Official Title: “A Phase II Study of Short-Term Use of Teriparatide (Forteo) in the Treatment of Patients With Postoperative Hypocalcemia”

Primary Objective:

1. To identify the optimal dose of a seven-day course of twice-daily teriparatide as compared to standard therapy for hypocalcemia in patients after total thyroidectomy and/or extensive neck dissections (pharyngectomy, laryngectomy, bilateral paratracheal, mediastinal lymph node neck dissections), with which serum calcium will be raised to corrected serum calcium levels of 8-10.5mg/dL and maintained within this range until the end of the treatment course.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: May 2011

Teriparatide is designed to act like a natural human hormone called parathyroid hormone, which can increase the blood levels of calcium. Calcium plus calcitriol is considered the standard treatment for low calcium in the blood.

If you agree to take part in this study, before surgery, you will have "baseline tests." Blood (about 2 tablespoons) will be drawn to check your blood levels of calcium and vitamin D, as well as liver and kidney functions. This routine blood draw will include a pregnancy test for women who are able to have children. For you to be eligible to take part in this study, the pregnancy test must be negative. You will be asked to collect your urine over 24 hours, to check the calcium level. You will receive a special container with instructions on how to collect your urine. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate). Your medical history will be recorded, including a review of all of your current medications.

After your scheduled surgery, the level of calcium in your blood will be monitored according to the standard of care. Between 18 and 24 hours after the surgery, if your calcium level drops below an acceptable level, or you develop symptoms of low calcium, you will be randomly assigned (as in the toss of a coin) to 1 of 4 groups. One group (the "standard-of-care" group) will receive calcium plus calcitriol alone, for 7 days. The other groups (the "teriparatide" groups) will receive 1 of 3 different dose levels of teriparatide for 7 days, plus calcium and calcitriol for 7 days. There is an equal chance of getting assigned to any of these 4 groups, for the first 40 participants enrolled on this study. If you are enrolled after that point, you have a greater chance of being assigned to the group showing the best results.

STANDARD-OF-CARE GROUP:

If you are assigned to the standard-of-care group, you will receive calcium and calcitriol according to the standard schedule and dose. The calcium will either be given through a vein or by mouth, and calcitriol will be given by mouth.

TERIPARATIDE GROUP:

If you are assigned to a teriparatide group, you will receive teriparatide by an injection under your skin, twice a day for 7 days. You will be taught how to perform the injections yourself, with a pen-sized device. While you are in the hospital, the hospital staff will watch you perform the injections and offer help, if needed. If you are discharged from the hospital and sent home before the 7 days of therapy are complete, you will continue giving yourself the injections (through Day 7) at home. You will receive a User Manual with instructions on self-injections. The medication and pen should remain under refrigeration at 2-8 C (36-46 F). The pen should not be removed from refrigeration for more than 2 -4 hours.

Depending on what dose level of teriparatide you are assigned to receive, you may have to give yourself up to 3 injections each time. In addition to teriparatide, you will receive calcium and calcitriol, according to the standard schedule and dose. The calcium will either be given through a vein or by mouth, and calcitriol will be given by mouth.

BOTH GROUPS:

If your blood calcium level has not returned to normal after the 7 days of treatment, you may need to continue receiving calcium and/or calcitriol for as long as the doctor decides it is necessary.

You will be asked to keep a medication log (diary) of when you take the teriparatide and/or calcium/calcitriol. The log should be returned to the research nurse on Day 8.

On Days 1-7, blood will be drawn to check the level of calcium twice a day (while in the hospital) or once a day (while treated as an outpatient). These blood draws (about 1 teaspoon each time) will be performed 2 hours before receiving teriparatide and/or calcium/calcitriol. If you are discharged home before the 7 days of study treatment are complete, it is your choice whether to have these daily blood draws performed at M. D.

Anderson or a local hospital. If you have the blood drawn at a local hospital, the blood test results will need to be faxed to M. D. Anderson each day.

Blood will also be drawn to check your calcium and parathyroid hormone levels after the study treatment is over. The first of these blood draws (about 1 tablespoon each time) will be performed at 3 days after receiving your last dose of teriparatide and/or your last dose of calcium/calcitriol. The second blood draw will be performed at 4 weeks after the surgery.

Starting on Day 7, and again at 4 weeks after surgery, you will be asked to collect your urine over the course of a 24-hour period. This is so the level of calcium in your urine can be measured. You will receive special containers with instructions on how to collect your urine.

From Day 1 to Day 7, if you are discharged from the hospital and sent home, the study personnel will call you on the phone once a day to see how you are doing. At 3 days after receiving your last dose of teriparatide and/or your last dose of calcium/calcitriol, and at 4 weeks after the surgery, you will be called again to see how you are doing.

