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Telotristat Ethyl to Promote Weight Stability in Patients With Advanced Stage Pancreatic Cancer

Primary Purpose

Locally Advanced Unresectable Pancreatic Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma, Recurrent Pancreatic Adenocarcinoma

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Gemcitabine

Nab-paclitaxel

Telotristat Ethyl

About this trial

This is an interventional supportive care trial for Locally Advanced Unresectable Pancreatic Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

GROUP 1 (Telotristat ethyl treatment group): Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
GROUP 1 (Telotristat ethyl treatment group): Weight loss of 10% or more.
GROUP 1 (Telotristat ethyl treatment group): Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 14 days prior to registration.
GROUP 1 (Telotristat ethyl treatment group): Histologic or cytological diagnosis of recurrent or metastatic pancreas adenocarcinoma (PDAC) who present for first line chemotherapy treatment for metastatic disease.
GROUP 1 (Telotristat ethyl treatment group): Advanced stage pancreas cancer (recurrent/metastatic).
GROUP 1 (Telotristat ethyl treatment group): Measurable disease determined using guidelines of Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Baseline tumor assessment should be performed using high resolution computed tomography (CT) scans or magnetic resonance imaging (MRI).
GROUP 1 (Telotristat ethyl treatment group): Prior systemic therapy (adjuvant or neoadjuvant setting are acceptable) if disease progressed or recurred within at least 3 months after treatment.
GROUP 1 (Telotristat ethyl treatment group): Estimated life expectancy of > 12 weeks, as assessed by the site investigator.
GROUP 1 (Telotristat ethyl treatment group): If sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods) due to unknown risk of teratogenicity.
GROUP 1 (Telotristat ethyl treatment group): Hemoglobin ≥ 8 g/dL (obtained within 7 days prior to registration).
GROUP 1 (Telotristat ethyl treatment group): Absolute Neutrophil Count (ANC) ≥ 1,500/mm³ (obtained within 7 days prior to registration).
GROUP 1 (Telotristat ethyl treatment group): Platelet Count (PLT) ≥ 100,000/mm³ (obtained within 7 days prior to registration).
GROUP 1 (Telotristat ethyl treatment group): Creatinine ≤ 1.5 mg/dL (obtained within 7 days prior to registration).
GROUP 1 (Telotristat ethyl treatment group): Albumin ≥ 2 g/dL (obtained within 7 days prior to registration).
GROUP 1 (Telotristat ethyl treatment group): Bilirubin ≤ 1.5 mg/dL (obtained within 7 days prior to registration).
GROUP 1 (Telotristat ethyl treatment group): Aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) or < 5 x ULN in the setting of liver metastases (obtained within 7 days prior to registration).
GROUP 1 (Telotristat ethyl treatment group): Alanine aminotransferase (ALT) ≤ 3 x ULN or < 5 x ULN in the setting of liver metastases (obtained within 7 days prior to registration).
GROUP 1 (Telotristat ethyl treatment group): Prior radiation is allowed if happened more than 2 weeks of enrollment.
GROUP 2 (Non-Telotristat ethyl group): Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
GROUP 2 (Non-Telotristat ethyl group): Stable weight or loss of < 10% by history.
GROUP 2 (Non-Telotristat ethyl group): ECOG Performance Status of 0-2 within 14 days prior to registration.
GROUP 2 (Non-Telotristat ethyl group): Histologic or cytological diagnosis of locally advanced unresectable, recurrent/metastatic PDAC who present for first line chemotherapy treatment for metastatic disease.
GROUP 2 (Non-Telotristat ethyl group): Advanced stage PDAC (locally advanced unresectable/recurrent/metastatic).
GROUP 2 (Non-Telotristat ethyl group): Prior systemic therapy (adjuvant or neoadjuvant setting are acceptable) if disease progressed or recurred within at least 3 months after treatment.
GROUP 2 (Non-Telotristat ethyl group): Estimated life expectancy of > 12 weeks, as assessed by the site investigator.
GROUP 2 (Non-Telotristat ethyl group): Prior radiation is allowed if happened more than 2 weeks of enrollment.

