Therapeutic Targeting of Stress Factors in Ovarian Cancer Patients

Inclusion Criteria:1. Histologic diagnosis of invasive epithelial ovarian cancer, primary peritoneal carcinoma, fallopian tube cancer. Histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified. However, the histologic features must be compatible with primary Müllerian epithelial adenocarcinoma. Patients with low grade invasive epithelial ovarian cancers may participate.

2. Stages II-IV of the above cancer

3. Patients having undergone a suboptimal or optimal tumor debulking

4. Gynecologic Oncology Group performance status 0-2

5. Patients must have adequate:

1. Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1500/ml.
2. Platelets greater than 100,000/ml
3. Renal function: Creatinine <1.5 x institutional upper limit normal
4. Hepatic function: Bilirubin less than or equal to 1.5 x institutional upper limit normal; SGOT and alkaline phosphatase less than or equal to 2.5 x institutional upper limit normal.
5. Neurologic function: Neuropathy (sensory and motor) less than or equal to grade 1 according to Common Toxicity Criteria for Adverse Events version 3 (CTCAE).

6. Blood coagulation parameters: PT such that international normalized ratio (INR) is <1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for the management of venous thrombosis including pulmonary embolus) and a PTT <1.2 times institutional upper limit of normal.

   6. Surgery must be scheduled at least 72 hours in advance in order for the patient to take at least 48 hours of prescribed Propranolol.

   7. An approved informed consent and authorization permitting release of personal health information must be signed by patient or guardian.

   8. Age > 18 years

   9. Patients of childbearing age must have a negative pregnancy test.

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Exclusion Criteria:a. Patients who receive neoadjuvant chemotherapy for their ovarian, primary peritoneal, or fallopian tube cancer are excluded.

b. Patients with non-epithelial ovarian tumors, borderline epithelial ovarian tumor, or recurrent invasive epithelial ovarian, low grade ovarian cancer, primary peritoneal, or fallopian tube cancer treated with surgery only (such as patients with stage IA or IB). Patients with a prior diagnosis of a borderline tumor that was surgically resected and who subsequently develop an unrelated new invasive epithelial ovarian, primary peritoneal, or fallopian tube cancer are eligible, provided that they have not received chemotherapy for any tumor.

c. Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded. Prior radiation therapy for localized cancer of the breast, head and neck, or skin is permitted provided that it was completed more than 3 years prior to registration, and the patient remains free of recurrent or metastatic disease.

d. Patients with a synchronous primary endometrial cancer, or a past history of primary endometrial cancer are excluded unless all of the following conditions are met: stage not greater than stage IA; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO grade 3 lesions.

e. Patients who have received targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management of their primary peritoneal, ovarian, or fallopian tube cancer. Patients cannot receive concurrent bevacizumab or other targeted therapy as part of their primary chemotherapy.

f. With the exception of non-melanoma skin cancer and other specific malignancies as noted above, patients with other invasive malignancies who had (or have) any evidence of the other cancer present with the last five years or whose previous cancer treatment contraindicates this protocol therapy are excluded.

g. Metastases to the ovaries from other organs except fallopian tube or primary peritoneal carcinoma

h. Use of systemic glucocorticoids such as Prednisone or Decadron in the last month

i. Inability to accurately answer questions (e.g. dementia, brain metastases) or speak English

j. Cirrhosis of the liver

k. Patients with a GOG Performance status 3 or 4

l. Patients under the age of 18

m. Comorbid conditions: Addison's disease, autoimmune hepatitis, hepatitis B, hepatitis C, AIDS or HIV, lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis.

n. Any patients already on beta-blockers or contraindicated to receive beta-blockers. Refer to section 5.48

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