If intolerable side effects occur while you are receiving study treatment, call the study doctor or the study nurse. The teriparatide doses may be stopped. If the teriparatide is stopped for any reason, you will be asked to have blood (about 1 teaspoon) drawn for routine tests within 24 hours.

After the urine collection, blood draw, and phone call at 4 weeks after the surgery, your participation in this study will be over.

This is an investigational study. Teriparatide is FDA-approved for the treatment of osteoporosis (when bones become weaker and have a high risk for breaking) as a once-a-day injection under the skin. However, its use for low calcium levels after head and neck surgery is experimental. For this purpose, it has been authorized for use in research only.

The pen-shaped device that is used to inject the teriparatide is FDA-approved. Teriparatide will be provided free of charge during this study. There is also no cost to you for the pen device that is used to inject the teriparatide. You and/or your insurance provider will be responsible for the costs of the calcium and calcitriol. Up to 500 patients will be screened for this study, but only up to 150 study participants will be enrolled and receive treatment on this study. All will be enrolled at M. D. Anderson.

Intervention(s) in this Clinical Trial

• Drug: Teriparatide
  • Subcutaneous Injection Every 12 Hours for 7 Days
• Drug: Calcium
  • 1000 milligrams PO Every 12 Hours
• Drug: Calcitriol
  • 0.25 micrograms PO Every 12 Hours

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Calcium + Calcitriol
• Experimental: 2
  • Teriparatide at 20 mcg + Calcium + Calcitriol
• Experimental: 3
  • Teriparatide at 40 mcg + Calcium + Calcitriol
• Experimental: 4
  • Teriparatide at 60 mcg + Calcium + Calcitriol

Primary Measures

• The goal of this clinical research study is to see if Forteo (teriparatide) can help return the calcium level in the blood to normal if it becomes low after certain types of surgery.
  • Time Frame: 3 Years
    Safety Issue?: No

Secondary Measures

• The safety of teriparatide in treating low blood calcium levels will also be studied.
  • Time Frame: 3 Years
    Safety Issue?: Yes

Inclusion Criteria:

• Patients who are scheduled for total thyroidectomy, pharyngectomy, laryngectomy, bilateral paratracheal and/or mediastinal lymph node neck dissections.
• Patients who develop, between 18-24 hours after surgery, hypocalcemia as defined by a corrected serum calcium <8.0mg/dL. [Corrected serum calcium (mg/dL) = Measured calcium
• + (4-albumin) x 0.8]

Exclusion Criteria:

• Patients who have jejunal tubes
• Patients <18 years old.
• Treatment with teriparatide or calcitriol (Rocaltrol) within 1 month prior to surgery
• Treatment with a bisphosphonate within 3 months prior to surgery
• Hypercalcemia (corrected serum calcium >10.5mg/dL) or hypocalcemia (corrected serum calcium <8.4mg/dL) on preoperative labs (drawn within 21 days of surgery)
• Paget's disease of bone
• Elevated alkaline phosphatase > institutional upper limit of normal (ULN)
• History of external beam irradiation to the skeleton
• History of skeletal metastases
• History of untreated gout
• History of unstable angina pectoris
• History of symptomatic orthostatic hypotension
• Pregnancy (as screened by a serum/urine pregnancy test) or breast-feeding. Female subjects of childbearing potential must have a negative pregnancy test within 7 days of surgery. Postmenopausal women (absence of menses for 12 months) or women with history of hysterectomy or bilateral oophorectomy will not be required to have a pregnancy test. Male and female patients of reproductive potential must agree to utilize an effective form of contraception throughout the study period. The definition of effective contraception will be based on the judgment of the Investigator or designated associate.
• Hepatic and renal dysfunction defined by the following parameters: (a) Serum AST (SGOT) and ALT (SGPT) > 3 times the institutional ULN, (b) Total serum bilirubin > 2 times the institutional ULN, (c) Serum creatinine > 1.5mg/dL or estimated creatinine clearance < 40mL/min
• Psychiatric illness or social situation that would limit compliance with study requirements
• Concomitant use of digoxin
• Patients may not be receiving any other investigational agents or have participated in any investigational drug study within 28 days preceding the start of study treatment.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: M.D. Anderson Cancer Center

Overall Clinical Trial Officials and Contacts

Mimi Hu, MD Principal Investigator U.T.M.D. Anderson Cancer Center  

Overall Contact: Mimi Hu, MD 713-792-2841 

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00623974

Study ID Number: 2006-0562

ClinicalTrials.gov Identifier: NCT00623974

Health Authority: United States: Food and Drug Administration