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

August 27, 2019 updated by: M.D. Anderson Cancer Center

Feasibility Study: Therapeutic Targeting of Stress Factors in Ovarian Cancer Patients

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner MD Anderson Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
      • Houston, Texas, United States, 77026-1967
        • Lyndon Baines Johnson General Hospital
      • Houston, Texas, United States, 77054
        • The Woman's Hospital of Texas
      • Houston, Texas, United States, 77094
        • MD Anderson in Katy
      • Sugar Land, Texas, United States, 77478
        • MD Anderson in Sugar Land
      • The Woodlands, Texas, United States, 77384
        • MD Anderson in The Woodlands

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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"

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Therapeutic Conventional Surgery
Undergo surgical resection
Drug: Chemotherapy
Undergo standard chemotherapy
Other Names:
  • Chemo
  • Chemotherapy (NOS)
  • Chemotherapy, Cancer, General
Drug: Propranolol Hydrochloride
Given PO
Other Names:
  • Inderal
  • Innopran XL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to up to 6 months
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.
Baseline to up to 6 months
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.
Up to 1 year
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.
Up to 1 year
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.
Up to 1 year after completion of study treatment
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.
Baseline to up to 6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
"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.
Baseline to up to 6 months
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.
Baseline to up to 6 months
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.
Baseline to up to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)
Sprint for Life

Investigators

  • Principal Investigator: Lois M Ramondetta, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 9, 2012

Primary Completion (Actual)

August 15, 2019

Study Completion (Actual)

August 15, 2019

Study Registration Dates

First Submitted

January 3, 2012

First Submitted That Met QC Criteria

January 4, 2012

First Posted (Estimate)

January 5, 2012

Study Record Updates

Last Update Posted (Actual)

August 29, 2019

Last Update Submitted That Met QC Criteria

August 27, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011-0800 (Other Identifier: M D Anderson Cancer Center)
  • P30CA016672 (U.S. NIH Grant/Contract)
  • NCI-2012-00056 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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