Nutrition Interventions for Pediatric Cancer

(POINT Trial)

Overseen By Amanda M Harrington, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Corey Hawes

Must not be taking: Oral supplements, Orexigenics

Disqualifiers: Enteral nutrition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

45 Participants Needed

Trial Summary

What is the purpose of this trial?

Nearly 60% of pediatric patients diagnosed with cancer develop malnutrition caused by a combination of disease burden, side effects of chemotherapy, and the intensity of cancer treatment. These patients are known to have an increased risk of infection, treatment-related toxicity, inferior clinical outcomes, and increased risk of mortality. Malnutrition may progress to cancer cachexia, characterized by anorexia, increased inflammation, decreased fat, and decreased muscle mass with subsequent weight loss, which is associated with decreased overall survival. The goal of the proposed research is to determine changes in body composition, weight status, and nutritional status between common nutrition interventions including oral nutrition supplements (ONS), appetite stimulants, and enteral nutrition (EN) among pediatric cancer patients. A secondary goal of this research is to utilize the findings to develop clinical nutrition guidelines for this patient population. The specific objective of the research proposed is to solve the lack of evidence to adequately treat nutritional deficits in the pediatric oncology population. Without this data, there is a lack of clinical consistency in the initiation and selection of appropriate nutrition interventions to provide a more definitive pathway of care. This study can help formulate a clinical guideline for this patient population before, during, and after treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using or have used enteral nutrition, oral supplements, or appetite stimulants.

What data supports the effectiveness of the drug Cyproheptadine and other treatments in the clinical trial for pediatric cancer?

Dronabinol, a component of the treatment, has been shown to improve appetite in patients with AIDS and is used to manage anorexia and weight loss in cancer, although it is not specifically approved for cancer-related anorexia. Cyproheptadine and other pharmacologic strategies have been tested for reversing anorexia and weight loss in cancer patients, but megestrol acetate is the only agent consistently effective in improving appetite and weight. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Dronabinol (a form of THC) has been studied for safety in people with HIV/AIDS, showing some serious side effects like confusion and anxiety, but no significant differences in adverse events compared to other treatments. Cyproheptadine has been used safely as an appetite stimulant in children with cystic fibrosis. ^{4 6 7 8 9}

How does the nutritional intervention treatment for pediatric cancer differ from other treatments?

This treatment focuses on addressing malnutrition in children with cancer, which is a common issue during intensive cancer treatment due to factors like anorexia and altered taste. Unlike standard cancer treatments, this approach aims to improve nutritional status and quality of life, potentially reducing treatment-related complications and supporting overall well-being. ^{5 8 10 11 12}

Research Team

Corey J Hawes, DCN, RD, CSO, CNSC, LD

Principal Investigator

University of Kentucky, Kentucky Children's Hospital

Eligibility Criteria

This trial is for children newly diagnosed with cancer who haven't used enteral nutrition, oral supplements, or appetite stimulants before. It aims to help those at risk of malnutrition due to the effects of their illness and treatment.

Inclusion Criteria

My child has recently been diagnosed with cancer.

Exclusion Criteria

Current use or history of enteral nutrition

I am currently taking or have taken dietary supplements.

I have used or am using appetite-altering drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline ultrasound and biomarkers are taken at enrollment. Participants receive standard of care medical nutrition therapy counseling.

1 week

1 visit (in-person)

Randomization and Treatment

Participants are randomized to receive oral nutrition supplements, appetite stimulants, or enteral nutrition if they lose >10% of diagnosis weight. Ultrasounds and biomarkers are taken at randomization, 1 month, and 3 months after randomization.

3 months

Multiple visits (in-person) for assessments and interventions

Follow-up

Participants are monitored for safety and effectiveness after treatment. Measurements include body composition, biomarkers, and physical activity.

