Fasting Mimicking Diet (FMD) in Conjunction With Chemotherapy in Advanced Ovarian Cancer

NCT05921149 | Not Yet Recruiting DMC

• 1 other identifier: EH22-383
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

Rates of grade 3-4 toxicity with carboplatin and paclitaxel chemotherapy range 26-84%. Interventions to reduce toxicity are needed. Short term fasting protects against toxic effects of chemotherapy without decreasing efficacy. In a prospective clinical trial of breast cancer patients randomized to FMD or regular diet during chemotherapy, less antiemetic was required in the FMD group; radiographic and pathologic responses were better in this group. This trial tests whether platinum-taxane chemotherapy combined with a FMD in advanced and recurrent ovarian, fallopian tube and primary peritoneal cancer patients is associated with decreased toxicity and/ or improved tumor response to therapy.

Conditions

Ovarian Cancer; Chemotherapeutic Toxicity

Outcome Measures

Primary Outcomes (6)

• To determine whether the combination of standard of care platinum-taxane chemotherapy with a FMD compared to a regular diet is associated with decreased gastrointestinal (GI) toxicity in advanced and recurrent ovarian cancer patients.

  Toxicities and adverse events will be graded and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), v5.0 and will be compared between the two study groups. The following toxicity summaries will be used to compare the diet and non-diet group: Any of the following Grade 2+ GI symptomatic toxicities (nausea and vomiting, anorexia, constipation or diarrhea, mucositis, stomatitis) experienced. The NCI CTCAE has a specific scale (graded 1-5) for each toxicity which can be used objectively to compare different drug toxicities.

  6 months

• To determine whether the combination of standard of care platinum-taxane chemotherapy with a FMD compared to a regular diet is associated with decreased neurotoxicity in advanced and recurrent ovarian cancer patients.

  Toxicities and adverse events will be graded and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), v5.0 and will be compared between the two study groups. The following toxicity summaries will be used to compare the diet and non-diet group: Any Grade 2+ neuropathy experienced. The NCI CTCAE has a specific scale (graded 1-5) for each toxicity which can be used objectively to compare different drug toxicities.

  6 months

• To determine whether the combination of standard of care platinum-taxane chemotherapy with a FMD compared to a regular diet is associated with decreased hematologic toxicity in advanced and recurrent ovarian cancer patients.

  Toxicities and adverse events will be graded and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), v5.0 and will be compared between the two study groups. The following toxicity summaries will be used to compare the diet and non-diet group: Any Grade 3+ hematologic toxicity experienced. The NCI CTCAE has a specific scale (graded 1-5) for each toxicity which can be used objectively to compare different drug toxicities.

  6 months

• To determine whether the combination of standard of care platinum-taxane chemotherapy with a FMD compared to a regular diet is associated with improved quality of life (QOL) in advanced and recurrent ovarian cancer patients

  The primary QOL question examines whether chemotherapy plus FMD is associated with improved physical function and reduced chemotherapy-related side effects/ symptoms compared to chemotherapy administered with a regular diet. QOL and side effects/ symptoms of chemotherapy will be recorded using the Functional Assessment of Cancer Therapy (FACT) ovarian cancer questionnaire and compared between the study groups.

  6 months

• To determine whether the combination of standard of care platinum-taxane chemotherapy with a FMD compared to a regular diet is associated with improved QOL specifically with regards to less neuropathy in advanced and recurrent ovarian cancer patients

  This specific QOL question examines whether chemotherapy plus FMD is associated with improved physical function and reduced chemotherapy-related neuropathy compared to chemotherapy administered with a regular diet. QOL as impacted by neuropathy, specifically will be recorded using the FACT/ Gynecologic Oncology Group (GOG)-Neurotoxicity (Ntx) 4-item subscale and compared between the two study groups.

  6 months

• To determine whether the combination of standard of care platinum-taxane chemotherapy with a FMD compared to a regular diet is associated with improved QOL specifically with regards to less fatigue in advanced and recurrent ovarian cancer patients

  This specific QOL question examines whether chemotherapy plus FMD is associated with improved physical function and reduced fatigue compared to chemotherapy administered with a regular diet. QOL as impacted by fatigue, specifically, will be assessed using the 7-item Patient Reported Outcomes Measurement Information System (PROMIS) fatigue short form and compared between the two study groups.

  6 months

Secondary Outcomes (6)

• To describe the safety and tolerability of a concurrent FMD, including patient compliance to diet, with platinum-taxane chemotherapy in advanced and recurrent ovarian cancer patients.

  6 months

• To compare radiographic tumor response to therapy in advanced and recurrent ovarian cancer patients treated with the combination of platinum-taxane chemotherapy and a FMD versus a regular diet.

  6 months

• To compare tumor response to therapy using a serum biomarker in advanced and recurrent ovarian cancer patients treated with the combination of platinum-taxane chemotherapy and a FMD versus a regular diet.

  6 months

• To compare tumor pathologic response to therapy in advanced ovarian cancer patients treated with the combination of platinum-taxane chemotherapy and a FMD versus a regular diet.

  6 months

• To measure the progression free survival (PFS) at 2 and 5 years in each group.

  2 and 5 years

Study Arms (2)

Carboplatin and paclitaxel with standard diet

ACTIVE COMPARATOR

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6-10 cycles in the absence of disease progression or unacceptable toxicity. A standard diet is consumed throughout each cycle of therapy.

Drug: Carboplatin; Drug: Paclitaxel; Dietary Supplement: Standard diet

Carboplatin and paclitaxel with fasting mimicking diet (FMD)

EXPERIMENTAL

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6-10 cycles in the absence of disease progression or unacceptable toxicity. A fasting mimicking diet (FMD) is consumed beginning 3 days prior to chemotherapy and on the day of chemotherapy (days -2, -1, 0 and 1 of each cycle).

Dietary Supplement: Fasting Mimicking Diet (Xentigen by L'Nutra); Drug: Carboplatin; Drug: Paclitaxel

Interventions

Fasting Mimicking Diet (Xentigen by L'Nutra) DIETARY_SUPPLEMENT

L-Nutra Xentigen is a product which will provide all the food to be consumed by subjects during 3 days prior to chemotherapy and for 24 hours after chemotherapy. Xentigen is a plant-based diet program designed to attain fasting-like effects while providing both macro- and micronutrients to minimize the burden of fasting and adverse effects. The FMD consists of 100% ingredients that are generally regarded as safe (GRAS) and comprises proprietary vegetable-based soups and broths, energy bars, energy drinks, cracker snacks, herbal teas, and supplements. The FMD consists of a 4-day regimen that provides approximately 1100 kilocalories for the first day and approximately 500 kilocalories per day for the second to the fourth day. Subsequently, a day 5 of transition diet (approximately 800 kilocalories) is provided to avoid the refeeding syndrome.

Carboplatin and paclitaxel with fasting mimicking diet (FMD)

Carboplatin DRUG

Given IV

Carboplatin and paclitaxel with fasting mimicking diet (FMD); Carboplatin and paclitaxel with standard diet

Paclitaxel DRUG

Given IV

Carboplatin and paclitaxel with fasting mimicking diet (FMD); Carboplatin and paclitaxel with standard diet

Standard diet DIETARY_SUPPLEMENT

Normal diet

Carboplatin and paclitaxel with standard diet

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• All patients with advanced ovarian, fallopian tube and primary peritoneal carcinomas deemed appropriate candidates for neoadjuvant chemotherapy and patients with recurrent, platinum-sensitive disease (as defined by an interval of at least 6 months following completion of last platinum-based chemotherapy prior to disease relapse or progression)
• ECOG Performance Status of 0, 1 or 2.
• Adequate bone marrow reserve (absolute neutrophil count (ANC) ≥1.5 x 109/L and platelet count ≥100 x 109/L).
• Adequate renal function defined as creatinine ≤1.5 x laboratory upper limit of normal (ULN).
• Adequate hepatic function defined as:
• Bilirubin ≤1.5 x ULN ALT and AST ≤3 x ULN
• BMI ≥19 kg/m2

You may not qualify if:

