- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02352831
Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma
Phase I/II Study Combining Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase I (tosedostat + capecitabine)
|
Other Names:
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)
|
Other Names:
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I Only: Recommended Phase II Dose of Tosedostat
Time Frame: Completion of cycle 1 of all participants in Phase I portion of study (approximately 14 months)
|
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. |
Completion of cycle 1 of all participants in Phase I portion of study (approximately 14 months)
|
Phase I Only: Number of Participants Who Experience Dose-limiting Toxicities (DLTs)
Time Frame: Completion of cycle 1 of all participants in Phase I portion of study (approximately 14 months)
|
|
Completion of cycle 1 of all participants in Phase I portion of study (approximately 14 months)
|
Progression-free Survival (PFS) Rate
Time Frame: 3 months
|
|
3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR)
Time Frame: Up to 18 months
|
|
Up to 18 months
|
Time-to-progression (TTP)
Time Frame: Up to 24 months
|
-Progressive disease (PD)
|
Up to 24 months
|
Overall Survival Rate (OS)
Time Frame: Up to 1 year from completion of treatment (median treatment length 81.50 days (28.00-346.00)
|
Up to 1 year from completion of treatment (median treatment length 81.50 days (28.00-346.00)
|
|
Number of Participants With a CA19-9 Response
Time Frame: Completion of treatment (median treatment length 81.50 days (28.00-346.00)
|
|
Completion of treatment (median treatment length 81.50 days (28.00-346.00)
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Adenocarcinoma
- Pancreatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Capecitabine
- Tosedostat
Other Study ID Numbers
- 201503074
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pancreatic Cancer
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CelgeneWithdrawnPancreatic Ductal Adenocarcinoma | Stage III Pancreatic Cancer | Stage IV Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic CancerUnited States
-
University of NebraskaNational Cancer Institute (NCI)CompletedPancreatic Adenocarcinoma | Stage III Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage II Pancreatic Cancer | Stage I Pancreatic Cancer | Resectable Pancreatic Carcinoma | Stage IA Pancreatic Cancer | Stage IB Pancreatic CancerUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedPancreatic Adenocarcinoma | Resectable Pancreatic Cancer | Stage III Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic Cancer | Poorly Differentiated Malignant Neoplasm | Undifferentiated Pancreatic CarcinomaUnited States
-
Virginia Commonwealth UniversityNational Cancer Institute (NCI)CompletedPancreatic Adenocarcinoma | Recurrent Pancreatic Carcinoma | Stage III Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic CancerUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)WithdrawnStage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic Cancer
-
National Cancer Institute (NCI)CompletedStage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic CancerUnited States
-
University of Wisconsin, MadisonCompletedStage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic CancerUnited States
-
Fudan UniversityUnknownStage ⅠA Pancreatic Cancer | Stage ⅠB Pancreatic Cancer | Stage ⅡA Pancreatic Cancer | Stage ⅡB Pancreatic CancerChina
-
University of UtahNovartis PharmaceuticalsRecruitingMetastatic Pancreatic Carcinoma | Unresectable Pancreatic Carcinoma | Stage III Pancreatic Cancer | Stage IV Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage II Pancreatic CancerUnited States
-
Shanghai Zhongshan HospitalFudan UniversityNot yet recruitingPancreatic Cancer Stage III | Pancreatic Cancer, Stage IB | Pancreatic Cancer, Stage IIA | Pancreatic Cancer, Stage IIBChina
Clinical Trials on Capecitabine
-
Sun Yat-sen UniversityChengdu Biostar PharmaceuticalsNot yet recruitingBreast Neoplasms | Locally Advanced or Metastatic Breast CancerChina
-
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityRecruiting
-
Hoffmann-La RocheCompletedBreast Cancer, Colorectal CancerNew Zealand, Australia, United Kingdom
-
Binghe XuHoffmann-La RocheUnknownSkin Diseases | Neoplasms by Site | Breast Neoplasms | Breast Diseases | Neoplasm MetastasisChina
-
Jules Bordet InstituteCompletedBreast Cancer | Elderly PatientsBelgium
-
Samsung Medical CenterCompletedAdvanced or Recurrent Esophageal Squamous Cell CarcinomaKorea, Republic of
-
Fudan UniversityCompletedMetastatic Breast CancerChina
-
Cancer Institute and Hospital, Chinese Academy...Hoffmann-La RocheUnknownCarcinoma, Invasive Ductal, BreastChina
-
The First Affiliated Hospital of Zhengzhou UniversityRecruiting
-
Jiangxi Provincial Cancer HospitalNot yet recruitingNasopharyngeal Carcinoma | Maintenance Therapy | High-Risk Cancer