Clinical trial NCT01504126: Propranolol Hydrochloride and Chemotherapy in Treating Patients With Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
Official title: Feasibility Study: Therapeutic Targeting of Stress Factors in Ovarian Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Fallopian Tube Clear Cell Adenocarcinoma
Fallopian Tube Endometrioid Adenocarcinoma
Fallopian Tube Mucinous Adenocarcinoma
Fallopian Tube Serous Adenocarcinoma
Fallopian Tube Undifferentiated Carcinoma
Ovarian Clear Cell Adenocarcinoma
Ovarian Endometrioid Adenocarcinoma
Ovarian Mucinous Adenocarcinoma
Ovarian Seromucinous Carcinoma
Ovarian Serous Adenocarcinoma
Ovarian Undifferentiated Carcinoma
Primary Peritoneal Serous Adenocarcinoma
Stage II Fallopian Tube Cancer AJCC v6 and v7
Stage II Ovarian Cancer AJCC v6 and v7
Stage IIA Fallopian Tube Cancer AJCC v6 and v7
Stage IIA Ovarian Cancer AJCC V6 and v7
Stage IIB Fallopian Tube Cancer AJCC v6 and v7
Stage IIB Ovarian Cancer AJCC v6 and v7
Stage IIC Fallopian Tube Cancer AJCC v6 and v7
Stage IIC Ovarian Cancer AJCC v6 and v7
Stage III Fallopian Tube Cancer AJCC v7
Stage III Ovarian Cancer AJCC v6 and v7
Stage III Primary Peritoneal Cancer AJCC v7
Stage IIIA Fallopian Tube Cancer AJCC v7
Stage IIIA Ovarian Cancer AJCC v6 and v7
Stage IIIA Primary Peritoneal Cancer AJCC v7
Stage IIIB Fallopian Tube Cancer AJCC v7
Stage IIIB Ovarian Cancer AJCC v6 and v7
Stage IIIB Primary Peritoneal Cancer AJCC v7
Stage IIIC Fallopian Tube Cancer AJCC v7
Stage IIIC Ovarian Cancer AJCC v6 and v7
Stage IIIC Primary Peritoneal Cancer AJCC v7
Stage IV Fallopian Tube Cancer AJCC v6 and v7
Stage IV Ovarian Cancer AJCC v6 and v7
Stage IV Primary Peritoneal Cancer AJCC v7
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Sprint for Life
First posted: 2012-01-05
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This early phase I trial studies giving propranolol hydrochloride with standard chemotherapy in treating patients with ovarian, primary peritoneal, or fallopian tube cancer. Biological therapies, such as propranolol hydrochloride, blocks certain chemicals that affect the heart and this may stimulate the immune system and allow the chemotherapy to kill more tumor cells.

Detailed description: PRIMARY OBJECTIVES:

I. To determine the feasibility of pharmacologic beta-adrenergic blockade in women with stages II-IV epithelial ovarian cancer patients (n=25) either during initial tumor reductive surgery and through the first six cycles of standard intravenous chemotherapy or during neoadjuvant chemotherapy followed by surgery and further chemotherapy (chemo) up to a total of 6 cycles.

SECONDARY OBJECTIVES:

I. To characterize the biobehavioral states of these patients by using the Functional Assessment of Chronic Illness and Therapy- Ovary (FACT-O), Hospital Anxiety and Depression Survey (HADS) and the Center for Epidemiologic Studies Depression Scale (CESD) and serum levels of angiogenic cytokines at points pre- and post-treatment with beta-blockers.

II. To follow patients for progression-free survival (PFS) and overall survival (OS).

TRANSLATIONAL OBJECTIVES:

I. Determining vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, and other cytokines levels in patients with ovarian cancer who are receiving beta-blockers and comparing these levels pre-treatment and during treatment with response.

OUTLINE:

Patients receive propranolol hydrochloride orally (PO) twice daily (BID) beginning 48-72 hours before treatment. Patients undergoing surgery resume propranolol hydrochloride post-operatively once oral drugs are tolerated and continue until completion of 6 cycles of chemotherapy. Patients undergoing neoadjuvant chemotherapy continue propranolol hydrochloride PO BID during 3 chemotherapy cycles pre-surgery and 3 cycles post-surgery. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Eligibility criteria: Inclusion Criteria:

