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Trial record 1 of 1 for:    NCT02352831
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Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma

This study is currently recruiting participants.
See Contacts and Locations
Verified January 2017 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT02352831
First received: January 28, 2015
Last updated: January 26, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention Phase
Pancreatic Cancer Cancer of Pancreas Cancer of the Pancreas Pancreas Cancer Drug: Tosedostat Drug: Capecitabine Procedure: Fresh tissue biopsy Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase I/II Study Combining Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Phase I only: Recommended Phase II dose and dose-limiting toxicities (DLTs) [ Time Frame: Estimated to be 7 months (completion of cycle 1 of all participants in Phase I portion of study) ]

    The recommended phase 2 dose (RP2D) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. If 0 or 1 of 6 patients in Dose Level 1 experience DLT during the first cycle, Dose Level 1 will be presumed to be the RP2D.

    DLTs are followed through completion of the first cycle.


  • Phase II only: Progression-free survival (PFS) rate [ Time Frame: 3 months ]
    • PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
    • Progressive disease (PD)

      • Target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
      • Non target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.


Secondary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: Up to 18 months ]
    • ORR = Complete response + partial response
    • Target lesions

      • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
      • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
    • Non target lesions *Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).

  • Time-to-progression (TTP) [ Time Frame: Up to 18 months ]

    -Progressive disease (PD)

    • Target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
    • Non target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase

  • Overall survival (OS) [ Time Frame: Up to 18 months ]
  • CA19-9 response [ Time Frame: Completion of treatment (estimated to be 3 months) ]
    CA19-9 is a tumor marker that is used in the management of pancreatic cancer.


Estimated Enrollment: 42
Actual Study Start Date: August 31, 2015
Estimated Study Completion Date: March 31, 2019
Estimated Primary Completion Date: December 31, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I (tosedostat + capecitabine)
  • Tosedostat by mouth daily Days 1-21 of each 21-day cycle
  • Capecitabine by mouth BID Days 1-14 of each 21-day cycle
Drug: Tosedostat Drug: Capecitabine
Other Name: Xeloda
Procedure: 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.
Experimental: 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
Drug: Tosedostat Drug: Capecitabine
Other Name: Xeloda
Procedure: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02352831

Contacts
Contact: Andrea Wang-Gillam, M.D., Ph.D. (314) 362-5740 awang-gillam@wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Andrea Wang-Gillam, M.D., Ph.D.    314-362-5740    awang-gillam@wustl.edu   
Sub-Investigator: A. Craig Lockhart, M.D.         
Sub-Investigator: Joel Picus, M.D.         
Sub-Investigator: Anna Roshal, M.D.         
Sub-Investigator: Benjamin Tan, M.D.         
Sub-Investigator: Kian-Huat Lim, M.D., Ph.D.         
Sub-Investigator: Rama Suresh, M.D.         
Sub-Investigator: Andrea Teague, M.D.         
Sub-Investigator: Manik Amin, M.D.         
Sub-Investigator: Shannon Grass, A.N.P         
Sub-Investigator: Jan Hanneken, A.N.P         
Sub-Investigator: Susan Hays, A.N.P         
Sub-Investigator: Ashley Morton, A.N.P         
Sub-Investigator: Michael Naughton, M.D.         
Sub-Investigator: Peter Oppelt, M.D.         
Sub-Investigator: Haeseong Park, M.D.         
Sub-Investigator: Alex Politsmakher, M.D.         
Sub-Investigator: Caron Rigden, M.D.         
Sub-Investigator: Jane Sherman, A.N.P         
Sub-Investigator: Amber Smith, A.N.P         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Andrea Wang-Gillam, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02352831     History of Changes
Other Study ID Numbers: 201503074
Study First Received: January 28, 2015
Last Updated: January 26, 2017
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

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Capecitabine
Glycine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Glycine Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 27, 2017