressed during maintenance therapy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01445379
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|United States, Massachusetts|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10021|
|Principal Investigator:||Melinda S Merchant, M.D.||National Cancer Institute (NCI)|