Intermittent Fasting Accompanying Chemotherapy in Gynecological Cancers

Study Overview
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Brief Summary
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The aim of this trial is an evaluation of the effectiveness of intermittent fasting as a supplementary therapy in patients with breast cancer and ovarian cancer in respect to quality of life, reduction of side effects and possible reduction in tumor progression.

Detailed Description
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Chemotherapy (CT) is a basic element in the therapy of gynecological oncologic diseases besides surgery, antibody therapy, anti-hormonal therapy and radiation. The chemotherapeutic intervention can be experienced physically and psychologically as a severe stress due to unwanted acute and also relevant long term side effects. It is even possible that because of severe side effects the CT can not be continued and main goals of the therapy like tumor reduction or elimination can not be achieved. Except of some medicinal approaches (such as antiemetics) or therapeutic exercise, not many therapeutic approaches are known to help reduce CT induced side effects. Against this background it is important to identify and scientifically evaluate new approaches to reduce the side effects of CT. The aim of this study is to verify the effectiveness of intermittent fasting as a potentially helpful supportive therapy in CT. In a prior pilot study of our institute with 34 breast- and ovarian cancer patients showed beneficial effects of an intermittent fasting of 72-84 h parallel to the application of the CT (manuscript submitted in Cancer Science). The results of this confirmatory study are therefore of potentially high clinical relevance for all chemotherapeutically treated patients. Long term goal: This study can lead to the improvement of tolerance and effectiveness of chemotherapeutic tumor therapy through accompanying intense nutritional therapy interventions. Beyond that it can be the starting point of a following multi-center randomized controlled study. A large variety of animal experimental studies as well as three smaller pilot studies suggest that intermittent fasting can reduce the unwanted side effects of CT and enhance the quality of life. It is being speculated that the anti-tumor effect of fasting is enhanced through the reduction of the Insulin-like growth factor-1 (IGF-1) and mTOR as well as p53-signalling molecules (differential stress resistance). But it is still unclear whether the possible beneficial effect that intermittent fasting shows can only be reached by subtotal caloric restriction or a significant reduction of the intake of animal proteins and refined sugar could also cause a similar decrease in IGF-1. Against this background this confirmatory study aims to test the hypothesis that CT in the adjuvant and neoadjuvant treatment of breast- and ovarian cancer is better tolerable under intermittent fasting than under a normo-caloric vegan and sugar-reduced diet.

Official Title
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Intermittent Fasting Accompanying Chemotherapy in Gynecological Cancers - a Randomized, Controlled, Two-armed Intervention Study

Conditions
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Breast Cancer, Ovarian Cancer

Intervention / Treatment
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* Other: Fasting
* Other: Vegan


Participation Criteria
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Eligibility Criteria
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Diagnosed, gynecological, malignant tumor disease (non-metastatic ovarian or breast cancer). Other inclusion criteria: Age 18-75 years Cancer is treated conventionally with an adjuvant or neo-adjuvant protocol with at least 4 CT cycles The following CTs are considered for breast carcinoma: - (EC, Sparano) 4 x Epirubicin and Cyclophosphamide, followed by 12 cycles Paclitaxel weekly - (AC, Henderson) 4 x Doxorubicin, cyclophosphamide, followed by 4 cycles Docetaxel every three weeks If the recruitment rate is not reached, further CT protocols can be accepted. CT for patients with ovarian cancer: According to current protocols, at least 4 planned cycles. For the study a maximum of 8 cycles are considered (except therapy with Taxol). Exclusion Criteria: Reduction in CT dose compared to usual dosage Excessive underweight (BMI <19kg / m2) or actual weight reduction > 3kg or > 5kg in the last 1 or 3 months. Pre-existing eating disorder (Anorexia nervosa, Bulimia) Renal insufficiency (creatinine> 2mg / dl) Severe disease or other disease with a significant reduction in mobility and overall vitality Diabetes mellitus No inclusion in other study protocol Lack of email address and Internet access (due to electronic CRF)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fasting<br>60-72 h-modified fasting (36-48 h before and 24 h after chemotherapy) | Other: Fasting<br>* Patients follow a modified fasting regime of 60-72 h (36-48 h before and 24 h after CT) with a dietary energy supply of 350-400kcal per day with vegetable juices during the first four cycles of CT. During the rest of the CT cycles they will observe two days of caloric restriction (24 h before and after CT). Between CTs a mainly vegetarian diet will be performed and the patients are encouraged to follow a pattern of time restricted feeding with 14 h fasting over night at least for six days a week. The patients will receive an individual nutrition training by trained nutritionists.<br>|
| Active Comparator: Vegan<br>60-72 h-vegan diet (36-48 h before and 24 h after chemotherapy) | Other: Vegan<br>* Patients follow a 60-72 h vegan diet with sugar restriction (36-48 h before and 24 h after CT) during the first four cycles of CT. During the rest of the CT cycles they will observe two days of vegan and sugar-restricted diet (24 h before and after CT). Between CTs a mainly vegetarian diet will be performed. The patients will receive an individual nutrition training by trained nutritionists.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FACT-G | Summarized change of FACT-G score | Date of inclusion (baseline), day -2 and +7 at each chemotherapy (CT) in triweekly cycles/-2 days at each CT in weekly cycles and +7 after the last weekly CT, 4 months after inclusion, 3 weeks after end of CT and 1, 2 and 3 years after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remissions | Number of histologically proven complete remissions (ypT0ypN0 bzw. ypT0/is) after neoadjuvant CT | From date of randomization until the date of surgery | 
| Millar Payne classification | Histological classification according to Millar Payne scale | after surgery/histological examination, an average 6 months after intervention start | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fasting, Vegan