Caloric Restriction Diet for Sarcoma

Overseen By Shreya Halur, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Metformin

Disqualifiers: Pregnancy, Other cancers, Diabetes, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a reduced-calorie diet can lower the risk of surgical wound problems in people with soft tissue sarcoma, a type of cancer in the lower legs. Participants will either follow a caloric restriction diet or maintain their normal diet to determine which is more effective. The trial seeks individuals with soft tissue sarcoma in their legs who plan to undergo radiation and surgery. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance surgical outcomes for future patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those currently on metformin therapy.

What prior data suggests that caloric restriction is safe for decreasing surgical wound complications?

Research has shown that eating fewer calories can benefit health, particularly for those with cancer. Studies have found that reducing calorie intake can enhance the effectiveness of cancer treatments like chemotherapy and radiation. As a result, patients might experience better outcomes from these treatments when they consume fewer calories.

One study involved participants following a very low-calorie diet of about 350 calories a day. This study, which included over 2,000 people, found that the diet was safe for most participants. This suggests that significantly cutting calories is generally well-tolerated.

Overall, while eating less might seem challenging, evidence indicates it can be done safely and may aid in cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for sarcoma, which typically involve surgery, chemotherapy, and radiation, the caloric restriction diet offers a unique approach by focusing on dietary modification. Researchers are excited about this method because it may influence cancer metabolism by reducing calorie intake, thus potentially slowing down tumor growth. This diet emphasizes precise control over calorie and protein consumption, distinguishing it from traditional therapies that directly target the tumor with drugs or radiation. By altering the body's nutritional environment, this approach could lead to new insights into non-invasive strategies for managing sarcoma.

What evidence suggests that a caloric restriction diet might be effective for reducing surgical wound complications in sarcoma patients?

This trial will compare a Caloric Restriction Diet with a Normal Diet for sarcoma patients. Research has shown that eating fewer calories might improve outcomes after surgery. Studies have found that reducing calorie intake can slow tumor growth and enhance the effectiveness of treatments like chemotherapy and radiation. Early findings suggest that patients who eat less may experience fewer complications after surgery. In animal studies, reducing calorie intake has also increased the effectiveness of radiation therapy. While more research is needed in humans, these early results are promising for sarcoma patients considering this diet. ^{1 3 4 6 7}

Who Is on the Research Team?

Santiago A Lozano-Calderón, MD,PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a confirmed soft tissue sarcoma in the lower extremities, who are not pregnant or breastfeeding, don't have diabetes or other cancers within the last 5 years, and aren't on metformin therapy. They must have normal organ function and blood counts, a BMI ≥ 20 kg/m2, and be scheduled for radiation followed by surgery.

Inclusion Criteria

I am older than 18 years.

I will receive radiation for soft tissue sarcoma in my leg before surgery.

My kidney and liver are functioning normally.

Exclusion Criteria

I have diabetes.

I have not been diagnosed with any other cancer in the last 5 years.

I am currently taking metformin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Radiation Therapy

Participants receive pre-operative radiation therapy as part of the treatment protocol

6 weeks

Dietary Intervention

Participants are randomized to either a caloric restriction diet or a normal diet

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 6 weeks, 3 months, and 6 months post-surgery

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Caloric Restriction Diet

Trial Overview The study tests if eating fewer calories can reduce surgical wound complications in sarcoma patients undergoing pre-operative radiation therapy. Participants will follow a caloric restriction diet before their tumor surgery to see if it helps improve outcomes.

How Is the Trial Designed?

Group I: Caloric Restriction Diet Experimental Treatment 1 Intervention

Patients will meet with the Registered Dietitian to discuss calorie, protein, and fluid needs.The dietitian will calculate calorie needs. * Calorie needs will be reduced by 30%. * Protein needs will be estimated based on 0.8g/kg BW and then reduced by 70%. * Dietitian will educate participants on electrolytes and fluid intake based on the reduced food intake.

Group II: Normal Diet Active Control 1 Intervention

Participant will follow a normal diet.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

NORCH (Nutrition Obesity Research Center at Harvard)

Collaborator

Trials

2

Recruited

60+

Published Research Related to This Trial

In a study of 6640 adults over one year, those on very-low-calorie diets (VLCD) experienced a significantly greater weight loss (-11.1 kg) compared to those on low-calorie diets (LCD) (-8.1 kg), but this came with increased risks.

The risk of developing symptomatic gallstones requiring hospital care was three times higher in the VLCD group compared to the LCD group, with 48 cases in VLCD versus 14 in LCD, indicating a notable safety concern for VLCDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of symptomatic gallstones and cholecystectomy after a very-low-calorie diet or low-calorie diet in a commercial weight loss program: 1-year matched cohort study. Johansson, K., Sundström, J., Marcus, C., et al.[2021]

Caloric restriction significantly reduces colonic cell proliferation (CCP), which is a marker for colon cancer risk, in both high-fat and low-fat diet groups of rats treated with a carcinogen.

While a high-fat diet did not increase CCP in the distal colon, it was associated with a higher tumor yield, indicating that dietary fat influences cancer risk differently than caloric intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of caloric restriction and dietary fat on epithelial cell proliferation in rat colon. Steinbach, G., Kumar, SP., Reddy, BS., et al.[2013]

Very low-calorie diets (VLCDs), providing 800 kcal/day or less, can lead to significant weight loss of 1.5 to 2.5 kg per week, with an average total loss of 20 kg over 12 to 16 weeks, which is more effective than standard low-calorie diets.

VLCDs are generally safe for moderately and severely obese patients when supervised by medical professionals, although long-term weight maintenance remains a challenge; incorporating behavioral therapy and physical activity can help improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very low-calorie diets. National Task Force on the Prevention and Treatment of Obesity, National Institutes of Health. [2022]

Calorie restriction (CR), which reduces calorie intake by 20%-40%, has been shown to increase longevity and may also enhance the effectiveness of cancer treatments like radiation and chemotherapy by altering key molecular pathways.

Laboratory and clinical evidence suggests that CR can make breast cancer cells more susceptible to standard treatments, indicating its potential as a complementary intervention in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutrient restriction and radiation therapy for cancer treatment: when less is more. Champ, CE., Baserga, R., Mishra, MV., et al.[2021]

Very-low-calorie diets (VLCDs) lead to significantly greater short-term weight loss compared to conventional low-calorie diets (LCDs), with participants losing an average of 16.1% of their initial weight versus 9.7% for LCDs.

However, after one year, the long-term weight loss results were similar for both VLCDs and LCDs, with VLCDs resulting in a 6.3% loss compared to 5.0% for LCDs, indicating that VLCDs do not provide a sustained weight loss advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolution of very-low-calorie diets: an update and meta-analysis. Tsai, AG., Wadden, TA.[2009]

A multiphasic dietary intervention including a very low calorie diet (VLCD) led to an average weight loss of 15.4% and significant reductions in fat mass among 24 obese patients over a 120-day period.

The study demonstrated a high safety profile and excellent compliance, with no adverse effects on liver or kidney function, indicating that this dietary approach is effective and well-tolerated for weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of a multiphase dietetic protocol with meal replacements including a step with very low calorie diet. Basciani, S., Costantini, D., Contini, S., et al.[2021]

Calorie restriction and its various forms, including intermittent fasting, show promise as potential adjuvant therapies for cancer by impacting tumor growth and metabolism, as supported by preclinical studies.

Preliminary clinical studies suggest that patients on reduced calorie diets may experience better outcomes and tolerance to chemotherapy and radiotherapy, indicating a beneficial role of calorie restriction in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calorie Restriction for Cancer Prevention and Therapy: Mechanisms, Expectations, and Efficacy. Vidoni, C., Ferraresi, A., Esposito, A., et al.[2022]

Caloric restriction significantly inhibits tumor growth, with the most effective results seen when restriction is maintained during both the initiation and promotion phases of tumor development.

A diet low in calories but high in fat is more effective at reducing tumor incidence compared to a high-calorie, low-fat diet, as demonstrated in studies with mice showing up to 61% fewer tumors with high fat, low calorie diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of caloric intake on experimental carcinogenesis: a review. Kritchevsky, D., Klurfeld, DM.[2019]

Very low calorie diets (VLCD) can be effective for weight loss, but maintaining that weight loss requires follow-up support, including behavior modification and increased physical activity.

