Caloric Restriction Diet for Sarcoma

Overseen By Joseph J Connolly

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

Trial Summary

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 data supports the effectiveness of the caloric restriction diet treatment for sarcoma?

Research shows that caloric restriction can slow down tumor growth in animals and may make cancer cells more sensitive to treatments like chemotherapy and radiation. Additionally, a study found that caloric restriction helped improve treatment response in leukemia patients by reducing cancer cell resistance. ^{1 2 3 4 5}

Is a very low-calorie diet generally safe for humans?

Very low-calorie diets (VLCDs) have been used for weight loss and are generally safe when properly monitored by healthcare professionals. However, there are concerns about potential risks like gallstones and heart rhythm problems if not managed correctly, so it's important to have medical supervision and high-quality supplements. ^{6 7 8 9 10}

How does the caloric restriction diet treatment for sarcoma differ from other treatments?

The caloric restriction diet is unique because it involves reducing calorie intake to potentially slow down cancer growth by affecting the tumor's environment and metabolism, unlike traditional treatments that often involve drugs or surgery. This dietary approach may also enhance the effectiveness of chemotherapy and radiotherapy while reducing their side effects. ^{1 4 11 12 13}

What is the purpose of this trial?

This study is being conducted to decrease the rate of surgical wound complications. The investigators are studying the effects that caloric restriction has on decreasing the rate of surgical wound complications.

Research Team

Santiago A Lozano-Calderón, MD,PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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

Normal blood counts within 45 days of enrollment

Normal chemistries within 45 days of enrollment

I am older than 18 years.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Nutrient restriction and radiation therapy for cancer treatment: when less is more. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Stratifying nutritional restriction in cancer therapy: Next stop, personalized medicine. [2021]

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

Caloric and nutrient restriction to augment chemotherapy efficacy for acute lymphoblastic leukemia: the IDEAL trial. [2022]

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

The evolution of very-low-calorie diets: an update and meta-analysis. [2009]

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

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

8. England 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. [2021]

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

Safety and efficacy of a multiphase dietetic protocol with meal replacements including a step with very low calorie diet. [2021]

10. England pubmed.ncbi.nlm.nih.gov

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

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Calorie Restriction for Cancer Prevention and Therapy: Mechanisms, Expectations, and Efficacy. [2022]

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

Influence of caloric intake on experimental carcinogenesis: a review. [2019]

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

Effects of caloric restriction and dietary fat on epithelial cell proliferation in rat colon. [2013]