Neuroblastoma
Conditions
Brief summary
The purpose of this study is to test the feasibility (ability to be done) of an experimental test to help plan your cancer treatment. This study plan is not studying the effectiveness of the proposed combinations of therapy for your cancer that you may receive after the experimental testing. This study will look at an experimental technology to determine a tumor's molecular makeup (gene expression profile). This technology (called OncInsights) is being used to discover new ways to understand cancers and potentially predict the best treatments for patients with cancer in the future. The experimental technology has not been approved by the U.S. Food and Drug Administration.
Interventions
DEVICEGuided Therapy
A total of 14 eligible neuroblastoma 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 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
Giselle Sholler
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically proven neuroblastoma and confirmation of refractory or recurrent disease with histologic confirmation at diagnosis or at the time of recurrence/progression * Patients must be age \> 12 months and ≤ 21 at initial diagnosis. * Life expectancy must be more than 3 months * If measurable disease, this must be 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% are eligible to enroll. * Current disease state must be one for which there is currently no known curative therapy * Lansky or KarnofskyScore must be more than 50 * Patients without bone marrow metastases must have an ANC \> 750/μl and platelet count \> 50,000/μl * Adequate liver function must be demonstrated, defined as: * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND * SGPT (ALT) \< 10 x upper limit of normal (ULN) for age * No other significant organ toxicity defined as \> Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events NCI-CTCAE V4.0 * 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 patients 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
* Patients who have received any chemotherapy within the last 7 days prior to enrollment and 14 days prior to study treatment start date. * Patients who have received any radiotherapy within the last 30 days must have another site of disease to follow. * Patients receiving anti-tumor therapy for their disease or any investigational drug concurrently * Patients 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. * Patients 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 patient's ability to sign or the legal guardian's ability to sign the informed consent, and patient's ability to cooperate and participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants That Are Able to Meet Feasibility Parameters. | 1 year | Feasibility parameter defined as: Enrollment onto study, quality mRNA obtained, gene chip completed, tumor board held, medical monitor review and approval, 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 | 1 year | To determine the safety of allowing a molecular tumor board to determine individualized treatment plans |
| Overall Response Rate (ORR) of Participants Using RECIST Criteria | 1 year | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Activity of Treatments Chosen Based on Progression Free Survival (PFS) | 1 year | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
Countries
United States
Participant flow
Recruitment details
This was an open label, multi-center prospective feasibility study in patients with refractory or recurrent neuroblastoma that enrolled at NMTRC centers across the country between 8/11/2011 and 11/26/2012.
Participants by arm
| Arm | Count |
|---|---|
| Guided Therapy All subjects receive guided therapy in therapeutic combination (up to 4 agents) provided it includes medications contained in the study report. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | benign tumor types found at biopsy | 2 |
Baseline characteristics
| Characteristic | Guided Therapy |
|---|---|
| Age, Categorical <=18 years | 15 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
Percentage of Participants That Are Able to Meet Feasibility Parameters.
Feasibility parameter defined as: Enrollment onto study, quality mRNA obtained, gene chip completed, tumor board held, medical monitor review and approval, start of treatment by 21 days post biopsy/surgical resection date, and then completion of 1 cycle of therapy.
Time frame: 1 year
Population: All subjects had soft tissue disease in which biopsy was possible. Two subjects were deemed ineligible due to benign tumor type after biopsy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Guided Therapy | Percentage of Participants That Are Able to Meet Feasibility Parameters. | 100 percentage of participants |
Secondary
Activity of Treatments Chosen Based on Progression Free Survival (PFS)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Guided Therapy | Activity of Treatments Chosen Based on Progression Free Survival (PFS) | 59 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: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Guided Therapy | Number of Participants With Adverse Events as a Measure of Safety | 12 participants |
Secondary
Overall Response Rate (ORR) of Participants Using RECIST Criteria
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Guided Therapy | Overall Response Rate (ORR) of Participants Using RECIST Criteria | 7 percentage of participants with PR or CR |