A Pilot Study of BXCL701 in Patients With Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT04123574
• Recruitment Status: Withdrawn
• First Posted: October 11, 2019
• Last Update Posted: February 24, 2022
• Sponsor: BioXcel Therapeutics Inc
• Collaborator: IQVIA Biotech
• Information provided by (Responsible Party): BioXcel Therapeutics Inc

Study Description

Brief Summary:

A study to assess the biochemical and immunomodulatory effects of BXCL701 in pancreatic cancer.

Condition or disease	Intervention/treatment	Phase
Cancer of Pancreas; Cancer of the Pancreas; Neoplasms, Pancreatic; Pancreas Cancer; Pancreatic Cancer	Drug: Talabostat Mesylate	Early Phase 1

Detailed Description:

This is a Phase 0 or "window of opportunity" study where paired specimen analysis, taken before and after drug exposure, will permit the evaluation of target modulation and assessment of immune effector cell infiltration into the tumor and the generation of relevant immune cytokines.

In this study, BXCL701 will be administered at a dose of 0.3 mg, twice daily for a total daily dose of 0.6mg (the previously defined maximum tolerated dose [MTD] of the drug), to all patients for a short period of 14 days. This study is designed to assess the biochemical and immunomodulatory effects of BXCL701 in pancreatic cancer.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Proof of Mechanism Study of BXCL701, a Small Molecule Inhibitor of Dipeptidyl Peptidases (DPPs), in Patients With Pancreatic Cancer
• Estimated Study Start Date: October 15, 2019
• Estimated Primary Completion Date: December 6, 2021
• Estimated Study Completion Date: December 6, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: Single Arm; BXCL701 will be administered for one week at a dose of 0.2 mg, twice daily (BID). If BXCL701 is well-tolerated after the first week of treatment, the dose will be increased to 0.3mg BID for a total daily dose of 0.6mg to all patients for the second week of treatment.

Drug: Talabostat Mesylate; BXCL701 tablets dosage strengths include 0.2mg and 0.05mg tablets for oral administration. Patients are to self-administer the prescribed number of BXCL701 tablets for a total daily dose of 0.6 mg. BXCL701 should not be taken on an empty stomach. Daily blood pressure monitoring will be performed during the dosing period. Administration of at least 1L of intravenous (IV) fluids is required on Day 1. On days when pharmacokinetic (PK) assessments are being performed, BXCL701 should be administered at the study center and should be administered at (approximately) the same time of day on each treatment day.; Other Name: BXCL701

Outcome Measures

Primary Outcome Measures :

1. To characterize the quantitative and qualitative effects of BXCL701 on relevant immune effector cytokines and various immunological effector cells that are consistent with its known mechanism of action. [ Time Frame: Up to 37 days post treatment ]
   To measure how BXCL701 effects the tumor by measuring the rate of tumor cell death or the reduction of tumor cell growth. This will be measured by scans and blood work.

Secondary Outcome Measures :

1. Evaluate the tolerability of exposure to BXCL701: National Cancer Institute Common Terminology Criteria [ Time Frame: Up to 37 days post treatment ]
   assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events
2. Evaluate the effect of exposure to BCXL701 on cancer cell death [ Time Frame: Up to 37days post treatment ]
   Measure the rate of cancer cell death measured by histological staining methods of post-treatment biopsied tissue.
3. Genomic analysis before and after treatment. [ Time Frame: Up to 37 days post treatment ]
   Genomic analysis is the identification, measurement or comparison of genomic features such as DNA sequence, structural variation, gene expression, or regulatory and functional element annotation at a genomic scale.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Has untreated (eg, no prior investigational therapies, chemotherapy, or radiation therapy), locally advanced or metastatic adenocarcinoma of the head, neck, uncinate process, or tail of the pancreas with a local or metastatic lesion that is amenable to biopsy before and after treatment. (Whenever possible, the before and after treatment biopsies should be from the same lesion.)
2. Is able and willing to undergo tumor biopsy before and after treatment. (A pretreatment biopsy may not be needed if tissue is available from a biopsy conducted within 28 days prior to screening that is adequate for the study assessments.)
3. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
4. Is 18 to 75 years of age, inclusive
5. Has adequate organ function within 28 days of treatment initiation
6. For participants with exposure to prior agents associated with decreased left ventricular ejection fraction (LVEF) (e.g. anthracyclines), or if clinically warranted, a documented LVEF > 45% using a standard echocardiogram (ECHO) or multigated acquisition (MUGA) scan test at Screening or within 60 days prior to Cycle 1 Day 1. ECHO or MUGA testing for other participants without relevant medical history or clinical symptoms can be performed if feasible.
7. Has oxygen saturation ≥ 92% on room air.
8. Is able to take an oral medication.
9. Has signed an Informed Consent Form (ICF) prior to the initiation of any study-specific procedures or treatment.
10. Is willing and able to adhere to the study visit schedule and other protocol requirements.
11. Women of childbearing potential (WOCBP) must have a negative pregnancy test at baseline. A woman must be menopausal for at least 12 months before she is considered not to be of reproductive potential.
12. Male and female patients of reproductive potential must agree to use an effective contraceptive method during participation in this study and for 6 months following the study.

Exclusion Criteria:

1. A female who is pregnant or breast-feeding.
2. Has other concurrent malignancies except for basal and squamous cell cancers of the skin and in-situ cervical cancer.
3. Has uncontrolled epilepsy, central nervous system diseases, or a history of mental disorder that is severe enough to hinder the ability of the patient to provide informed consent or that may influence the patient's compliance with the protocol in the judgments of the investigator.
4. Has an upper gastrointestinal obstruction, abnormal physiological function, or malabsorption syndrome that may affect the absorption of study medication.
5. Has required chronic corticosteroids, defined as > 10 mg/day of prednisone or equivalent, or immunosuppressive therapy within the past 3 months. Patient requires treatment with DPP4 inhibitors (e.g. gliptins).
6. Has a premalignant hematologic disorder, eg, myelodysplastic syndrome.
7. Has a severe organ dysfunction or disease that might prevent completion of the treatment regimen, eg, cardiopulmonary diseases (New York Heart Association [NYHA] ≥ Class III, arrhythmia Lown III/IV, global respiratory insufficiency); ascites; acute pancreatitis; bleeding diathesis, coagulopathy, or need for full dose anticoagulation.
8. Has a chronic infectious disease, especially immune deficiency syndromes, eg, human immunodeficiency virus (HIV) infection, active tuberculosis within 12 months prior to potential study participation or suspected/active SARS-CoV-2 (Covid-19) infection.
9. Has a history of severe neurologic disorders, eg, cerebrovascular ischemia within the past year.
10. Has a history of prior deep venous thrombosis or pulmonary embolism within the past year.
11. Has serious medical, psychological, familial, sociological, or geographical conditions or circumstances potentially hampering compliance with the study protocol and follow-up.
12. QT interval corrected for heart rate using Bazett's formula (QTcB) > 440 msec at Screening.
13. Patients with history of symptomatic orthostatic hypotension within 3 months prior to enrollment. Orthostatic hypotension is defined as a drop in systolic blood pressure (BP) of ≥ 20 mmHg or diastolic BP of ≥ 10 mmHg with assumption of an upright posture

Contacts and Locations

Locations

United States, Massachusetts

BioXcel Clinical Research Site

Boston, Massachusetts, United States, 02215

United States, New York

BioXcel Clinical Research Site

New York, New York, United States, 10021

Sponsors and Collaborators

BioXcel Therapeutics Inc

IQVIA Biotech

More Information

• Responsible Party: BioXcel Therapeutics Inc
• ClinicalTrials.gov Identifier: NCT04123574
• Other Study ID Numbers: BXCL701-001
• First Posted: October 11, 2019
• Last Update Posted: February 24, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by BioXcel Therapeutics Inc:

Pancreas; Cancer; Neoplasms; Pancreatic

Additional relevant MeSH terms:

Pancreatic Neoplasms; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases