Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)

Study Overview
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Brief Summary
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Toxicities related to pediatric cancer treatment can lead to significant illness, organ damage, treatment delays, increased health care cost, and decrease in quality of life. Such toxicities are largely due to tissue damage sustained by chemotherapy, and strategies designed to limit such cellular damage to normal tissues may reduce therapy-related morbidity and mortality. In addition to their in vitro and in vivo anti-cancer effects, naturally occurring soy isoflavones have anti-inflammatory and anti-oxidant properties, and have been shown to reduce side effects of therapy in adult oncology clinical trials. This study will examine the effect of genistein, the major isoflavone component in soybeans and the most extensively studied of the soy isoflavones, on short-term side effects of myelosuppressive chemotherapy in pediatric cancer patients. Subjects will be randomized to receive either: a) 30 mg genistein daily throughout chemotherapy Cycles 1 and 2 and placebo during chemotherapy Cycles 3 and 4; or b) placebo daily during chemotherapy Cycles 1 and 2 and 30 mg genistein daily during chemotherapy Cycles 3 and 4. Investigators hypothesize that subjects will have fewer short-term therapy-related side effects during cycles of chemotherapy given in conjunction with genistein supplementation than cycles given with placebo.

Detailed Description
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This is a multi-center, randomized, double blind, placebo-controlled crossover study to evaluate the effect of soy isoflavones on the short term untoward effects of myelosuppressive chemotherapy used to treat pediatric cancers. Newly diagnosed cancer patients aged 1-21 years will be registered to the study and informed consent will be obtained prior to any study-related procedures. Stratification will be based on length of chemotherapy cycles, between 14 day and 21 day cycles. Within strata registered subjects will be randomized 1:1 to one of two schedules: Arm A: Subjects will receive genistein daily throughout chemotherapy cycles 1 and 2, and placebo during chemotherapy cycles 3 and 4 Arm B: Subjects will receive placebo daily throughout chemotherapy cycles 1 and 2, and genistein during chemotherapy cycles 3 and 4 Subjects will be assessed for safety and efficacy during each cycle with clinical labs, cytokine panels, and physical exams. Drug compliance will be monitored by use of a patient diary as well as monitoring of serum genistein levels. Adverse events will be monitored starting on Cycle 1 Day 1 through 30 days following the last day of protocol therapy (genistein/placebo).

Official Title
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A Randomized, Placebo-Controlled Pilot Study of Genistein Supplementation in Pediatric Cancer Patients Receiving Myelosuppressive Chemotherapy

Conditions
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Germ Cell Tumor, Lymphoma, Childhood Lymphoma, Solid Tumor, Childhood Solid Tumor, Neuroblastoma, Ewing Sarcoma, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Rhabdomyosarcoma, Soft Tissue Sarcoma, Medulloblastoma, Wilms Tumor, Brain Neoplasms, Medulloblastoma, Childhood, Neuroectodermal Tumors, Primitive