3 months

Regular visits (in-person) every 1-2 weeks

Treatment Details

Interventions

• Cyproheptadine
• Dronabinol
• Oral Nutrition Supplement
• Tube Feed

Trial Overview The study tests how different nutritional strategies affect body composition and weight in pediatric cancer patients. It compares oral supplements, appetite drugs like Dronabinol and Cyproheptadine, tube feeding, and standard care.

Participant Groups

Group I: Oral Nutrition Supplements Experimental Treatment 1 Intervention

Those receiving ONS will be prescribed a standard ONS (1.0 kcal per mL) that will meet a minimum of 50% of estimated energy needs to promote weight gain but allow for continued regular dietary intakes. The ONS will be prescribed as 8oz (240mL) per dose at least once a day, but up to six times per day depending on estimated nutrient needs.

Group II: Enteral Nutrition Experimental Treatment 1 Intervention

Those randomized to EN will have a feeding tube placed and started on tube feeds via a designated pump for overnight feeds, meeting at least 50% of estimated energy needs to allow for continued regular dietary intakes during the day.

Group III: Appetite Stimulants Experimental Treatment 2 Interventions

Those receiving age-appropriate appetite stimulants will be provided either cyproheptadine or olanzapine. Subjects will be given cyproheptadine if they fall between the ages of 2-12 years of age and olanzapine if they are \>12 years of age or older.

Group IV: Control Active Control 1 Intervention

Standard of Care who have either weight gain, weight maintenance, or weight loss \<10%.

Who Is Running the Clinical Trial?

Corey Hawes

Lead Sponsor

Trials

1

Recruited

50+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Findings from Research

Nutritional counseling and food supplements can help patients with cancer and AIDS who experience anorexia and weight loss, but severe anorexia often persists despite these interventions.

Among various pharmacologic treatments tested, megestrol acetate has shown the most promise in improving appetite and weight in cancer and AIDS patients, while dronabinol has been effective specifically for appetite enhancement in AIDS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical approaches to nutritional support in cancer. Tchekmedyian, NS.[2019]

Cannabinoid therapies, including pharmaceuticals and botanical forms, are versatile treatment options for patients with malignant diseases, effectively addressing symptoms like pain, chemotherapy-induced nausea, and anorexia.

These therapies not only improve quality of life for cancer patients but may also enhance adherence to conventional treatments like chemotherapy and radiation, potentially modifying the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A user's guide to cannabinoid therapies in oncology. Maida, V., Daeninck, PJ.[2019]

Megestrol acetate has been shown to be an effective and well-tolerated treatment for reversing anorexia in cancer patients, with significant improvements in appetite and food intake observed in large-scale trials involving over 600 participants.

The efficacy of megestrol acetate increases with dosage, with optimal doses ranging from 160 to 800 mg/day, and it works through both behavioral and metabolic mechanisms, impacting energy expenditure and appetite.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutrition in advanced cancer: anorexia as an outcome variable and target of therapy. Tchekmedyian, NS., Halpert, C., Ashley, J., et al.[2017]

Dronabinol, a synthetic form of THC, effectively increases appetite and reduces vomiting by acting on specific brain centers, making it a potential treatment for anorexia and weight loss in HIV/AIDS patients.

While dronabinol is FDA-approved for treating anorexia in HIV/AIDS, it currently lacks approval for cancer-related anorexia, highlighting a gap in treatment options for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer. Badowski, ME., Yanful, PK.[2020]

Among 13,375 pediatric patients with solid tumors, 26.5% were diagnosed with malnutrition, highlighting a significant prevalence of malnutrition during cancer treatment, particularly in those with adrenal and CNS tumors.

Patients with malnutrition experienced longer hospital stays and higher rates of emergency department visits and opioid use, indicating that better identification and treatment of malnutrition could improve clinical outcomes in pediatric oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Malnutrition identification and management variability: An administrative database study of children with solid tumors. Runco, DV., Stanek, JR., Yeager, ND., et al.[2022]

In a study involving 10 experienced marijuana smokers, oral Delta-9-tetrahydrocannabinol (Delta(9)-THC) was found to be chosen more often than a placebo, indicating some reinforcing effects, although participants selected it less than 50% of the time.

