Clinical Study of Vorinostat in Combination With Etoposide in Pediatric Patients < 21 Years at Diagnosis With Refractory Solid Tumors
Study Details
Study Description
Brief Summary
The purpose of this study is to find out how safe and effective treatment with a new combination of drugs, vorinostat and etoposide, is in treating cancer. The medication etoposide is a standard medication used in the treatment of cancer in children. Vorinostat is an experimental drug which targets a protein(s) that control the way cancer cells grow and divide. Vorinostat is approved by the FDA in adults with certain cancers but not approved yet in children.
There are two parts to this study. In the first part of this study, the phase I portion, a safe dose of the combination, vorinostat and etoposide. The goal of second part of this study, the phase II portion, is to see how effective the combination of vorinostat and etoposide is in treating cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Vorinostat and Etoposide This is a multi-center, open label, phase I/II trial of escalating doses of vorinostat in combination with etoposide. |
Drug: Vorinostat and Etoposide
Patients will be assessed in 3-week cycles. Escalating doses of vorinostat will be administered orally on a daily x 4 schedule in combination with a fixed dose of etoposide. Etoposide will be administered intravenously daily x 3 days. Cohorts of 3-6 patients will be treated with vorinostat and etoposide. In the phase II component, patients will be treated at the RP2D established in the Phase I component of the study, which was found to be 270 mg/m2/dose of Vorinostat and 100 mg/m2/dose of Etoposide.
|
Outcome Measures
Primary Outcome Measures
- To Establish the Dose Limiting Toxicity (DLT) [Patients will be assessed in 3-week cycles.]
of the novel combination vorinostat and etoposide in pediatric patients with refractory solid tumors including tumors of the central nervous system. The Toxicity will be evaluated according to NCI CTCAE Version 4.0.
- To Establish the Maximum Tolerated Dose (MTD) [1 year]
of the novel combination vorinostat and etoposide in pediatric patients with refractory solid tumors including tumors of the central nervous system.
- To Establish the Efficacy (CR (Complete Response) + PR (Partial Response) Rate) [1 year]
of the novel combination vorinostat and etoposide in pediatric patients with relapsed/refractory sarcoma. Evaluation for response will be determined by Revised RECIST guideline
Secondary Outcome Measures
- To Evaluate the Efficacy (CR (Complete Response) + PR (Partial Response) Rate) [1 year]
of the novel combination vorinostat and etoposide in pediatric patients enrolled in the phase I component of the study. Evaluation for response will be determined by Revised RECIST guideline.
- To Evaluate the Biologic Effects Using Histone Acetylation, Gene Expression Profiling, and Histone Phosphorylation Profiling. [2 years]
of the novel combination of vorinostat and etoposide in pediatric patients with refractory solid tumors including central nervous system tumors
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Phase I Component: Histologic confirmation of relapsed/refractory solid tumors, including tumors of the central nervous system that have failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. Patients with diffuse pontine glioma are not required to have histologic confirmation of disease, and are eligible with radiologic confirmation. Phase II Component: the population will be restricted to relapsed/refractory sarcomas
-
Patient must be between 4-21 years of age at the time of study enrollment. Efforts will be made to enroll patients <13 years of age so that adequate information about the biologic effects of this agent in younger patients can be obtained.
-
Patient must have Karnofsky > or = to 60% for patients >10 years of age; Lansky Play Scale > or = to to 60 for children < or = to 10 years of age
-
Patient must have a life expectancy of > 8 weeks.
-
There is no limit to the number of prior treatment regimens provided that performance status and life expectancy meet the criteria above.
-
Absolute neutrophil count (ANC) ≥ 1000 / mcL
-
Platelets ≥100,000 / mcL (transfusion not permitted)
-
Hemoglobin ≥ 9 g/dL qualifications (transfusion permitted)
-
Coagulation Prothrombin Time or INR ≤ 1.5x upper limit of normal (ULN)
-
Serum creatinine ≤ 1.5x upper limit of normal (ULN) OR calculated creatinine clearance ≥ 60 mL/min for patients with creatinine levels > 1.5x institutional ULN. or calculated creatinine clearance Creatinine clearance should be calculated per institutional standard.
-
Serum total bilirubin ≤ 1.5 x ULN Patient's who don't meet this criteria must have a Direct bilirubin ≤ 1.5 x ULN
-
AST (SGOT) and ALT (SGPT) Alkaline Phosphatase (liver fraction)
≤ 2.5 x ULN. If AST or ALT is > 2.5 x ULN, then the liver fraction of Alkaline Phosphatase should be ≤ 2.5 x ULN
-
Phase I component: Patients may have measurable or non-measurable disease. Phase II component: Patients may only have measurable disease.
-
Patient must have no persistent toxicities from prior therapy > or = to Grade 2 with the exception of hematologic indices (i.e. hemoglobin, WBC, ANC, ALC).
-
For females of childbearing potential, a negative serum pregnancy test must be documented within 72 hours of receiving the first dose of vorinostat.
-
Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent.
-
Female patients of childbearing potential must be willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study, starting with visit 1.
-
Male patients must agree to use an adequate method of contraception for the duration of the study.
-
Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
-
Myelosuppressive chemotherapy: At least 2 weeks must have elapsed since the administration of previous therapy. Six weeks must have elapsed since administration of nitrosoureas or mitomycin C. Seven days must have elapsed since the administration of G-CSF and/or GM-CSF.
-
Biologic agents: At least 14 days must have elapsed since the completion of therapy with a biologic agent such as a monoclonal antibody. Seven days must have elapsed since the last dose of retinoids.
-
Radiation therapy (XRT): > or = to 2 weeks must have elapsed for local XRT (small port); > or = to 6 months must have elapsed if prior radiation to > or = to 50% of the pelvis or if other substantial bone marrow irradiation, including total body irradiation.
-
Patient must be able to swallow capsules.
-
Patient must have an available archival/pre-treatment block or fresh tumor biopsy for molecular profiling to be performed.
Exclusion Criteria:
-
A patient meeting any of the following criteria is not eligible to participate in this study:
-
Patients currently participating or has participated in a study with an investigational compound or device within 4 weeks of initial dosing with study drugs.
-
Patients with a prior history of treatment with HDAC inhibitors ( e.g. SNDX-275/entinostat, LAQ-824, LBH589, PXD-101/belinostat, etc). Patients who have received Valproic acid will be excluded from this study.
-
Patients with non CNS primary tumors who have known brain metastases or symptomatic CNS disease (e.g. cranial nerve abnormalities) without cytologic abnormality in the CSF should be excluded from this clinical trial because of their poor prognosis and known propensity for the development of progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with metastatic CNS tumors will not be excluded from enrollment on this study in the phase I component only.
-
Patients who have undergone prior autologous stem cell transplantation or allogeneic transplantation.
-
Uncontrolled intercurrent illness or circumstances that could limit compliance with the study requirements including, but not limited to: ongoing or active bacterial or fungal infection, acute or chronic graft versus host disease, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations.
-
Patients who are pregnant or breastfeeding, or expecting to conceive within the projected duration of the study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, lactating patients will be excluded from this study.
-
Patients known to be Human Immunodeficiency Virus (HIV)-positive.
-
Patients with known hypersensitivity to the components of the study drugs or their analogs.
-
Patients with symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible.
-
Patients who are at the time of signing informed consent, a regular user of any illicit drugs, substance abuser or who have a recent history of drug or alcohol abuse.
-
Patients with a known history of Hepatitis B or C.
-
Patients who have a history of gastrointestinal surgery or other procedures that might in the opinion of the investigator, interfere with the absorption or swallowing of the study drug.
-
Patients who are unable to take or tolerate oral medications on a continuous basis.
-
Patients with a history of a prior malignancy who have undergone potentially curative therapy with no evidence of that disease for five years or patients, who are deemed low risk for recurrence by his/her treating physician are permitted to enroll.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Phoenix Children'S Hospital | Phoenix | Arizona | United States | 85016 |
| 2 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
| 3 | Arnold Palmer Hospital for Children/MD Anderson Cancer Center Orlando | Orlando | Florida | United States | 32806 |
| 4 | All Children's Hospital | Saint Petersburg | Florida | United States | 33701 |
| 5 | John Hopkins Medical Center | Baltimore | Maryland | United States | 21287 |
| 6 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 7 | Children's Mercy Hospital & Clinics | Kansas City | Missouri | United States | 64108 |
| 8 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 9 | Pennsylvania State University College of Medicine | Hershey | Pennsylvania | United States | 17110 |
| 10 | Md Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 11 | Alberta Children'S Hospital | Calgary | Alberta | Canada | T2N 1N4 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
- Merck Sharp & Dohme LLC
- Phoenix Children's Hospital
- Milton S. Hershey Medical Center
- Johns Hopkins University
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Children's Hospital Colorado
- University of Florida
- Alberta Children's Hospital
- M.D. Anderson Cancer Center
- Dana-Farber Cancer Institute
- Children's Mercy Hospital & Clinics
- Johns Hopkins All Children's Hospital
- Arnold Palmer Hospital for Children
Investigators
- Principal Investigator: Tanya Trippett, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 10-096
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Phase II |
|---|---|---|---|---|---|
| Arm/Group Description | 100 mg/m2 Etoposide, 125 mg/m2 Vorinostat + Data Migration | 100 mg/m2 Etoposide, 160 mg/m2 Vorinostat + Data Migration | 100 mg/m2 Etoposide, 210 mg/m2 Vorinostat + Data Migration | 100 mg/m2 Etoposide, 270 mg/m2 Vorinostat + Data Migration | Vorinostat 270 mg/m2; Etoposide 100 mg/m2 + Data Migration |
| Period Title: Overall Study | |||||
| STARTED | 7 | 3 | 3 | 9 | 5 |
| COMPLETED | 6 | 3 | 3 | 9 | 5 |
| NOT COMPLETED | 1 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Phase II Dose | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | 100 mg/m2 Etoposide, 125 mg/m2 Vorinostat + Data Migration | 100 mg/m2 Etoposide, 160 mg/m2 Vorinostat + Data Migration | 100 mg/m2 Etoposide, 210 mg/m2 Vorinostat + Data Migration | 100 mg/m2 Etoposide, 270 mg/m2 Vorinostat + Data Migration | Vorinostat 270 mg/m2; Etoposide 100 mg/m2 + Data Migration | Total of all reporting groups |
| Overall Participants | 7 | 3 | 3 | 9 | 5 | 27 |
| Age (years) [Median (Full Range) ] | ||||||
| Median (Full Range) [years] |
11
|
12
|
11.7
|
10.2
|
13.6
|
13
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
3
42.9%
|
1
33.3%
|
3
100%
|
4
44.4%
|
3
60%
|
14
51.9%
|
| Male |
4
57.1%
|
2
66.7%
|
0
0%
|
5
55.6%
|
2
40%
|
13
48.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
33.3%
|
1
11.1%
|
2
40%
|
4
14.8%
|
| Not Hispanic or Latino |
7
100%
|
3
100%
|
2
66.7%
|
8
88.9%
|
3
60%
|
23
85.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
28.6%
|
1
33.3%
|
1
33.3%
|
1
11.1%
|
0
0%
|
5
18.5%
|
| White |
4
57.1%
|
2
66.7%
|
2
66.7%
|
8
88.9%
|
4
80%
|
20
74.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
2
7.4%
|
| Region of Enrollment (Count of Participants) | ||||||
| United States |
7
100%
|
3
100%
|
3
100%
|
9
100%
|
5
100%
|
27
100%
|
Outcome Measures
| Title | To Establish the Dose Limiting Toxicity (DLT) |
|---|---|
| Description | of the novel combination vorinostat and etoposide in pediatric patients with refractory solid tumors including tumors of the central nervous system. The Toxicity will be evaluated according to NCI CTCAE Version 4.0. |
| Time Frame | Patients will be assessed in 3-week cycles. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected |
| Arm/Group Title | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Phase II Dose |
|---|---|---|---|---|---|
| Arm/Group Description | 100 mg/m2 Etoposide, 125 mg/m2 Vorinostat (n=7) | 100 mg/m2 Etoposide, 160 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 210 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 270 mg/m2 Vorinostat (n=9) | Vorinostat 270 mg/m2; Etoposide 100 mg/m2 (n=5) |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | To Establish the Maximum Tolerated Dose (MTD) |
|---|---|
| Description | of the novel combination vorinostat and etoposide in pediatric patients with refractory solid tumors including tumors of the central nervous system. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected |
| Arm/Group Title | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Phase II Dose |
|---|---|---|---|---|---|
| Arm/Group Description | 100 mg/m2 Etoposide, 125 mg/m2 Vorinostat (n=7) | 100 mg/m2 Etoposide, 160 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 210 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 270 mg/m2 Vorinostat (n=9) | Vorinostat 270 mg/m2; Etoposide 100 mg/m2 (n=5) |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | To Establish the Efficacy (CR (Complete Response) + PR (Partial Response) Rate) |
|---|---|
| Description | of the novel combination vorinostat and etoposide in pediatric patients with relapsed/refractory sarcoma. Evaluation for response will be determined by Revised RECIST guideline |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected |
| Arm/Group Title | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Phase II Dose |
|---|---|---|---|---|---|