Safety concerns have arisen from the use of liquid protein supplements, which were linked to deaths; however, monitoring and using high-quality protein supplements have mitigated these risks, based on clinical experience with over 4000 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very low calorie diets--history, safety and recent developments. Vertes, V.[2009]

In a study involving 172 women undergoing chemotherapy, intermittent energy restriction (IER) showed a trend towards greater weight and body fat reduction compared to continuous energy restriction (CER), particularly after adjusting for body water.

While the overall incidence of severe chemotherapy toxicities was similar between IER and CER, there was a trend indicating fewer severe toxicities in the IER group during later cycles of treatment, suggesting IER may help reduce treatment-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer. Harvie, M., Pegington, M., Howell, SJ., et al.[2022]

The IDEAL trial, involving 40 patients aged 10 to 21 with newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL), showed that a diet and exercise intervention did not significantly reduce overall fat mass gain but effectively reduced fat gain in overweight/obese patients by 8.2% (from +9.7% to +1.5%).

The intervention also significantly decreased the risk of minimal residual disease (MRD) after chemotherapy, with an odds ratio of 0.30, suggesting that caloric restriction through diet and exercise may enhance chemotherapy efficacy in B-ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caloric and nutrient restriction to augment chemotherapy efficacy for acute lymphoblastic leukemia: the IDEAL trial. Orgel, E., Framson, C., Buxton, R., et al.[2022]

Caloric restriction, even as low as 10%, significantly inhibits tumor growth in rodents, with a notable 40% caloric restriction leading to substantial reductions in mammary and colonic tumors.

Exercise also plays a crucial role in reducing tumor incidence, as sedentary rats showed a 108% higher rate of colon tumors compared to those that exercised regularly, highlighting the importance of both diet and physical activity in cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of caloric restriction and exercise on tumorigenesis in rats. Kritchevsky, D.[2020]

Nutrient restriction (NR), such as fasting or caloric restriction, shows promise in enhancing the effectiveness of cancer drugs by exploiting the metabolic vulnerabilities of cancer cells, which have a high demand for nutrients to support their growth.

The implementation of NR in clinical settings is complicated by factors like patient biology, cancer type, and treatment adherence, highlighting the need for systematic preclinical studies to identify effective NR and drug combinations and to personalize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stratifying nutritional restriction in cancer therapy: Next stop, personalized medicine. Krstic, J., Pieber, TR., Prokesch, A.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8551193/

Daily caloric restriction limits tumor growth more effectively ... Caloric restriction (CR) has been shown as an effective intervention to reduce tumorigenesis, but alternative less stringent dietary ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8749320/

Calorie Restriction for Cancer Prevention and Therapy Preliminary clinical studies show that patients subjected to a reduced nutrient/energy intake experience improved outcomes from chemo- and radiotherapy while ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02792270

Caloric Restriction In Sarcoma Patients Treated With Pre ... Caloric Restriction has been found to be a natural modifier of surgical outcomes. Participants will be randomize into the arms Caloric ...

4. research.jefferson.edu research.jefferson.edu/magazine/how-cutting-calories-could-transform-cancer-treatment.html

How Cutting Calories Could Transform Cancer Treatment She confirmed that starting animals on a calorie-restricted diet during radiation enhanced the therapy in models of breast cancer.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1044579X20302005

The effect of caloric restriction and fasting on cancer Increasing preclinical evidence indicates that caloric restriction (CR) and fasting might have anticancer effects by reducing tumor progression, enhancing ...

6. nature.com nature.com/articles/s41467-021-26431-4

Daily caloric restriction limits tumor growth more effectively ... Caloric restriction (CR) confers benefits on health and survival and delays cancer. However, due to CR's stringency, dietary alternatives ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7476366/

Fasting and Caloric Restriction in Cancer Prevention and ... Consuming a very-low-calorie diet of 350 kcal/day (an almost fasting-like approach) has been considered safe in a large cohort with over 2000 participants with ...