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

Официальное название

A Randomized Controlled Study of a Fasting Mimicking Diet (FMD) in Conjunction With Combination Carboplatin and Paclitaxel in the Treatment of Patients With Advanced or Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Cancer

Обзор

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.

Вмешательства

• Пищевая добавка Fasting Mimicking Diet (Xentigen by L'Nutra)
  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, ener
• Препарат Carboplatin
  Given IV
• Препарат Paclitaxel
  Given IV
• Пищевая добавка Standard diet
  Normal diet

Первичные конечные точки

• 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 6 months]

Вторичные конечные точки (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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 6 months]
• To measure the progression free survival (PFS) at 2 and 5 years in each group. [Срок оценки: 2 and 5 years]
• To measure the overall survival (OS) in each group. [Срок оценки: 5 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• NorthShore University HealthSystem — Evanston

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT05921149 · EH22-383

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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