• Patients with malnutrition and/ or BMI \<19
• Patients with active eating disorders (as identified by history of pre-enrollment nutrition screen)
• Diabetes mellitus requiring medication management (both insulin and non-insulin requiring). Patients with diabetes mellitus controlled by diet alone (i.e. patients not requiring anti-glycemic medications) are NOT excluded and are eligible for participation.
• Allergy to component of fasting mimicking diet (FMD)
• Patients with recurrent ovarian, fallopian tube and primary peritoneal carcinomas with relapse within 6 months of completion of last platinum-based chemotherapy regimen (i.e. patients with platinum-resistant disease)

Sponsors & Collaborators

• Endeavor Health: lead
• L-Nutra Inc: collaborator

Study Sites (1)

NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

Related Publications (9)

• de Groot S, Pijl H, van der Hoeven JJM, Kroep JR. Effects of short-term fasting on cancer treatment. J Exp Clin Cancer Res. 2019 May 22;38(1):209. doi: 10.1186/s13046-019-1189-9.

  PMID: 31113478 BACKGROUND

• Di Biase S, Longo VD. Fasting-induced differential stress sensitization in cancer treatment. Mol Cell Oncol. 2015 Dec 10;3(3):e1117701. doi: 10.1080/23723556.2015.1117701. eCollection 2016 May.

  PMID: 27314084 BACKGROUND

• Raffaghello L, Lee C, Safdie FM, Wei M, Madia F, Bianchi G, Longo VD. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8215-20. doi: 10.1073/pnas.0708100105. Epub 2008 Mar 31.

  PMID: 18378900 BACKGROUND

• Lee C, Longo VD. Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients. Oncogene. 2011 Jul 28;30(30):3305-16. doi: 10.1038/onc.2011.91. Epub 2011 Apr 25.

  PMID: 21516129 BACKGROUND

• Cheng CW, Adams GB, Perin L, Wei M, Zhou X, Lam BS, Da Sacco S, Mirisola M, Quinn DI, Dorff TB, Kopchick JJ, Longo VD. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014 Jun 5;14(6):810-23. doi: 10.1016/j.stem.2014.04.014.

  PMID: 24905167 BACKGROUND

• Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, Pistoia V, Wei M, Hwang S, Merlino A, Emionite L, de Cabo R, Longo VD. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med. 2012 Mar 7;4(124):124ra27. doi: 10.1126/scitranslmed.3003293. Epub 2012 Feb 8.

  PMID: 22323820 BACKGROUND

• Dorff TB, Groshen S, Garcia A, Shah M, Tsao-Wei D, Pham H, Cheng CW, Brandhorst S, Cohen P, Wei M, Longo V, Quinn DI. Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC Cancer. 2016 Jun 10;16:360. doi: 10.1186/s12885-016-2370-6.

  PMID: 27282289 BACKGROUND

• Bauersfeld SP, Kessler CS, Wischnewsky M, Jaensch A, Steckhan N, Stange R, Kunz B, Bruckner B, Sehouli J, Michalsen A. The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study. BMC Cancer. 2018 Apr 27;18(1):476. doi: 10.1186/s12885-018-4353-2.

  PMID: 29699509 BACKGROUND

• de Groot S, Lugtenberg RT, Cohen D, Welters MJP, Ehsan I, Vreeswijk MPG, Smit VTHBM, de Graaf H, Heijns JB, Portielje JEA, van de Wouw AJ, Imholz ALT, Kessels LW, Vrijaldenhoven S, Baars A, Kranenbarg EM, Carpentier MD, Putter H, van der Hoeven JJM, Nortier JWR, Longo VD, Pijl H, Kroep JR; Dutch Breast Cancer Research Group (BOOG). Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. Nat Commun. 2020 Jun 23;11(1):3083. doi: 10.1038/s41467-020-16138-3.

  PMID: 32576828 BACKGROUND

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Mary T Jenkins Vogel, MD

  Endeavor Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michele Britto, RN

CONTACT

(847) 570-2109; mbritto@northshore.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 23, 2023
• First Posted: June 27, 2023
• Study Start: May 25, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2031
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)