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Propranolol Hydrochloride and Chemotherapy in Treating Patients With Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01504126
Recruitment Status : Completed
First Posted : January 5, 2012
Last Update Posted : August 29, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Sprint for Life
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 Drug: Chemotherapy Drug: Propranolol Hydrochloride Other: Quality-of-Life Assessment Procedure: Therapeutic Conventional Surgery Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Feasibility Study: Therapeutic Targeting of Stress Factors in Ovarian Cancer Patients
Actual Study Start Date : March 9, 2012
Actual Primary Completion Date : August 15, 2019
Actual Study Completion Date : August 15, 2019


Arm Intervention/treatment
Experimental: Treatment (propranolol hydrochloride)
Patients receive propranolol hydrochloride PO 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.
Drug: Chemotherapy
Undergo standard chemotherapy
Other Names:
  • Chemo
  • Chemotherapy (NOS)
  • Chemotherapy, Cancer, General

Drug: Propranolol Hydrochloride
Given PO
Other Names:
  • Inderal
  • Innopran XL

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Procedure: Therapeutic Conventional Surgery
Undergo surgical resection




Primary Outcome Measures :
  1. Proportion of patients who successfully complete 6 cycles of chemotherapy with propranolol hydrochloride [ Time Frame: Up to 6 months ]
    The success rate will be estimated with a 90% credible interval.


Secondary Outcome Measures :
  1. Changes in quality of life as measured by the Functional Assessment of Chronic Illness and Therapy- Ovary (FACT-O) [ Time Frame: Baseline to up to 6 months ]
    Descriptive statistics will be used to summarize measurements at each assessment time, and boxplots and histograms will be used to illustrate the distribution of this outcome at each assessment time. Changes from baseline will be similarly summarized. If these data are approximately normally distributed, or transformable to be approximately normally distributed, mixed repeated measures models and linear contrasts will be used to test for changes over time and associations between these quantities. Highly skewed measures analyzed using nonparametric methods.

  2. Changes in mood state as measured by the Hospital Anxiety and Depression Survey (HADS) [ Time Frame: Baseline to up to 6 months ]
    Descriptive statistics will be used to summarize measurements at each assessment time, and boxplots and histograms will be used to illustrate the distribution of this outcome at each assessment time. Changes from baseline will be similarly summarized. If these data are approximately normally distributed, or transformable to be approximately normally distributed, mixed repeated measures models and linear contrasts will be used to test for changes over time and associations between these quantities. Highly skewed measures analyzed using nonparametric methods.

  3. Progression-free survival (PFS) [ Time Frame: Up to 1 year ]
    PFS will be estimated with the product-limit estimator of Kaplan and Meier illustrated with a Kaplan-Meier plot. Proportional hazards models will be used to examine the association between cytokines and PFS.

  4. Overall survival (OS) [ Time Frame: Up to 1 year ]
    Will be estimated with the product-limit estimator of Kaplan and Meier. Proportional hazards models will be used to examine the association between cytokines and OS.

  5. Incidence of adverse events [ Time Frame: Up to 1 year after completion of study treatment ]
    Adverse events will be tabulated with particular attention to grade 3-4 neutropenia and grade 2+ neurotoxicity. The incidence of each type of adverse event will be estimated with a 95% confidence interval.

  6. Changes in mood state as measured by Center for Epidemiologic Studies Depression Scale (CES-D [ Time Frame: Baseline to up to 6 months ]
    scriptive statistics will be used to summarize measurements at each assessment time, and boxplots and histograms will be used to illustrate the distribution of this outcome at each assessment time. Changes from baseline will be similarly summarized. If these data are approximately normally distributed, or transformable to be approximately normally distributed, mixed repeated measures models and linear contrasts will be used to test for changes over time and associations between these quantities. Highly skewed measures analyzed using nonparametric methods.


Other Outcome Measures:
  1. "Changes in immune response, measured by serum levels of IL-6 [ Time Frame: Baseline to up to 6 months ]
    Descriptive statistics will be used to summarize measurements at each assessment time, and boxplots and histograms will be used to illustrate the distribution of this outcome at each assessment time. Changes from baseline will be similarly summarized. If these data are approximately normally distributed, or transformable to be approximately normally distributed, mixed repeated measures models and linear contrasts will be used to test for changes over time and associations between these quantities. Highly skewed measures analyzed using nonparametric methods.

  2. Changes in immune response, measured by serum levels of IL-8 [ Time Frame: Baseline to up to 6 months ]
    Descriptive statistics will be used to summarize measurements at each assessment time, and box-plots and histograms will be used to illustrate the distribution of this outcome at each assessment time. Changes from baseline will be similarly summarized. If these data are approximately normally distributed, or transformable to be approximately normally distributed, mixed repeated measures models and linear contrasts will be used to test for changes over time and associations between these quantities. Highly skewed measures analyzed using non-parametric methods.

  3. Changes in immune response, measured by serum levels of VEGF [ Time Frame: Baseline to up to 6 months ]
    Descriptive statistics will be used to summarize measurements at each assessment time, and boxplots and histograms will be used to illustrate the distribution of this outcome at each assessment time. Changes from baseline will be similarly summarized. If these data are approximately normally distributed, or transformable to be approximately normally distributed, mixed repeated measures models and linear contrasts will be used to test for changes over time and associations between these quantities. Highly skewed measures analyzed using non-parametric methods.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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"

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01504126


Locations
Layout table for location information
United States, Arizona
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States, 85234
United States, Texas
Lyndon Baines Johnson General Hospital
Houston, Texas, United States, 77026-1967
M D Anderson Cancer Center
Houston, Texas, United States, 77030
The Woman's Hospital of Texas
Houston, Texas, United States, 77054
MD Anderson in Katy
Houston, Texas, United States, 77094
MD Anderson in Sugar Land
Sugar Land, Texas, United States, 77478
MD Anderson in The Woodlands
The Woodlands, Texas, United States, 77384
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Sprint for Life
Investigators
Layout table for investigator information
Principal Investigator: Lois M Ramondetta M.D. Anderson Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01504126    
Other Study ID Numbers: 2011-0800
NCI-2012-00056 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2011-0800 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: January 5, 2012    Key Record Dates
Last Update Posted: August 29, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Adenocarcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Cystadenocarcinoma, Serous
Carcinoma, Endometrioid
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Adenocarcinoma, Clear Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Neoplasms, Cystic, Mucinous, and Serous
Endometrial Neoplasms
Uterine Neoplasms