| Arm/Group Description | 100 mg/m2 Etoposide, 125 mg/m2 Vorinostat (n=7) | 100 mg/m2 Etoposide, 160 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 210 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 270 mg/m2 Vorinostat (n=9) | Vorinostat 270 mg/m2; Etoposide 100 mg/m2 (n=5) |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | To Evaluate the Efficacy (CR (Complete Response) + PR (Partial Response) Rate) |
|---|---|
| Description | of the novel combination vorinostat and etoposide in pediatric patients enrolled in the phase I component of the study. Evaluation for response will be determined by Revised RECIST guideline. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected |
| Arm/Group Title | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Phase II Dose |
|---|---|---|---|---|---|
| Arm/Group Description | 100 mg/m2 Etoposide, 125 mg/m2 Vorinostat (n=7) | 100 mg/m2 Etoposide, 160 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 210 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 270 mg/m2 Vorinostat (n=9) | Vorinostat 270 mg/m2; Etoposide 100 mg/m2 (n=5) |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | To Evaluate the Biologic Effects Using Histone Acetylation, Gene Expression Profiling, and Histone Phosphorylation Profiling. |
|---|---|
| Description | of the novel combination of vorinostat and etoposide in pediatric patients with refractory solid tumors including central nervous system tumors |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected |
| Arm/Group Title | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Phase II Dose |
|---|---|---|---|---|---|
| Arm/Group Description | 100 mg/m2 Etoposide, 125 mg/m2 Vorinostat (n=7) | 100 mg/m2 Etoposide, 160 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 210 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 270 mg/m2 Vorinostat (n=9) | Vorinostat 270 mg/m2; Etoposide 100 mg/m2 (n=5) |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
Adverse Events
| Time Frame | 1 year | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Phase II Dose | |||||
| Arm/Group Description | 100 mg/m2 Etoposide, 125 mg/m2 Vorinostat (n=7) | 100 mg/m2 Etoposide, 160 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 210 mg/m2 Vorinostat (n=3) | 100 mg/m2 Etoposide, 270 mg/m2 Vorinostat (n=9) | Vorinostat 270 mg/m2; Etoposide 100 mg/m2 (n=5) | |||||
All Cause Mortality |
||||||||||
| Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Phase II Dose | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/7 (71.4%) | 2/3 (66.7%) | 1/3 (33.3%) | 4/9 (44.4%) | 3/5 (60%) | |||||
Serious Adverse Events |
||||||||||
| Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Phase II Dose | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/7 (42.9%) | 3/3 (100%) | 1/3 (33.3%) | 3/9 (33.3%) | 4/5 (80%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anemia | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Cardiac disorders | ||||||||||
| Sinus tachycardia | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Colitis | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Nausea | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Vomiting | 1/7 (14.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/9 (0%) | 0/5 (0%) | |||||
| General disorders | ||||||||||
| Death NOS | 1/7 (14.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Fever | 1/7 (14.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Infections and infestations | ||||||||||
| Catheter related infection | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Infections and infestations - Other, specify | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/5 (0%) | |||||
| Sepsis | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Investigations | ||||||||||
| Lymphocyte count decreased | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Neutrophil count decreased | 2/7 (28.6%) | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 2/5 (40%) | |||||
| Platelet count decreased | 2/7 (28.6%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/5 (20%) | |||||
| White blood cell decreased | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/5 (20%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Hypercalcemia | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Hypernatremia | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Bone pain | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Nervous system disorders | ||||||||||
| Headache | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Urinary tract obstruction | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Respiratory failure | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Phase II Dose | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | 3/3 (100%) | 3/3 (100%) | 9/9 (100%) | 5/5 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anemia | 5/7 (71.4%) | 0/3 (0%) | 2/3 (66.7%) | 2/9 (22.2%) | 3/5 (60%) | |||||
| Febrile neutropenia | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Leukocytosis | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Cardiac disorders | ||||||||||
| Sinus tachycardia | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Hearing impaired | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Vertigo | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Eye disorders | ||||||||||
| Optic nerve disorder | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Nausea | 2/7 (28.6%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/9 (11.1%) | 1/5 (20%) | |||||
| Vomiting | 1/7 (14.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Diarrhea | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Constipation | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Colitis | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Dry mouth | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Gastric hemorrhage | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Mucositis oral | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| General disorders | ||||||||||
