Phase I Study of Ipilimumab (Anti-CTLA-4) in Children and Adolescents With Treatment-Resistant Cancer
|ClinicalTrials.gov Identifier: NCT01445379|
Recruitment Status : Completed
First Posted : October 3, 2011
Last Update Posted : May 18, 2018
|First Submitted Date ICMJE||September 30, 2011|
|First Posted Date ICMJE||October 3, 2011|
|Last Update Posted Date||May 18, 2018|
|Study Start Date ICMJE||October 1, 2007|
|Actual Primary Completion Date||April 18, 2014 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
||To determine the tolerance and toxicity profile of ipilimumab in patients less than 21 years of age with refractory tumors at a range of doses up to, but not exceeding the highest dose tolerated in adults.|
|Change History||Complete list of historical versions of study NCT01445379 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
||Efficacy, immunomodulatory activity.|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Phase I Study of Ipilimumab (Anti-CTLA-4) in Children and Adolescents With Treatment-Resistant Cancer|
|Official Title ICMJE||A Phase I Study of Ipilimumab (Anti-CTLA-4) in Children, Adolescents, and Young Adults With Treatment Refractory 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.
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.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Ipilimumab
Dose Level Escalation: 1mg/kg, 3mg/kg, 5mg/kg, 10mg/kg
|Study Arms||Experimental: 1
Ipilumumab (DSE) given on day 1 of 21 day cycle for 4 cycles, from cycle 5+ ipilumumab will be given ~every 12wks
Intervention: Drug: Ipilimumab
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date||November 13, 2015|
|Actual Primary Completion Date||April 18, 2014 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
AGE: Patients must be greater than or equal to 1 years and less than or equal to 21 years of age.
DIAGNOSIS: Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing s sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilm s tumor, Hodgkin's or non-Hodgkin's lymphoma. Patients with melanoma are eligible. Patients with a previous history of CNS metastases are eligible if the metastases have been treated with surgery and/or radiotherapy, are clinically stable as evidenced by no requirements for corticosteroids, the patient has no evolving neurologic deficits and no progression in residual brain abnormalities without specific therapy over 4 weeks.
MEASURABLE/EVALUABLE DISEASE: Patients must have measurable or evaluable tumors.
PERFORMANCE STATUS: Patients greater than 10 years old must have a Karnofsky Score of greater than or equal to 50 and children less than 10 years old must have a Lansky score of greater than 50. Patients who are unable to walk because of paralysis or weakness, but who are up in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.
HEMATOLOGIC FUNCTION: Patients must have adequate bone marrow function, defined as a peripheral absolute granulocyte count of greater than or equal to 1000/microL, hemoglobin greater than or equal to 8 gm/dl, and a platelet count greater than or equal to 50,000/microL (may be corrected with transfusions).
HEPATIC FUNCTION: Aspartate transaminase (AST) and alanine transaminase (ALT), less than or equal to 2.5-fold the upper limit of normal (ULN). Normal total bilirubin.
RENAL FUNCTION: Patients must have normal age-adjusted serum creatinine (see table below) OR a creatinine clearance greater than or equal to 70 mL/min/1.73 m(2).
MAXIMUM SERUM CREATININE LEVEL FOR AGE:
-A patient with viral hepatitis (HBV, HCV) or human immunodeficiency virus (HIV) will be excluded from trial to limit confounding variables in the assessment of the potential hepatic toxicity of ipilimumab and uncertain impact of ipilimumab administration on viral replication. Serology will not be required unless infection is clinically suspected. A positive hepatitis B titer does not exclude a patient if immunization has been performed and if there is no history of disease.
INFORMED CONSENT: All patients or their legal guardians (if the patient is less than 18 years old) must sign a document of informed consent (Pediatric Oncology Branch, NCI screening protocol for NIH patients) prior to performing studies to determine patient eligibility. After confirmation of eligibility, all patients or their legal guardians must voluntarily sign the IRB approved protocol specific informed consent to document their understanding of the investigational nature, the risks of this study and their willingness to receive the therapy and undergo the research studies involved including pharmacokinetic studies. The consent must be signed before any protocol related studies are performed (This does not include routine laboratory tests or imaging studies required to establish eligibility). When appropriate, pediatric patients will be included in all discussions in order to obtain verbal assent.
DURABLE POWER OF ATTORNEY (DPA): Patients who are greater than or equal to 18 years of age will be offered the opportunity to assign a DPA so that another person can make decisions about their medical care if they become incapacitated or cognitively impaired.
BIRTH CONTROL: Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control which includes abstinence, while they are being treated on this study and for 60 days following the last dose. Females of childbearing potential must have a negative pregnancy test within 14 days prior to initiation of study therapy and prior to each additional dose of ipilimumab.
sarcoid granuloma, myasthenia gravis, polymyositis, and Guillain-Barre syndrome.
|Ages||3 Years to 21 Years (Child, Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01445379|
|Other Study ID Numbers ICMJE||080007
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Cancer Institute (NCI)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||November 13, 2015|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP