Tolvaptan in Hyponatremic Cancer Patients

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01199198
• Collaborator: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Enrollment: 52
• Location: 1
• Arms: 2
• Duration (Months): 28.1
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Advanced Cancers	Drug: Tolvaptan; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Randomized Placebo-Controlled Trial of Tolvaptan in Hyponatremic Patients With Cancer
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: Sugar Pill

Outcome Measures

Primary Outcome Measures

1. Participants Whose Serum Sodium Concentration Corrected to at Least 135 mEq/L on Day 14 [14 days]

   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). Proportion of participants whose serum sodium concentration is corrected to at least 136 mEq/Lon day14.

Secondary Outcome Measures

1. Length of Stay in Hospital [From administration of treatment to time of discharge]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UT MD Anderson Cancer Center website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01199198
• Other Study ID Numbers: 2009-0862
• First Posted: Sep 10, 2010
• Last Update Posted: Sep 23, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by M.D. Anderson Cancer Center: Hyponatremia; Serum sodium; Tolvaptan; Placebo
• Additional relevant MeSH terms: Tolvaptan

Study Results

Participant Flow

Recruitment Details	Recruitment Period: May 5, 2011 to July 13, 2012. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.
Pre-assignment Detail	Of the 52 participants enrolled, only 48 patients were randomized to participate in the study. Two participants were not randomized due to contra indicated medication and another two were not randomized due to exclusion criteria. The study was stopped for superiority.

Arm/Group Title	Tolvaptan Group	Placebo Group
Arm/Group Description	Starting dose 15 mg orally once a day for 14 days.	Placebo orally once a day for 14 days.
Period Title: Overall Study
STARTED	24	24
COMPLETED	17	13
NOT COMPLETED	7	11

Baseline Characteristics

Arm/Group Title	Tolvaptan Group	Placebo Group	Total
Arm/Group Description	Starting dose 15 mg orally once a day for 14 days.	Placebo orally once a day for 14 days.	Total of all reporting groups
Overall Participants	17	13	30
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60	69	65
Sex: Female, Male (Count of Participants)
Female	8 47.1%	6 46.2%	14 46.7%
Male	9 52.9%	7 53.8%	16 53.3%
Region of Enrollment (participants) [Number]
United States	17 100%	13 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Participants Whose Serum Sodium Concentration Corrected to at Least 135 mEq/L on Day 14
Description	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). Proportion of participants whose serum sodium concentration is corrected to at least 136 mEq/Lon day14.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

"Evaluable participants" are defined as all participants excluding those who drop out of the study due to non-study related reasons. Participants who are lost to follow-up for unknown or study related reasons will be counted as failures based on the intent to treat principal.

Arm/Group Title	Tolvaptan Group	Placebo Group
Arm/Group Description	Starting dose 15 mg orally once a day for 14 days.	Placebo orally once a day for 14 days.
Measure Participants	17	13
Number [participants]	16 94.1%	1 7.7%

2. Secondary Outcome

Title	Length of Stay in Hospital
Time Frame	From administration of treatment to time of discharge

Outcome Measure Data

Analysis Population Description

"Evaluable participants" are defined as all participants excluding those who drop out of the study due to non-study related reasons. Participants who are lost to follow-up for unknown or study related reasons will be counted as failures based on the intent to treat principal.

Arm/Group Title	Tolvaptan Group	Placebo Group
Arm/Group Description	Starting dose 15 mg orally once a day for 14 days.	Placebo orally once a day for 14 days.
Measure Participants	17	13
Mean (Standard Deviation) [days]	21 (15)	26 (15)

Adverse Events

Time Frame	Adverse event collection through follow up, anticipated Day 30 +/- 5 days. Overall collection period: May 10, 2011 to August 24, 2012.
Arm/Group Title	Tolvaptan Group		Placebo Group
Arm/Group Description	Starting dose 15 mg orally once a day for 14 days.		Placebo orally once a day for 14 days.
All Cause Mortality
	Tolvaptan Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/13 (0%)
Serious Adverse Events
	Tolvaptan Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/17 (100%)		0/13 (0%)
Gastrointestinal disorders
Nausea	2/17 (11.8%)		0/13 (0%)
General disorders
Pain	17/17 (100%)		0/13 (0%)
Hypotension	8/17 (47.1%)		0/13 (0%)
Worsening of Edema	3/17 (17.6%)		0/13 (0%)
Infections and infestations
Infections (any type)	13/17 (76.5%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	0/17 (0%)		0/13 (0%)
Skin and subcutaneous tissue disorders
Edema	17/17 (100%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Tolvaptan Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/13 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.