Tolvaptan in Hyponatremic Cancer Patients

This study has been completed.
Sponsor:
Collaborator:
Otsuka Pharmaceutical Development & Commercialization, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01199198
First received: September 8, 2010
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

The goal of this clinical research study is to learn if tolvaptan can help raise salt (sodium) levels in the cancer patients' blood by removing extra body water as urine.


Condition Intervention Phase
Advanced Cancers
Drug: Tolvaptan
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Randomized Placebo-Controlled Trial of Tolvaptan in Hyponatremic Patients With Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Proportion of Patients whose Serum Sodium Concentration Corrected to at least 135 mEq/L on Day 14 [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    Compare proportion of hyponatremia cancer patients with a normalized serum sodium concentration at day 14 between those treated with Tolvaptan and those treated with a placebo (standard of care).


Enrollment: 52
Study Start Date: May 2011
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tolvaptan Group
Tolvaptan Group: Starting dose 15 mg by mouth once a day for 14 days.
Drug: Tolvaptan
Starting dose 15 mg by mouth once a day for 14 days.
Other Name: Samsca
Placebo Comparator: Placebo Group
Placebo Group: Placebo by mouth once a day for 14 days.
Drug: Placebo
Placebo by mouth once a day for 14 days.
Other Name: Sugar Pill

  Hide Detailed Description

Detailed Description:

The Study Drug:

Tolvaptan is designed to help raise salt levels in your blood by removing extra body water as urine.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. You will have an equal chance of being assigned to either group:

  • If you are in Group 1, you will take tolvaptan and receive standard of care
  • If you are in Group 2, you will take a placebo and receive the standard of care for patients with hyponatremia. A placebo is a tablet that looks like the study drug but has no active ingredients.

You will not know which group you are assigned. However, if needed for your safety, you will be able to find out what you are receiving at any time.

Study Drug Administration:

You will take tolvaptan or the placebo 1 time every day by mouth for 14 days.

If you are receiving the placebo, you will also receive the standard of care for hyponatremia. Examples of the standard of care include limiting your water and fluid intake, or giving you salt tablets and other drugs such as diuretics. Your doctor will describe these in more detail.

You will be given a drug diary to record when you take the study drug/placebo. You will return any unused drug/placebo at the end of 14 days.

You should avoid grapefruit and grapefruit juice while you are taking tolvaptan.

Study Visits:

At every visit, you will be asked if you have had any side effects.

On Days 1, 2, and 3:

  • Blood (about 1 teaspoon) will be drawn for routine tests. On Day 1, this sample will be drawn 2 times.
  • Your weight and vital signs will be measured.
  • The study staff will record how much fluid you are drinking and how much you are urinating.
  • You will be asked about any drugs that you may be taking.
  • If the doctor thinks it is needed, you will have a physical exam.

On Day 7:

  • Your medical history will be reviewed and updated.
  • You will be asked about any drugs that you may be taking.
  • Blood (about 1 teaspoon) will be drawn for routine tests and tests to measure how concentrated your blood results are.
  • Your weight and vital signs will be measured.

On Day 14:

  • Your medical history will be reviewed and updated.
  • Your weight and vital signs will be measured.
  • Blood (about 1 teaspoon) and urine will be collected for routine tests and tests to measure how concentrated your blood and urine are.
  • The study staff will record how much fluid you are drinking and how much you are urinating.
  • You will be asked about any drugs that you may be taking.
  • You will complete the MMSE.

If the doctor thinks it is needed, you will have a physical exam.

Length of Study:

You will take the study drug/placebo for 14 days. You will be taken off study if you have intolerable side effects, if the disease gets worse, or if the study doctor thinks it is in your best interest.

Your participation on the study will be over once you have completed the end-of-study visit.

End-of-Study- Day 30 Follow-up Visit:

At 30 days after the last dose of study drug (or placebo), you will have an end-of-study visit in clinic or by telephone. At this visit, the following tests and procedures will be performed.

  • Your medical history will be reviewed and updated.
  • Blood (about 1 teaspoon) will be drawn for routine tests and tests to measure how concentrated your blood results are.
  • You will be asked about any side effects that you may be having and any drugs that you may be taking.
  • The study staff will record how much fluid you are drinking and how much you are urinating.
  • If the doctor thinks it is needed, you will have a physical exam.

This is an investigational study. Tolvaptan is FDA approved and commercially available to treat hyponatremia (low levels of salt [sodium] in the blood due to too much body water). Its use in patients with cancer who have hyponatremia is investigational.

Up to 170 patients will take part in this study. All will be enrolled at MD Anderson.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Euvolemic or hypervolemic (patients with heart or liver failure) with cancer admitted to MD Anderson Cancer Center for any reasons with serum sodium between 125 and 130 mEq/L (both inclusive)
  2. Patients must be greater than or equal to 18 years of age
  3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 at baseline.
  4. Women of childbearing potential must use a medically accepted method of contraception and to continue use of this method for the duration of the study and for 30 days after study participation. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method. Men must practice abstinence or use a barrier method of birth control, and must agree to continue use for the duration of the study and for 30 days after study participation.
  5. Subjects must be able to comply with scheduled visits and follow-ups.
  6. Informed consent must be signed

Exclusion Criteria:

  1. History of hypersensitivity to tolvaptan
  2. Patients admitted to the critical care unit.
  3. Patients with renal failure(creatinine clearance less than 25 ml/min)
  4. Patients with a life expectancy less than 3 months
  5. Patients with volume depletion, BP < 100/60 or urinary sodium <20 meq/L.
  6. Patients who are not able to swallow or cannot take medication through feeding tubes
  7. Patients with diuretic-induced hyponatremia.
  8. Patients with spurious hyponatremia
  9. Patients with hyponatremia related to psychogenic polydypsia, head trauma, post operative conditions, uncontrolled hypothyroidism or cortisol insufficiency or any hyponatremia associated with the use of medication that can be safely withdrawn.
  10. The use of alcohol while participating in the study
  11. Currently taking demeclocycline, lithium, benzazepine derivatives, ketoconazole, grapefruit, grapefruit juice and receiving strong CYP3A inhibitors such as clarithromycin, fluconazole, voriconazole, posaconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, and telithromycin.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01199198

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Principal Investigator: Abdulla K. Salahudeen, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01199198     History of Changes
Other Study ID Numbers: 2009-0862
Study First Received: September 8, 2010
Last Updated: September 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Hyponatremia
Serum sodium
Tolvaptan
Placebo

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on July 23, 2014