Brain Tumors, Medulloblastoma, Neuroblastoma, Rare Tumors
Conditions
Brief summary
The purpose of this study is to test the feasibility (ability to be done) of experimental technologies to determine a tumor's molecular makeup (gene expression profile) and mutations. This technology called the Pediatric Gene Analysis Platform includes a genomic report (gene expression profile) and a DNA Mutation Panel Report that are being used to discover new ways to understand cancers and potentially predict the best treatments for patients with cancer in the future.
Interventions
DEVICEGuided Therapy- Pediatric Gene Analysis Platform
A total of 48 neuroblastoma, brain tumor, and rare tumor patients who are refractory or relapsed on conventional therapy will be treated. Guided therapy will allow the use of any therapeutic combination (up to 4 agents) provided it includes medications contained in the study report. All patients will be followed for survival, disease response, progression and safety. All patients will be treated according to the discretion of the treating oncologist and study committee (minimum 3 oncologists and one pharmacist). Extent of disease will be measured and assessed for changes throughout the course of the study and at 6-8 week intervals (every 2 cycles).
Sponsors
Dell, Inc.
Giselle Sholler
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must have histologically proven neuroblastoma, brain tumor, or rare tumor and confirmation of refractory or recurrent disease with histologic confirmation at diagnosis or at the time of recurrence/progression * Subjects must be age \>12 months at enrollment. * Subjects must be age ≤ 21 years at initial diagnosis. * Subjects must have measurable disease as demonstrated by residual abnormal tissue at a primary or metastatic site measuring more than 1 cm in any dimension by standardized imaging (CT or MRI); tumor must be accessible for biopsy. Patients with bone marrow only disease expected to be \>75% tumor are eligible to enroll. * Current disease state must be one for which there is currently no known curative therapy * Lansky or Karnofsky Score must be more than 50 * Subjects without bone marrow metastases must have an ANC \> 750/μl * Adequate liver function must be demonstrated, defined as: 1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND 2. SGPT (ALT) \< 10 x upper limit of normal (ULN) for age * A negative serum pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses) * Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives (the pill), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended. * Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines. Voluntary consent for optional biology studies will be included.
Exclusion criteria
* Subjects who have received any cytotoxic chemotherapy within the last 7 days prior to enrollment and 14 days prior to study treatment start date. * Subjects who have received any radiotherapy to the primary sample site within the last 14 days (radiation may be included in treatment decision after biopsy). * Subjects receiving anti-tumor therapy for their disease or any investigational drug concurrently * Subjects with serious infection or a life-threatening illness (unrelated to tumor) that is \> Grade 2 (NCI CTCAE V4.0), or active, serious infections requiring parenteral antibiotic therapy. * Subjects with any other medical condition, including malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine Feasibility Using Days From the Date of Biopsy to Date of Start of Treatment | Date from biopsy to completion of 1 cycle of therapy, generally about 30 days | Days to treatment is one data point that will be used in order to determine feasibility. The definition of feasibility for this study will include: Enrollment onto study, RNA expression profile completed, DNA Mutation Panel completed, genomic analysis and report generation, tumor board held with treatment decision, treatment review completed and start of treatment by 21 days post biopsy/surgical resection date, and then completion of 1 cycle of therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety | Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 3 years. | To determine the safety of allowing a molecular tumor board to determine individualized treatment plans |
| Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Followed until off therapy, generally 3 years | To determine the activity of treatments chosen based on Overall response rate (ORR) using RESIST criteria. The assessment of response will include the initial measurable targets and will be performed after cycle 2, then after every other cycle. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI imaging and/or by MIBG or PET scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease, At least a 20% increase in the sum of the disease measurements for measurable lesions, Stable Disease, Neither sufficient decrease to qualify for PR or sufficient increase to qualify for PD from study entry. Overall Response (OR) = CR + PR. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Guided Therapy- Pediatric Gene Analysis Platform A total of 48 pediatric cancer (neuroblastoma, brain tumor, and rare tumor) patients who are refractory or relapsed on conventional therapy will be treated. Guided therapy will allow the use of any therapeutic combination (up to 4 agents) provided it includes medications contained in the study report. All patients will be followed for survival, disease response, progression and safety. All patients will be treated according to the discretion of the treating oncologist and study committee (minimum 3 oncologists and one pharmacist). Extent of disease will be measured and assessed for changes throughout the course of the study and at 6-8 week intervals (every 2 cycles).