* Suspected preoperative diagnosis of invasive epithelial ovarian cancer, primary peritoneal carcinoma, fallopian tube cancer based on imaging and cancer antigen (Ca) 125; 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; patients with primarily carcinoma histology but mixed features can be included; the surgically confirmed histologic features must be compatible with primary Mullerian epithelial adenocarcinoma
* Stages II-IV of the above cancer
* Patients to be scheduled for a planned tumor debulking
* Intention for chemotherapy administration at MD Anderson Cancer Center
* Zubrod performance status 0-2
* Absolute neutrophil count (ANC) \>= 1500/ml
* Platelets \> 100,000/mL
* Creatinine clearance (CrCl) \> 50 mL/min
* Bilirubin =\< 1.5 x institutional upper limit normal
* Serum glutamic oxaloacetic transaminase (SGOT) =\< 2.5 x institutional upper limit normal
* Alkaline phosphatase =\< 2.5 x institutional upper limit normal
* Neuropathy (sensory and motor) =\< grade 1 according to Common Toxicity Criteria for Adverse Events version 3 (CTCAE)
* Prothrombin time (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)
* Partial thromboplastin time (PTT) \< 1.2 times institutional upper limit of normal
* Pulse \>= 60 beat per minute (bpm)
* Systolic blood pressure (SBP) \> 110 mmHg; diastolic blood pressure (DBP) \>= 60 mmHg
* Normotensive individuals not already on beta blockers (may be on other anti hypertensives): SBP =\< 140, DBP =\< 90
* Surgery or neoadjuvant chemotherapy must be scheduled at least 72 hours in advance in order for the patient to take at least 48 hours of prescribed propranolol and have stable vital signs confirmed
* An approved informed consent and authorization permitting release of personal health information must be signed by patient or guardian
* Patients of childbearing age must have a negative pregnancy test
* Patients who receive neoadjuvant chemotherapy for their ovarian, primary peritoneal, or fallopian tube cancer

Exclusion Criteria:

* Patients with non-epithelial ovarian tumors that do not require adjuvant chemotherapy, 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; no stromal cancers or germ cell cancers or low malignant potential; patients found post operatively to have ineligible histology will be removed from the study
* 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
* 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 International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
* 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
* 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 within the last five years or whose previous cancer treatment contraindicates this protocol therapy are excluded
* Metastases to the ovaries from other organs except fallopian tube or primary peritoneal carcinoma
* Use of systemic glucocorticoids such as prednisone or Decadron in the last month
* Inability to accurately answer questions (e.g. dementia, brain metastases) or speak English or Spanish
* Cirrhosis of the liver
* Patients with a Zubrod performance status 3 or 4
* Comorbid conditions: Addison's disease, autoimmune hepatitis, hepatitis B, hepatitis C, acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV), lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis
* Any patients already on beta-blockers or contraindicated to receive beta-blockers
* Hypersensitivity to propranolol, or beta-blockers
* Uncompensated congestive heart failure
* Cardiogenic shock
* Severe sinus bradycardia; heart block, second or third degree or sick sinus syndrome (if no artificial pacemaker present)
* Severe hyperactive airway disease (chronic obstructive pulmonary disease, asthma)
* Any patients planning to receive Avastin or any other anti-angiogenic drugs
* Patients with brittle diabetes mellitus (DM); brittle diabetes mellitus is a type of diabetes when a person's blood glucose (sugar) level often swings quickly from high to low and from low to high; also called "unstable diabetes" or "labile diabetes"

Primary outcomes:
measure: Proportion of patients who successfully complete 6 cycles of chemotherapy with propranolol hydrochloride
timeFrame: Up to 6 months
Secondary outcomes:
measure: Changes in quality of life as measured by the Functional Assessment of Chronic Illness and Therapy- Ovary (FACT-O)
timeFrame: Baseline to up to 6 months
measure: Changes in mood state as measured by the Hospital Anxiety and Depression Survey (HADS)
timeFrame: Baseline to up to 6 months
measure: Progression-free survival (PFS)
timeFrame: Up to 1 year
measure: Overall survival (OS)
timeFrame: Up to 1 year
measure: Incidence of adverse events
timeFrame: Up to 1 year after completion of study treatment
measure: Changes in mood state as measured by Center for Epidemiologic Studies Depression Scale (CES-D
timeFrame: Baseline to up to 6 months
Other outcomes:
measure: "Changes in immune response, measured by serum levels of IL-6
timeFrame: Baseline to up to 6 months
measure: Changes in immune response, measured by serum levels of IL-8
timeFrame: Baseline to up to 6 months
measure: Changes in immune response, measured by serum levels of VEGF
timeFrame: Baseline to up to 6 months
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Houston
country: United States
facility: Lyndon Baines Johnson General Hospital
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: The Woman's Hospital of Texas
state: Texas
city: Houston
country: United States
facility: MD Anderson in Katy
state: Texas
city: Sugar Land
country: United States
facility: MD Anderson in Sugar Land
state: Texas
city: The Woodlands
country: United States
facility: MD Anderson in The Woodlands
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Lois M Ramondetta
role: PRINCIPAL_INVESTIGATOR
References: