The Effects of Exercise on Distress, Quality of Life, and Biomarkers in Ovarian Cancer Survivors

OUTLINE:

Patients are randomized to 1 of 2 arms.

ARM I (EXERCISE INTERVENTION): Patients meet with exercise physiologist for 1, 60 minute session. Patients then receive individualized exercise prescription with goal of moderate aerobic exercise over 150 minutes per week at home for up to 24 weeks. Patients also receive telephone-based motivational support by exercise physiologist weekly for 24 weeks.

ARM II (CONTROL GROUP): Patients maintain habitual levels of physical activity and receive general education material about ovarian cancer and survivorship for 24 weeks. After 24 weeks, patients are offered exercise intervention.

• Exercise Counseling (Other): Meet with exercise physiology
• Aerobic Exercise (Other), also known as Aerobic Activity, aerobic exercise: Receive prescription for moderate aerobic exercise
• Physiological Support (Other): Receive motivational support via telephone care
• Quality-of-Life Assessment (Other), also known as Quality of Life Assessment: Ancillary studies
• Questionnaire Administration (Other): Ancillary studies
• Best Practice (Other), also known as best practice, standard of care, standard of care, standard therapy: Undergo habitual level of physical activity

Primary outcomes

• Change in Quality of Life Measured Using the RAND 36-item Short Form Health Survey Physical Component Score [Baseline up to 24 weeks]: Will be measured using the RAND 36-item Short Form Health Survey Physical Component Score. Mean change from baseline to 24 weeks between the exercise intervention and control group in the RAND 36-item Short Form Health Survey Physical Component Score. RAND 36-Item Short Form assesses eight subscales including physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, general health perceptions, and perceived change in health. Possible scores for each subscale range from 0 to 100. The Physical Component Score (PCS) is an aggregate of the eight subscales using a standardized algorithm, with a mean of 50 and standard deviation of 10 in the general US population. Possible scores range from 20 to 60, with higher scores indicating a better quality of life.
• Change in Distress, Measured Using the Perceived Stress Scale [Baseline to 24 weeks]: Will be measured using the Perceived Stress Scale. Mean change from baseline to 24 weeks between the exercise intervention and control group in the Perceived Stress Scale. The Perceived Stress Scale is a 10 item questionnaire with a total score range of 0-40. Higher total scores indicate higher distress.
• Change in Distress, Measured Using the Hospital Anxiety and Depression Scale - Anxiety Subscale [Baseline to 24 weeks]: Will be measured using the Hospital Anxiety and Depression Scale - Anxiety subscale. Mean change from baseline to 24 weeks between the exercise intervention and control group in the Hospital Anxiety and Depression Scale - anxiety subscale. The Hospital Anxiety and Depression Scale includes 2 subscales: anxiety and depression. The Hospital Anxiety and Depression Scale - anxiety subscale total scores range from 0 to 21; higher scores indicated greater severity of anxiety symptoms.
• Change in Distress, Measured Using the Hospital Anxiety and Depression Scale - Depression Subscale [Baseline to 24 weeks]: Will be measured using the Hospital Anxiety and Depression Scale - Depression sub scale. Mean change from baseline to 24 weeks between the exercise intervention and control group in the Hospital Anxiety and Depression Scale - Depression subscale. The Hospital Anxiety and Depression Scale includes 2 subscales: anxiety and depression. The Hospital Anxiety and Depression Scale - Depression subscale total scores range from 0 to 21; higher scores indicated greater severity of depression symptoms.
• Change in IL-6 (Biomarker of Angiogenesis) [Baseline to 24 weeks]: Mean change from baseline to 24 weeks between the exercise intervention and control group in mean levels of IL-6.
• Change in VEGF (Biomarker of Angiogenesis) [Baseline to 24 weeks]: Mean change from baseline to 24 weeks between the exercise intervention and control group in mean levels of VEGF.
• Change in Nocturnal Cortisol (Biomarker of Chronic Stress) [Baseline to 24 weeks]: Mean change from baseline to 24 weeks between the exercise intervention and control group in mean level of evening salivary cortisol.

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Histologically or cytologically confirmed stage II-IV epithelial ovarian, fallopian tube, or peritoneal cancer. If site of origin cannot be specified, carcinoma of Mullerian origin may be included if most consistent with ovarian/fallopian tube/peritoneal origin rather than uterine origin. The following histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, clear cell carcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's tumor, undifferentiated carcinoma, carcinosarcoma, or adenocarcinoma not otherwise specified. Women with neoplasms of low malignant potential (borderline tumors) are not eligible.
* Subjects must have no evidence of disease, as defined by their treating oncologist, and with normal CA-125 (=< 35).
* Subjects must have completed primary surgery and adjuvant chemotherapy for treatment of ovarian, fallopian tube, of peritoneal cancer within one to six months of screening. Maintenance therapy will be allowed as long as the participant is in clinical remission- including hormonal agents, anti-angiogenesis agents, PARP inhibitors, and immunotherapy. Prior radiation therapy is allowed, as long as it has been completed within one to six months of screening. Subjects may have received prior therapies (including surgery, chemotherapy, radiation therapy) for other malignancies in the past.
* Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.
* Pregnancy and the need for contraception:

  * Participants with ovarian cancer have undergone hysterectomy with removal of ovaries and tubes as part of surgical treatment, and therefore do not have the potential to become pregnant.
* Ambulatory.
* Ability to understand and the willingness to sign a written informed consent document.
* Individuals participating in most other clinical trials are eligible provided their enrollment in the other trial does not impair their ability to participate in the physical activity interventions and study assessments required in this trial. The other clinical trial must not be a behavioral intervention trial.

Exclusion Criteria:

* Subjects who have had primary surgery, chemotherapy and/or radiation therapy within 4 weeks prior to screening. Subjects may have received other surgeries not performed for primary treatment (for example, removal of intraperitoneal port, laparoscopic cholecystectomy, etc.) within 1 month of screening as long as they do not have post-operative restrictions that would preclude participating in a moderate intensity exercise program once enrolled in the clinical trial.
* Self-reported inability to walk at least 2 blocks (at any pace).
* Prior brain metastasis is not an exclusion, as long as subject is in clinical remission.
* Uncontrolled or concurrent illness including, but not limited to: unstable angina pectoris, recent (within six months) myocardial infarction, uncontrolled cardiac arrhythmia, uncontrolled congestive heart failure, hypertrophic obstructive cardiomyopathy, uncontrolled hypertension (systolic > 200, diastolic > 120), conditions (cardiovascular, respiratory, or musculoskeletal disease or joint problems) that preclude moderate physical activity. Subjects with a history of cardiac arrest, or those with moderate/severe aortic or mitral stenosis may be eligible if their treating physician determines that moderate physical activity is safe. Moderate arthritis that does not preclude physical activity is not a reason for ineligibility. Individuals with lymphedema or peripheral neuropathy will not be excluded. They will be evaluated by the exercise physiologist for safety and modifications to the exercise prescription will be made as appropriate.
* Psychiatric illness/social situations that would limit compliance with study requirements.
* Already physically active > 90 minutes per week of moderate exercise.

Participant flow

Outcome results

• Change in Quality of Life Measured Using the RAND 36-item Short Form Health Survey Physical Component Score (Primary), Mean, score on a scale: Arm I (Aerobic Exercise) 4.37 +/- 0.99; Arm II (Habitual Level of Physical Activity) 4.61 +/- 2.02
• Change in Distress, Measured Using the Perceived Stress Scale (Primary), Mean, score on a scale: Arm I (Aerobic Exercise) -1.4 +/- 0.97; Arm II (Habitual Level of Physical Activity) 1.05 +/- 1.64
• Change in Distress, Measured Using the Hospital Anxiety and Depression Scale - Anxiety Subscale (Primary), Mean, score on a scale: Arm I (Aerobic Exercise) -1.15 +/- 0.56; Arm II (Habitual Level of Physical Activity) -0.15 +/- 0.72
• Change in Distress, Measured Using the Hospital Anxiety and Depression Scale - Depression Subscale (Primary), Mean, score on a scale: Arm I (Aerobic Exercise) -0.76 +/- 0.42; Arm II (Habitual Level of Physical Activity) -0.32 +/- 0.80
• Change in IL-6 (Biomarker of Angiogenesis) (Primary), Mean, pg/mL: Arm I (Aerobic Exercise) -0.57 +/- 2.03; Arm II (Habitual Level of Physical Activity) 0.09 +/- 0.54
• Change in VEGF (Biomarker of Angiogenesis) (Primary), Mean, pg/mL: Arm I (Aerobic Exercise) -37.3 +/- 41.84; Arm II (Habitual Level of Physical Activity) -82.2 +/- 36.35
• Change in Nocturnal Cortisol (Biomarker of Chronic Stress) (Primary), Mean, ug/dL: Arm I (Aerobic Exercise) 0.01 +/- 0.157; Arm II (Habitual Level of Physical Activity) 0.11 +/- 0.07

Adverse events

Time frame: 6 months

Limitations and caveats: Enrollment ended before meeting accrual goal due to the funding timeline, leading to smaller numbers of participants analyzed. Most participants completed the study after the COVID-19 pandemic began. The study continued for several years during the pandemic. Multiple surges occurred and there was variable timing of infections experienced by participants and their loved ones over the course of their 6 month study participation. Participants were not uniformly affected by the COVID-19 pandemic.

• Study Protocol and Statistical Analysis Plan (PDF, 2020-09-24)

• Kathryn Pennington, Principal investigator, University of Washington

NIH grants: R21CA215662