Combined Program of Supervised Physical Exercise and Nutritional Counseling in Ovarian Cancer Patients on Frontline Maintenance Treatment With PARP Inhibitors

Prior treatment

• History of significant cardiovascular disease within 6 months prior to enrollment:
  • History of NCI CTCAE v5.0 Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class ≥ II.
  • High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate ≥100/min at rest, significant ventricular arrhythmia \[ventricular tachycardia\], or higher-grade atrioventricular \[AV\]-block, such as second-degree AV-block Type 2 \[Mobitz II\] or third-degree AV-block).
  • Myocardial infarction or ischemic disease,
  • Clinically significant valvular heart disease.
  • Ischemic or hemorrhagic stroke,
  • Thromboembolic events,
  • Peripheral vascular disease,
  • Aortic aneurysm, aortic dissection.
• Active infection and/or fever ≥ 38,5ºC within 7 days prior to initiation of the program requiring systemic antibiotics (excluding uncomplicated urinary tract infection).
• Patient has undergone any major surgical procedure within 3 weeks prior to screening or is planned during the program.

Other illness

• Women with diagnosis of recurrent ovarian cancer.
• Serous, non-healing wound, ulcer or bone fracture.
• Active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder or coagulopathy.
• Central nervous system disease.
• Pre-existing uncontrolled hypertension as documented by two baseline blood pressure readings taken at least five minutes apart, defined as systolic BP ≥ 140 or diastolic BP ≥ 90 mm Hg pressure.
• Patient has underlying chronic lung disease, chronic obstructive pulmonary disease, metastatic lung disease, pleural effusions or pneumonitis.
• Extensive non-oncological bone disease or presence of long-bones metastases or other symptomatic bone metastatic disease.

Lab values

• Known QT interval corrected by the Fridericia Correction Formula values of \>470msec; patient who is known to have congenital prolonged QT syndromes; or patient who is on medication known to cause prolonged QT interval on ECG.
• Patient had received a transfusion (platelets or red blood cells) or colony-stimulating factors (e.g., granulocyte macrophage colony-stimulating factor or recombinant erythropoietin) within 4 weeks before the exercise initiation.

Other

• Patient requires recurrent (≥ 1 per month) fluid drainage (eg, paracentesis, thoracocentesis, pericardiocentesis) or patient requires fluid drainage of ≥ 500 mL within 4 weeks of the expected date of exercise initiation.
• Significant peripheral sensory or motor neuropathy that could interfere with exercise program at investigator discretion.
• Patient who are pregnant, breastfeeding, or expecting to conceive children during program.

• Women ≥ 18 years old.
• High grade serous or endometrioid ovarian, primary peritoneal or fallopian tube cancer.
• Provide written informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Stage III-IV according to International Federation of Gynecology and Obstetrics (FIGO) staging system.
• Life expectancy of ≥ 6 months.
• Maintenance treatment with PARPi after response to first-line platinum-based chemotherapy, initiated at least 4 weeks prior to the informed consent signature.
• Patient is clinically stable and anticipate remaining on therapy for the duration of the exercise program.
• Patient is willing to provide a tumor tissue sample either collected from a prior biopsy or cytoreductive/debulking surgery occurring at any time since diagnosis, if available.
• Patients with sufficient digital capacity at the investigator's discretion.
• Ability and willingness to comply with the study protocol for the duration of the study and with follow-up procedures.
• Have adequate baseline function within 28 days of enrollment:
  • Platelets ≥ 100 × 109/L
  • Absolute neutrophil count (ANC) ≥ 1500/mm3
  • Hemoglobin ≥ 9 g/dL or 5.6 mmol/L
  • Aspartate transaminase and alanine transaminase ≤2.5 × upper limit of normal (ULN), \<5 × ULN in patients with known liver metastases
  • Serum total bilirubin ≤ 1.5 × ULN
  • 1.5-3.0 × ULN may be included with appropriate starting dose adjustment to 200 mg niraparib daily.
  • Creatinine \<1.5 × ULN or estimated glomerular filtration rate (GFR) ≥50 ml/min by Cockcroft-Gault.