Intervention / Treatment
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* Drug: Genistein
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Newly diagnosed solid tumor or lymphoma with histological verification Age 1 - 21 years at time of diagnosis Karnofsky/Lanksy performance score of ≥ 50 Able to tolerate enteral medication administration Planned chemotherapeutic regimen for a patient must meet all of the following criteria: A known myelosuppressive regimen which includes at least two of the following agents: actinomycin, carboplatin, cisplatin, cyclophosphamide, daunorubicin, doxorubicin, etoposide, ifosfamide, topotecan At least four consecutive cycles Cycle length is either 14 or 21 days Regimen must either alternate myelosuppressive chemotherapeutic agents in an X-Y-X-Y format, such that the same chemotherapy is given every other cycle (e.g. vincristine/doxorubicin/cyclophosphamide │ ifosfamide/etoposide), or repeat the same chemotherapeutic agents each cycle in an X-X-X-X format (e.g. repeated cycles of cisplatin/etoposide/bleomycin). Courses eligible for this trial may occur at any time during treatment provided that they are consecutive and follow the one of the described patterns. Non-myelosuppressive anti-neoplastic treatments will not be considered for the purposes of determining eligibility. Questions regarding whether or not a patient's chemotherapy plan meets inclusion criteria will be decided by the Study Chair. Informed consent or parental permission and assent obtained prior to trial-related activities Able and willing to comply with all study related procedures Women of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Exclusion Criteria Known allergy to soy or any soy-based food or supplement Unable or unwilling to discontinue consuming prohibited soy-based food or supplements while participating in this study Pre-existing neutropenia or neutrophil qualitative or quantitative disorder Pre-existing cytopenia or bone marrow failure syndrome History of gastric or duodenal ulcers or hyperacidity syndromes History of Human Immunodeficiency Virus (HIV) Has an active infection requiring systemic therapy Planned treatment does not include myelosuppressive chemotherapy Enrolled on a therapeutic or supportive care clinical trial within the last 30 days Current acute or chronic leukemia diagnosis Requires medication dosing via an enteral feeding tube that terminates in the duodenum or jejunum. (Enteral feeding tubes that terminate in the stomach are acceptable for study medication delivery.) Pregnant or breastfeeding woman Incarceration Secondary malignancy, i.e. the cancer for which the patient is presently or will be receiving treatment may not be a malignancy related to prior cancer therapy Any condition which might be worsened by estrogen, such as breast cancer, uterine cancer, ovarian cancer, endometriosis or uterine fibroids Any condition, in the investigator's opinion, that would compromise patient safety or study outcomes Anyone who, in the investigator's discretion, would be unwilling or unable to comply with study procedures

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Genistein followed by Placebo<br>Genistein daily throughout chemotherapy cycles 1 and 2, and placebo daily during chemotherapy cycles 3 and 4 | Drug: Genistein<br>* Estrogen-like compound (isoflavone) derived from soybeans<br>* Other names: i-cool tablets containing 30 mg geniVida™;Drug: Placebo<br>* Pill that contains no medicine<br>|
| Experimental: Arm B: Placebo followed by Genistein<br>Placebo daily throughout chemotherapy cycles 1 and 2, and genistein daily during chemotherapy cycles 3 and 4 | Drug: Genistein<br>* Estrogen-like compound (isoflavone) derived from soybeans<br>* Other names: i-cool tablets containing 30 mg geniVida™;Drug: Placebo<br>* Pill that contains no medicine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to neutrophil count recovery following myelosuppressive chemotherapy |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum marker levels of inflammation during cycles of chemotherapy |  | Once before treatment starts and then four more times while the study drug is being taken, an 8 - 16 week period if there are no chemotherapy delays | 
| Number of days that participants experience adverse events that are commonly caused by chemotherapy treatment |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Number of participants who experience adverse events that are commonly caused by chemotherapy treatment |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Number of times per participant that adverse events that are commonly caused by chemotherapy treatment occur |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Severity of adverse events that are commonly caused by chemotherapy treatment |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Number of days that participants are hospitalized or have prolonged hospitalization due to an adverse event |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Number of days that planned cancer treatment is delayed due to an adverse event |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Percent that planned cancer treatment doses are reduced due to an adverse event |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Number of days that antimicrobial treatment is administered |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Number of participants who are administered granulocyte-colony stimulating factor (G-CSF) |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Number of times per participant that granulocyte-colony stimulating factor (G-CSF) is administered |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Number of participants who are administered a blood product |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Number of times per participant that a blood product is administered |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 
| Number of times that a blood product is administered for anemia, decreased platelets, abnormal bleeding, or the subject's best interest |  | From the first date study drug is taken until the last date that study drug is taken, about 8 - 12 weeks if there are no chemotherapy delays | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genistein, Soy, Chemotherapy side-effects, Pediatric Cancer, Isoflavone