MDACC Study Summary 2008-0647

Study Summary
No. 2008-0647:.......Endocrine; Gastrointestine; Neural......Alexandria T. Phan......Gastrointestinal Medical Oncology

Study Summary Title



Study Summary Number:	2008-0647

Study Title:	A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Ascending, Multi-dose Study to Determine the Safety and Tolerability of Orally Administered LX1606 in Subjects with Symptomatic Carcinoid Syndrome Refractory to Stable-dose Octreotide Long-acting Release Depot Therapy (LX1606.1-202-CS)

Physician

New Patient Referral



Name:	Alexandria T. Phan	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Gastrointestinal Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2828 Contact us about clinical trials

General Information



Disease Group:	Endocrine Gastrointestine Neural	Supported By:	Lexicon Pharmaceuticals, Inc.

Phase of Study:	Phase II	Return Visit:	Every week.

Treatment Agents:	LX1606	Home Care:	NA

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	NA


Description/ Intervention:	The goal of this clinical research study is to learn about the safety of giving LX1606 to patients with carcinoid syndrome. Four different dose levels of LX1606 will be tested in order to learn if and how LX1606 at different dose levels may affect the symptoms of carcinoid syndrome. The symptoms may include flushing, abdominal pain, and diarrhea.

Study Objectives / Outcomes

Primary
· To evaluate the safety and tolerability of orally administered LX1606 in subjects with symptomatic carcinoid syndrome.

Secondary
· To assess the effects of four doses of LX1606 (150 mg three times daily [tid], 250 mg tid, 350 mg tid, and 500 mg tid) by measuring symptomatic response over time versus baseline, as determined by number of daily bowel movements

· To assess the effects of a range of multiple oral doses of LX1606 in subjects with carcinoid syndrome by evaluating:
- Change in stool form
- Change in the sensation of urgency to defecate
- Change in subjective global assessment of symptoms associated with carcinoid syndrome
- Change in subjective assessment of abdominal pain or discomfort

· To assess the effects of a range of multiple doses of LX1606 on Chromagranin-A (CgA) levels in blood

· To evaluate any effects of a range of multiple doses of LX1606 on cutaneous flushing episodes

· To evaluate any effects of a range of multiple doses of LX1606 on the frequency of rescue, short-acting octreotide dosing

· To assess the concentrations of LX1606 and its active moiety, LP-778902, in plasma over a range of multiple oral doses in subjects with symptomatic carcinoid syndrome

· To assess the pharmacodynamic effects of LX1606 over a range of multiple oral doses by assessing 5-HT levels in blood over time versus baseline

· To assess the pharmacodynamic effects of LX1606 over a range of multiple oral doses by assessing 5-HIAA levels in urine over time versus baseline

Study Status Information



Study Activation / Registration Date:	06/30/2009

IRB Review and Approval Date:	05/01/2009

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Closed

Projected Accrual:	24

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Age 18 years or older at the time of screening.

2) Male or female; males and females of childbearing potential must agree to use an adequate method of contraception during the study and for 30 days after the last follow-up visit.

3) Biopsy-proven metastatic carcinoid tumor with disease extent confirmed by computed tomography (CT), magnetic resonance imaging (MRI), or radionuclide imaging.

4) Refractory to octreotide therapy, defined as experiencing >/= 4 bowel movements per day despite stable-dose octreotide LAR depot therapy (and supplemental rescue, short-acting octreotide therapy, as needed). For the purposes of this study, stable-dose octreotide therapy is defined as octreotide LAR depot therapy or a continuous subcutaneous infusion of octreotide therapy via pump at the same dose level for at least 3 months prior to the Run-In Period. Confirmation of eligibility will be determined by mean number of bowel movements measured during the Run-In Period.

5) Ability and willingness to provide written informed consent prior to participation in any study-related activities and to participate in and comply with the study requirements.

Exclusion Criteria:

1) More than 12, high-volume, watery bowel movements per day associated with a clinical syndrome of volume contraction, dehydration, or hypotension compatible with a "pancreatic cholera"-type clinical syndrome.

2) Karnofsky Performance Status =/< 70%.

3) Clinical laboratory values for hematology (at Screening): a. Absolute neutrophil count (ANC) =/< 1500 cells/mm^3; or b. Platelets =/< 100,000 cells/mm^3; or c. Hemoglobin (Hgb) =/< 9 g/dL.

4) Liver function test levels (at Screening) such that: a. AST (SGOT), ALT (SGPT) =/> 2 x ULN;or b. Total bilirubin outside the upper limits of normal range; or c. ALP =/> 1.5 x ULN; or d. Serum creatinine =/> 1.5 x ULN.

5) Any other clinically significant laboratory abnormality at screening.

6) Any clinically significant abnormalities on resting ECG (relative to patient population).

7) Surgery within 60 days prior to Day -28 of the Run-In Period.

8) A history of short bowel syndrome (SBS).

9) Concomitant use of antidiarrheal agents such as loperamide, diphenoxylate, bismuth subsalicylate, paregoric, etc. (with the exception of bulking agents), anticholinergic antidepressants, opioid analgesic drugs, or drugs (prescription, over-the-counter (OTC), or herbal) specifically affecting bowel motility during the Run-In Period and for the duration of the study unless if, in the opinion of the Investigator: a. Discontinuation of such medications places the subject at unnecessary health risk; and

10) (continuation of #9) b.Use of these concomitant medications has been stable for at least three months prior to Day -28 of the Run-In Period (defined as a regimen without significant change within the three months preceding Run-In).

11) History of positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), human immunodeficiency virus (HIV) 1, or HIV 2.

12) Pregnant or nursing (lactating) women.

13) Positive pregnancy test at Screening or baseline

14) A history of bleeding diathesis.

15) Life expectancy <12 months.

16) Presence of any clinically significant findings at Screening medical history or physical examination (relative to patient population) that, in the Investigator's or Sponsor's opinion, would compromise the outcome of the study.

17) A history of, or the existence of, any surgical or medical condition that, in the judgment of the Investigator, might interfere with the absorption, distribution, metabolism, or excretion of LX1606.

18) Any concurrent conditions that could interfere with the safety and/or tolerability measurements.

19) A history of substance or alcohol abuse within 2 years prior to screening.

20) Participation in any other investigational drug study within 30 days prior to Day -28 of the Run-In Period

21) Administration of any investigational agent within 30 days of Day -28 of the Run-In Period or any therapeutic protein or antibody within 90 days of Day -28 of the Run-In Period

22) Previous exposure to a tryptophan hydroxylase (TPH) inhibitor.

Links

Registration Number: NCT00853047
Study Information on Clinical Trials Registry (clinicaltrials.gov)