Clinical trial NCT03162289: Intermittent Fasting Accompanying Chemotherapy in Gynecological Cancers
Official title: Intermittent Fasting Accompanying Chemotherapy in Gynecological Cancers - a Randomized, Controlled, Two-armed Intervention Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Cancer
Ovarian Cancer
Keywords: Fasting
Vegan
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2017-05-22
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: FACT-G
timeFrame: 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 outcomes:
measure: Complete remissions
timeFrame: From date of randomization until the date of surgery
measure: Millar Payne classification
timeFrame: after surgery/histological examination, an average 6 months after intervention start
Other outcomes:
measure: Trial outcome index score (TOI)
timeFrame: 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
measure: Total AC (FACT-B/FACT-O)
timeFrame: Date of inclusion (baseline), day -2 and +7 at each 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
measure: FACIT-F
timeFrame: Date of inclusion (baseline), day -2 and +7 at each 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
measure: FACT-Tax,FACT/GynecologicOncologyGroup-Ntx
timeFrame: Date of inclusion (baseline), day -2 and +7 at each 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
measure: Chemotherapy-Induced Peripheral Neuropathy Assessment Tool
timeFrame: Date of inclusion (baseline), day -2 and +7 at each 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
measure: Hospital Anxiety and Depression Scale
timeFrame: Date of inclusion (baseline), day -2 and +7 at each 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
measure: Side effects of CT
timeFrame: Date of inclusion (baseline), day -2 and +7 at each 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
measure: Weight
timeFrame: Timing varies according to individual therapy plan, Date of inclusion (baseline) and up to 3 years after inclusion
measure: BMI
timeFrame: Timing varies according to individual therapy plan, Date of inclusion (baseline) and up to 3 years after inclusion
measure: Blood panel
timeFrame: Timing varies according to individual therapy plan, Date of inclusion (baseline) and up to 3 years after inclusion
measure: Blood values for liver function
timeFrame: Timing varies according to individual therapy plan, Date of inclusion (baseline) and up to 3 years after inclusion
measure: Blood values for renal function (Krea, Hst.)
timeFrame: Timing varies according to individual therapy plan, Date of inclusion (baseline) and up to 3 years after inclusion
measure: IGF-1, Insulin, Blood glucose
timeFrame: Baseline, after 4 months and before each of the first 4 CTs meaning approx week 1,4,7 and 10 after intervention start
measure: Long-term explorative measurements: frequency of recurrence
timeFrame: 1, 2 and 3 years after baseline
measure: Long-term explorative measurements: e.g. polyneuropathy, cardiomyopathy
timeFrame: 1, 2 and 3 years after baseline
measure: ketone bodies
timeFrame: Baseline, after 4 months and before each of the first 4 CTs meaning approx week 1,4,7 and 10 after intervention start
measure: Elective items of the "Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: Baseline, 3 weeks after end of CT, 1,2,3 years after baseline
measure: Qualitative interviews in focus groups
timeFrame: Baseline, 6 months
Locations:
city: Freiburg im Breisgau
country: Germany
facility: Albert-Ludwigs-University of Freiburg
state: Baden-Württemberg
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg
state: Baden-Württemberg
city: Potsdam
country: Germany
facility: Ernst-von-Bergmann Klinikum, Klinik für Gynäkologie und Geburtshilfe
state: Brandenburg
city: Berlin
country: Germany
facility: Brustzentrum Charite Campus Mitte
city: Berlin
country: Germany
facility: Vivantes Brustzentrum
city: Berlin
country: Germany
facility: Charité Virchow Klinikum
city: Berlin
country: Germany
facility: Brustzentrum Krankenhaus Waldfriede
city: Berlin
country: Germany
facility: Charité Hochschulambulanz für Naturheilkunde am Immanuel Krankenhaus
Study officials:
affiliation: Study Principal Investigator Charite
name: Andreas Michalsen, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koppold-Liebscher D, Kessler CS, Steckhan N, Bahr V, Kempter C, Wischnewsky M, Hubner M, Kunz B, Paul M, Zorn S, Sari S, Jeitler M, Stange R, Michalsen A. Short-term fasting accompanying chemotherapy as a supportive therapy in gynecological cancer: protocol for a multicenter randomized controlled clinical trial. Trials. 2020 Oct 15;21(1):854. doi: 10.1186/s13063-020-04700-9.