Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma

NCT ID: NCT02352831

Last Updated: 2019-08-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2018-10-19

Brief Summary

There are two parts to this study: the goal of the first part of the study is to find the best dose of tosedostat when given in combination with capecitabine. The goal of the second part of the study is to look at how participants respond to treatment with tosedostat and capecitabine.

Conditions

Pancreatic Cancer; Cancer of Pancreas; Cancer of the Pancreas; Pancreas Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I (tosedostat + capecitabine)

• The phase I study will be conducted in the standard 6-patient-per-cohort dose de-escalation fashion.
• Tosedostat by mouth daily Days 1-21 of each 21-day cycle. Dose Level 0 (starting dose) = 120 mg PO daily and Dose Level -1 = 60 mg PO daily. All 6 patients in the Phase 1 received 120 mg starting dose of tosedostat.
• Capecitabine 1000 mg/m^2 by mouth BID Days 1-14 of each 21-day cycle
• Fresh tissue biopsy: Patients who have a partial response at the end of cycle 2 will be required to undergo biopsy if deemed safe for the patient and tissue is feasible to obtain.

Group Type: EXPERIMENTAL

Tosedostat

Intervention Type: DRUG

Capecitabine

Intervention Type: DRUG

Fresh tissue biopsy

Intervention Type: PROCEDURE

Patients who have a partial response at the end of cycle 2 will be required to undergo biopsy if deemed safe for the patient and tissue is feasible to obtain.

Phase II (tosedostat + capecitabine)

• Tosedostat (dose determined by Phase I portion of study) by mouth daily Days 1-21 of each 21-day cycle
• Capecitabine by mouth BID Days 1-14 of each 21-day cycle

Group Type: EXPERIMENTAL

Tosedostat

Intervention Type: DRUG

Capecitabine

Intervention Type: DRUG

Fresh tissue biopsy

Intervention Type: PROCEDURE

Patients who have a partial response at the end of cycle 2 will be required to undergo biopsy if deemed safe for the patient and tissue is feasible to obtain.

Interventions

Tosedostat

Intervention Type: DRUG

Capecitabine

Intervention Type: DRUG

Fresh tissue biopsy

Patients who have a partial response at the end of cycle 2 will be required to undergo biopsy if deemed safe for the patient and tissue is feasible to obtain.

Intervention Type: PROCEDURE

Other Intervention Names

Xeloda

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically proven metastatic or inoperable pancreatic adenocarcinoma.
• Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with CT scan or MRI, as >20 mm by chest x-ray, or >10 mm with calipers by clinical exam.
• Must have progressed on, been intolerant to, or refused gemcitabine-based therapy.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Normal bone marrow and organ function as defined below:

• Absolute neutrophil count ≥ 1,000/mcl
• Platelets ≥ 100,000/mcl
• Total bilirubin ≤ 2.0 mg/dL
• Creatinine ≤ 2.0 mg/dL
• AST or ALT ≤2.5 IULN (≤5X IULN if liver metastases are present)
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria

• Chemotherapy < 2 weeks prior to the first planned dose of study treatment.
• Radiotherapy < 3 weeks prior to the first planned dose of study treatment.
• A history of other malignancy ≤ 2 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
• Currently receiving any other investigational agents.
• Known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to tosedostat or capecitabine or other agents used in the study.
• Previous treatment with any aminopeptidase inhibitor.
• Previous exposure to either 5-FU or capecitabine at a systemic dose except for use in concurrent chemoradiation.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency or severe renal impairment (creatinine clearance < 30 mL/min by Cockcroft-Gault formula), as this would preclude use of capecitabine.
• Significant cardiovascular disease defined as:

• Myocardial infarction within 6 months of screening.
• Unstable angina pectoris
• Uncontrolled or clinically significant arrhythmia Grade ≥ 2
• LVEF ≤ below institutional limits at screening
• Congestive heart failure NYHA class III or IV
• Presence of clinically significant valvular heart disease
• Baseline troponin I or T > IULN and b-type natriuretic peptide > IULN.
• Prior exposure to cardiotoxic agent, such as anthracyclines, within 3 months of enrollment.
• Patient must have a QTc interval on ECG ≤ 0.48 seconds by Bazett's calculation at screening.
• Patient may not be taking any drugs that prolong the QT/QTc interval. If patient is on any of these drugs, patient may enroll in the study if the drugs can be discontinued for at least 5 half-lives prior to the first dose of tosedostat and capecitabine.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and/or breastfeeding. Patients that are of childbearing age must have a negative pregnancy test at screening and agree on using contraception during the duration of the study.
• Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with tosedostat or capecitabine. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrea Wang-Gillam, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

201503074

Identifier Type: -

Identifier Source: org_study_id