Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Tosedostat

Antimetabolites

Enzyme Inhibitors

* 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.

* 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

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.

Fresh tissue biopsy

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

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.

Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma

Phase I/II Study Combining Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma

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.

* Possibly/probably/definitely related to study treatment in 1st cycle (cyc)

  \*Grade (Gr) 4 neutropenia \>7 day, Febrile neutropenia of any duration with temperature ≥ 38.5 °C, Gr 4 anemia requires transfusion therapy on more than 2 occasions in 7 days, Gr 4 thrombocytopenia
* Possibly/probably/definitely related gr. 3/4 non-hematologic toxicity that occurs 1st cyc with the following EXCEPTIONS:

  * Gr 3 nausea/vomiting/diarrhea/anorexia \<72 hours that returns to Gr 1 prior to the start of cyc 2, Gr 3 hand-foot syndrome will only be considered a DLT for patients who have received 1 week of supportive care treatment with no improvement, Gr 3 fatigue that returns to Gr 1 prior to the start of cyc 2, Gr 3 flu-like symptoms \<72 hours that returns to Gr 1 prior to start of cyc 2, Gr 3 arthralgia or myalgias \<72 hours that return to Gr 1 prior to the start of cyc 2, Gr 3 potassium/phosphorus/magnesium that is asymptomatic or of non-clinical significance \<72 hours, Gr 3 hypoalbuminemia

* 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.

* 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).

-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

* CA19-9 is a tumor marker that is used in the management of pancreatic cancer. Rising CA19-9 levels may mean the tumor is growing and decreasing CA19-9 levels may mean the tumor is shrinking or the amount of cancer in the body is decreasing
* A CA19-9 response means that the tumor marker has decreased over baseline (before treatment started) levels

Washington University School of Medicine

Phase I (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
* 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.

Phase II (Tosedostat + Capecitabine)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Baseline CA19-9

This outcome measure is for Phase I participants only.

Phase I Only: Recommended Phase II Dose of Tosedostat

Phase I Only: Number of Participants Who Experience Dose-limiting Toxicities (DLTs)

* Tosedostat by mouth daily Days 1-21 of each 21-day cycle
* Capecitabine 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.

Phase I and Phase II Combined

Progression-free Survival (PFS) Rate

Overall Response Rate (ORR)

Time-to-progression (TTP)

* Tosedostat by mouth daily Days 1-21 of each 21-day cycle
* Capecitabine by mouth BID Days 1-14 of each 21-day cycle

Spots Global Cancer Trial Database for fresh tissue biopsy