Exclusion Criteria:

GROUP 1 (Telotristat ethyl treatment group): Subjects with histology other than adenocarcinoma. Examples include: neuroendocrine tumors, acinar cell cancer, sarcoma or lymphoma of the pancreas.
GROUP 1 (Telotristat ethyl treatment group): Ongoing or active infection.
GROUP 1 (Telotristat ethyl treatment group): Symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia. Symptomatic heart failure (New York Heart Association [NYHA] Class II-IV).
GROUP 1 (Telotristat ethyl treatment group): Acute or sub-acute intestinal obstruction.
GROUP 1 (Telotristat ethyl treatment group): Ascites.
GROUP 1 (Telotristat ethyl treatment group): Documented and/or symptomatic or known brain or leptomeningeal metastases.
GROUP 1 (Telotristat ethyl treatment group): Severely immune-compromised (other than being on steroids) including known human immunodeficiency virus (HIV) infection.
GROUP 1 (Telotristat ethyl treatment group): Concurrent active malignancy, other than adequately treated non-melanoma skin cancer, other noninvasive carcinoma, or in situ neoplasm. A subject with previous history of malignancy is eligible if he/she has been disease-free for > 3 years.
GROUP 1 (Telotristat ethyl treatment group): Breast-feeding or pregnant. Serum pregnancy test for women of child-bearing potential must be performed within 7 days prior to first dose of study treatment.
GROUP 1 (Telotristat ethyl treatment group): Prior autologous or allogeneic organ or tissue transplantation.
GROUP 1 (Telotristat ethyl treatment group): Known allergy to any of the treatment components.
GROUP 1 (Telotristat ethyl treatment group): Have any condition that does not permit compliance with the study schedule including psychological, geographical, or medical.
GROUP 1 (Telotristat ethyl treatment group): Not able to swallow. Inability to take oral medications.
GROUP 1 (Telotristat ethyl treatment group): Patients with chronic constipation.
GROUP 2 (Non-Telotristat ethyl group): Subjects with histology other than adenocarcinoma. Examples include: neuroendocrine tumors, acinar cell cancer, sarcoma or lymphoma of the pancreas.
GROUP 2 (Non-Telotristat ethyl group): Ongoing or active infection.
GROUP 2 (Non-Telotristat ethyl group): Symptomatic congestive heart failure, unstable angina or arrhythmia. Symptomatic heart failure (NYHA Class II-IV).
GROUP 2 (Non-Telotristat ethyl group): Acute or sub-acute intestinal obstruction.
GROUP 2 (Non-Telotristat ethyl group): Severely immune-compromised (other than being on steroids) including known HIV infection.

Sites / Locations

Emory University Hospital Midtown
Emory University Hospital/Winship Cancer Institute
Emory Saint Joseph's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Group 1 (gemcitabine/nab-paclitaxel and telotristat ethyl)

Group 2 (gemcitabine/nab-paclitaxel)

Arm Description

Patients receive gemcitabine/nab-paclitaxel combination chemotherapy on days 1, 8 and 15, and telotristat ethyl PO QD, BID, or TID on days 1 and 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive gemcitabine/nab-paclitaxel chemotherapy (at the discretion of the investigator) on days 1, 8 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Weight stability

Weight stability will be documented as percent weight change at 3 months compared to baseline.

Secondary Outcome Measures

Change in serum 5-hydroxyindoleacetic acid (5-HIAA) levels

The change will be summarized as mean and standard deviation.

Change in 24-hr urine 5-hydroxyindoleacetic acid (5-HIAA) levels

The change will be summarized as mean and standard deviation.

Mid arm circumference (MAC) measured in inches

Mid arm circumference (MAC) will be reviewed on cross sectional imaging and will be assessed with imaging guided measurements of the psoas and rectus abdominis muscle.

Quality of life (QOL)

Quality of life (QOL) will be assessed by the Obesity Related Quality of Life (OWL-QOL)-17 questionnaire.

Blood serotonin levels

Blood serotonin levels will be compared in the 2 groups.

Response rate (RR)

Response rate (RR) will be assessed per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, in patients receiving telotristat ethyl (Group 1).

Median overall survival (MOS)

Median overall survival (MOS) will be measured using the Kaplan-Meier method.

Duration of response

Duration of response will be estimated from time of documentation of response to time of progression and will be evaluated by computed tomography/magnetic resonance imaging scans of the organ(s) with the target lesion(s) based on RECIST criteria.

Full Information

NCT ID

NCT03910387

First Posted

April 9, 2019

Last Updated

August 26, 2023

Sponsor

Emory University

Collaborators

National Cancer Institute (NCI), Lexicon Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03910387

Brief Title

Telotristat Ethyl to Promote Weight Stability in Patients With Advanced Stage Pancreatic Cancer

Official Title

Weight Loss in Patients With Advanced Stage Pancreatic Cancer: Role of Serotonin and Effects of Telotristat Ethyl

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 17, 2019 (Actual)

Primary Completion Date

October 26, 2023 (Anticipated)

Study Completion Date

October 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Emory University

Collaborators

National Cancer Institute (NCI), Lexicon Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This phase II trial studies how well telotristat ethyl works in promoting weight stability in patients with pancreatic adenocarcinoma that has come back and spread to other places in the body. Telotristat ethyl may decrease bowel movements which may make patients gain weight. Stabilizing weight may help patients tolerate chemotherapy better and improve longevity.

Detailed Description

PRIMARY OBJECTIVES: I. Evaluate weight stability after 3 months of telotristat ethyl treatment in patients who have significant weight loss (documented to be more than or equal to 10%) prior to the start of treatment. (Group 1). II. Evaluate the change in serum and 24-hours (hr) urine 5-hydroxyindoleacetic acid (5-HIAA) in patients with locally advanced unresectable, recurrent or metastatic pancreatic adenocarcinoma (PDAC) receiving chemotherapy. (Group 2). SECONDARY OBJECTIVES: I. Evaluate the impact of weight stabilization/gain on patients in Group 1 on performance status, quality of life (QOL), mid arm circumference (MAC) and muscle mass on cross sectional imaging. II. Evaluate correlations between changes in serotonin/ 5HIAA levels on radiologic response, weight stability, mid arm circumference (MAC), and muscle mass on cross sectional imaging. III. Evaluate the relation of baseline serum and 24-hr urine 5-HIAA on weight loss in patients with advanced PDAC. IV. Safety and tolerability of telotristat ethyl with gemcitabine/nab-paclitaxel combination chemotherapy. V. Evaluate response rate (RR) assessed per Response Evaluation Criteria in Solid Tumors (RECIST), progression free survival and overall survival in patients receiving telotristat ethyl (Group 1). OUTLINE: Patients are randomized to 1 of 2 groups. GROUP 1: Patients receive gemcitabine/nab-paclitaxel combination chemotherapy on days 1, 8 and 15, and telotristat ethyl orally (PO) once daily (QD), twice daily (BID), or thrice daily (TID) on days 1 and 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. GROUP 2: Patients receive chemotherapy (at the discretion of the investigator) on days 1, 8 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, then every 8 weeks thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Locally Advanced Unresectable Pancreatic Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma, Recurrent Pancreatic Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Group 1 (gemcitabine/nab-paclitaxel and telotristat ethyl)

Arm Type

Experimental

Arm Description

Arm Title

Group 2 (gemcitabine/nab-paclitaxel)

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

Gemzar, dFdCyd, Difluorodeoxycytidine

Intervention Description

Given gemcitabine/nab-paclitaxel combination therapy

Intervention Type

Drug

Intervention Name(s)

Nab-paclitaxel

Other Intervention Name(s)

ABI-007, Abraxane, Nanoparticle Albumin-bound Paclitaxel

Intervention Description

Given gemcitabine/nab-paclitaxel combination therapy

Intervention Type

Drug

Intervention Name(s)

Telotristat Ethyl

Other Intervention Name(s)

Xermelo

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Weight stability

Description

Weight stability will be documented as percent weight change at 3 months compared to baseline.

Time Frame

Baseline up to 3 months after study start

Secondary Outcome Measure Information:

Title

Change in serum 5-hydroxyindoleacetic acid (5-HIAA) levels

Description

The change will be summarized as mean and standard deviation.

Time Frame

Baseline up to 4 months after study start

Title

Change in 24-hr urine 5-hydroxyindoleacetic acid (5-HIAA) levels

Description

The change will be summarized as mean and standard deviation.

Time Frame

Baseline up to 4 months after study start

Title

Mid arm circumference (MAC) measured in inches

Description

Mid arm circumference (MAC) will be reviewed on cross sectional imaging and will be assessed with imaging guided measurements of the psoas and rectus abdominis muscle.

Time Frame