Both doses of Delta(9)-THC (10 mg and 20 mg) led to significant increases in positive subjective effects, impaired psychomotor performance, and increased heart rate, suggesting potential safety concerns alongside its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure. Hart, CL., Haney, M., Vosburg, SK., et al.[2022]

In a study involving 7 HIV-positive marijuana smokers, high doses of dronabinol (10 mg QID) were found to safely increase caloric intake and improve sleep quality, but only during the first 8 days of treatment.

Participants experienced sustained mood enhancement over the 16-day study, indicating that while dronabinol is effective, there may be a need for higher doses to maintain its appetite-stimulating effects due to the development of tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study. Bedi, G., Foltin, RW., Gunderson, EW., et al.[2022]

In a study of 15 pediatric patients with cystic fibrosis, cyproheptadine (CH) significantly improved nutrition status, as indicated by a mean increase in BMI z-score of +0.91 over 12 months, compared to a decrease of -0.52 in the previous year.

There was also a trend towards improved lung function during the 12 months of CH treatment, suggesting potential additional benefits, although this was not statistically significant (p = 0.07).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyproheptadine as an appetite stimulant in children with cystic fibrosis. Grunert, J., van der Haak, N., La Vanda, C., et al.[2021]

In a study of 52 patients with HIV wasting syndrome, megestrol acetate significantly increased weight over 12 weeks, with the highest gain seen in those taking 750 mg/day, while dronabinol alone led to weight loss.

Both drugs were generally safe, with no significant differences in adverse events among treatment groups, although dronabinol was associated with central nervous system side effects, and megestrol acetate was linked to changes in liver enzymes and hyperglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. Timpone, JG., Wright, DJ., Li, N., et al.[2013]

Children with cancer have unique nutritional needs that require careful consideration and support as part of their overall treatment plan.

The American Academy of Pediatrics formed a Task Force to evaluate these needs and develop nutritional intervention strategies, highlighting the importance of addressing nutritional risks to improve outcomes for pediatric cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Special nutritional needs of children with malignancies: a review. Mauer, AM., Burgess, JB., Donaldson, SS., et al.[2017]

Malnutrition is common during intensive cancer treatment in children due to factors like anorexia and the effects of chemotherapy, but nutritional support can improve well-being and immune function, potentially impacting survival rates.

While there is no strong evidence that nutritional support directly fights cancer, it is essential to provide it alongside cancer treatments to support overall health and recovery, especially after therapy is completed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of nutritional intervention on nutritional status, quality of life and survival. Van Eys, J.[2007]

In a study involving 260 undernourished children with cancer, those receiving ready-to-use therapeutic food (RUTF) showed significantly greater weight gain (77.8% vs. 64.2%) and improved fat mass compared to those receiving standard nutritional therapy (SNT).

Children on the RUTF regimen experienced fewer treatment-related toxicities, including severe infections (10.6% vs. 31%) and severe mucositis (11% vs. 23.8%), indicating that RUTF not only improves nutritional status but also enhances safety during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ready-to-use therapeutic food in malnourished children with cancer: Results of a randomized, open-label phase 3 trial. Prasad, M., Tandon, S., Gala, R., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical approaches to nutritional support in cancer. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A user's guide to cannabinoid therapies in oncology. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Nutrition in advanced cancer: anorexia as an outcome variable and target of therapy. [2017]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Malnutrition identification and management variability: An administrative database study of children with solid tumors. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Cyproheptadine as an appetite stimulant in children with cystic fibrosis. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Special nutritional needs of children with malignancies: a review. [2017]

11. United States pubmed.ncbi.nlm.nih.gov

Benefits of nutritional intervention on nutritional status, quality of life and survival. [2007]

12. United States pubmed.ncbi.nlm.nih.gov

Efficacy of ready-to-use therapeutic food in malnourished children with cancer: Results of a randomized, open-label phase 3 trial. [2022]