Guided Therapy- Pediatric Gene Analysis Platform: A total of 48 neuroblastoma, brain tumor, and rare tumor patients who are refractory or relapsed on conventional therapy will be treated. Guided therapy will allow the use of any therapeutic combination (up to 4 agents) provided it includes medications contained in the study report. All patients will be followed for survival, disease response, progression and safety. All patients will be treated according to the discretion of the treating oncologist and study committee (minimum 3 oncologists and one pharmacist). Extent of disease will be measured and assessed for changes throughout the course of the study and at 6-8 week intervals (every 2 cycles). | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Consented but did not start therapy | 7 |
| Overall Study | Lack of Efficacy | 7 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Guided Therapy- Pediatric Gene Analysis Platform |
|---|---|
| Age, Categorical <=18 years | 49 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 9.7 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 39 Participants |
| Tumor Type refractory or relapsed rare tumors | 22 Participants |
| Tumor Type refractory/relapsed neuroblastoma | 22 Participants |
| Tumor Type relapsed or refractory brain tumors | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 45 |
| other Total, other adverse events | 43 / 45 |
| serious Total, serious adverse events | 21 / 45 |
Outcome results
Primary
Determine Feasibility Using Days From the Date of Biopsy to Date of Start of Treatment
Days to treatment is one data point that will be used in order to determine feasibility. The definition of feasibility for this study will include: Enrollment onto study, RNA expression profile completed, DNA Mutation Panel completed, genomic analysis and report generation, tumor board held with treatment decision, treatment review completed and start of treatment by 21 days post biopsy/surgical resection date, and then completion of 1 cycle of therapy.
Time frame: Date from biopsy to completion of 1 cycle of therapy, generally about 30 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stratum 1 | Determine Feasibility Using Days From the Date of Biopsy to Date of Start of Treatment | 12.2 Days |
| Stratum 2 | Determine Feasibility Using Days From the Date of Biopsy to Date of Start of Treatment | 19.9 Days |
| Stratum 3 | Determine Feasibility Using Days From the Date of Biopsy to Date of Start of Treatment | 14.9 Days |
Secondary
Number of Participants With Adverse Events as a Measure of Safety
To determine the safety of allowing a molecular tumor board to determine individualized treatment plans
Time frame: Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 3 years.
Population: All subjects that started at least one dose of therapy. Outcome measure was reported as an overall study result, and was not reported by cohort.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stratum 1 | Number of Participants With Adverse Events as a Measure of Safety | 43 Participants |
Secondary
Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans.
To determine the activity of treatments chosen based on Overall response rate (ORR) using RESIST criteria. The assessment of response will include the initial measurable targets and will be performed after cycle 2, then after every other cycle. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI imaging and/or by MIBG or PET scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease, At least a 20% increase in the sum of the disease measurements for measurable lesions, Stable Disease, Neither sufficient decrease to qualify for PR or sufficient increase to qualify for PD from study entry. Overall Response (OR) = CR + PR.
Time frame: Followed until off therapy, generally 3 years
Population: Analyzed population only includes evaluable subjects, defined as subjects that made it to an evaluation time point (scans at end of cycle 2), or had a documented progression of disease prior to evaluation time point.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stratum 1 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Complete Response | 1 Participants |
| Stratum 1 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Partial Response | 0 Participants |
| Stratum 1 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Stable Disease | 4 Participants |
| Stratum 1 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Progressive Disease | 12 Participants |
| Stratum 2 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Progressive Disease | 5 Participants |
| Stratum 2 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Complete Response | 2 Participants |
| Stratum 2 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Stable Disease | 0 Participants |
| Stratum 2 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Partial Response | 0 Participants |
| Stratum 3 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Progressive Disease | 8 Participants |
| Stratum 3 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Partial Response | 1 Participants |
| Stratum 3 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Stable Disease | 6 Participants |
| Stratum 3 | Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans. | Complete Response | 2 Participants |