| Fatigue | 1/7 (14.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 2/9 (22.2%) | 1/5 (20%) | |||||
| Fever | 1/7 (14.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Chills | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Death NOS | 1/7 (14.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Pain | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/5 (20%) | |||||
| Hepatobiliary disorders | ||||||||||
| Portal vein thrombosis | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Infections and infestations | ||||||||||
| Anorectal infection | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Catheter related infection | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Conjunctivitis | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Infections and infestations - Other, specify | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/5 (0%) | |||||
| Sepsis | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Skin infection | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Upper respiratory infection | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Investigations | ||||||||||
| White blood cell decreased | 7/7 (100%) | 1/3 (33.3%) | 2/3 (66.7%) | 5/9 (55.6%) | 3/5 (60%) | |||||
| Neutrophil count decreased | 7/7 (100%) | 0/3 (0%) | 3/3 (100%) | 6/9 (66.7%) | 3/5 (60%) | |||||
| Platelet count decreased | 6/7 (85.7%) | 0/3 (0%) | 1/3 (33.3%) | 4/9 (44.4%) | 2/5 (40%) | |||||
| Lymphocyte count decreased | 5/7 (71.4%) | 1/3 (33.3%) | 2/3 (66.7%) | 5/9 (55.6%) | 5/5 (100%) | |||||
| Aspartate aminotransferase increased | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 0/5 (0%) | |||||
| Alanine aminotransferase increased | 2/7 (28.6%) | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 0/5 (0%) | |||||
| Activated partial thromboplastin time prolonged | 2/7 (28.6%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/5 (20%) | |||||
| Blood bilirubin increased | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Creatinine increased | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| INR increased | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Urine output decreased | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Weight loss | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/5 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Anorexia | 2/7 (28.6%) | 0/3 (0%) | 1/3 (33.3%) | 2/9 (22.2%) | 2/5 (40%) | |||||
| Hypernatremia | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Hypocalcemia | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Hypokalemia | 2/7 (28.6%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Hyponatremia | 2/7 (28.6%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Hypophosphatemia | 1/7 (14.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 1/5 (20%) | |||||
| Dehydration | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Hyperglycemia | 2/7 (28.6%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Hypermagnesemia | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Hypoalbuminemia | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/5 (40%) | |||||
| Hypocalcemia | 2/7 (28.6%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/5 (40%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Myalgia | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Back pain | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Bone pain | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/5 (20%) | |||||
| Pain in extremity | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Nervous system disorders | ||||||||||
| Headache | 0/7 (0%) | 2/3 (66.7%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Abducens nerve disorder | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 0/5 (0%) | |||||
| Ataxia | 1/7 (14.3%) | 1/3 (33.3%) | 0/3 (0%) | 2/9 (22.2%) | 0/5 (0%) | |||||
| Dizziness | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Dysarthria | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Dysgeusia | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Facial nerve disorder | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Muscle weakness left-sided | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Muscle weakness right-sided | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Nervous system disorders - Other, specify | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Nystagmus | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Oculomotor nerve disorder | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Peripheral sensory neuropathy | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Pyramidal tract syndrome | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Seizure | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Somnolence | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Depression | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 1/5 (20%) | |||||
| Insomnia | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Renal and urinary disorders | ||||||||||
| Urinary tract obstruction | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Aspiration | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/5 (0%) | |||||
| Hypoxia | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Respiratory failure | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Alopecia | 1/7 (14.3%) | 0/3 (0%) | 2/3 (66.7%) | 0/9 (0%) | 3/5 (60%) | |||||
| Skin & subcutaneous tissue disorders Other, spec | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/5 (0%) | |||||
| Vascular disorders | ||||||||||
| Hypertension | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/5 (0%) | |||||
| Hypotension | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/5 (20%) | |||||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Tanya Trippett, MD |
|---|---|
| Organization | Memorial Sloan Kettering Cancer Center |
| Phone | 1-833-MSK-KIDS |
| trippet@mskcc.org |
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