Safety and Efficacy Study of PRI-724 Plus Gemcitabine in Subjects With Advanced or Metastatic Pancreatic Adenocarcinoma

NCT01764477 | Completed Phase 1

• 1 other identifier: PRI-724-102
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

Laboratory studies suggest that the study drug may stop cancer cells from growing by affecting an interaction between proteins in the cells referred to as cAMP-response element-binding protein and ß-catenin. The purpose of this research study is to determine the highest safe dose of study drug that may be used when it is given together with a chemotherapy drug to patients with cancer of the pancreas.

Conditions

Advanced Pancreatic Cancer; Metastatic Pancreatic Cancer; Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• The Maximum Tolerated Dose (MTD) of PRI-724 + Gemcitabine measured by the number of dose limiting toxicities (DLTs) that occur.

  If no DLT occurs in the first 3 patients of a cohort, the dose will be escalated to the next dose cohort. If 1 DLT occurs in the first 3 patients of a cohort, that cohort is expanded to 6 patients. If more than 1 DLT occurs in a 6 patient cohort, escalation is stopped \& next lower dose is expanded to 12 patients to confirm the MTD.

  18 months. DLTs will be measured as they occur throughout the patients' time on study.

Secondary Outcomes (5)

• Pharmacokinetic parameters of C max , T max , AUC (tau), and t ½.

  C 1 D 1 hrs 0, 1, 2, D 8 hrs 0, :15, :30, 1, 2, 4, 6, D 9 hrs 24, D 15 at hrs 0

• Pharmacodynamic mRNA expression of survivin

  C 1 D 1, D 8, D 15, D 22, All Cycles D 22, end of treatment

• Evaluation of antineoplastic activity of PRI-724 + gemcitabine per RECIST 1.1 criteria

  Screening, end of C 2, every 2 cycles, end of treatment

• MMP7 levels in blood as ng/ml

  C 1 Wk 1, Wk 4, Wk 4 all cycles, end of treatment

• Gene expressions in hair follicle epithelial cells

  Screening, C 1 D 14, C 2 Wk 4, end of treatment

Study Arms (1)

PRI-724 and Gemcitabine

EXPERIMENTAL

This study will have one arm: all enrolled subjects will be treated with both PRI-724 and Gemcitabine.

Drug: PRI-724

Interventions

PRI-724 DRUG

Gemcitabine: 1000 mg/m2 IV over 30 minutes; once weekly dosing; 3 weeks on with 1 week recovery (4 weeks per cycle) PRI-724: Cohort 1: 320 mg/m2/day; Cohort 2: 640 mg/m2/day; Cohort 3: 905 mg/m2/day; Continuous IV over 24 hours; daily x 7 days; 1 week on with 1 week recovery × 2 (4 weeks per cycle)

PRI-724 and Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, \> 18 years of age.
• Patients with a documented (histologically- or cytologically-proven) epithelial cell/adenocarcinoma of the pancreas that is relapsed, locally advanced, or metastatic.
• Patients with measurable or evaluable disease according to the response evaluation criteria in solid tumors
• Patients eligible for second-line therapy after failing first-line therapy with the regimen FOLFIRINOX.
• Patients with a malignancy that is currently not amenable to surgical intervention, due to either medical contraindications or non-resectability of the tumor.
• Patients with a Karnofsky Performance Status of 70% to 100% (or equivalent, Eastern Cooperative Oncology Group \[ECOG\] performance status of 0 or 1); Performance Status Evaluation), and an anticipated life expectancy of ≥ 3 months.
• Patients, both male and female, who are either not of childbearing potential or who agree to use a medically effective method of contraception during the study and for 3 months after the last dose of study drug.
• Patients with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol.

You may not qualify if:

• Women who are pregnant or lactating. Women of child-bearing potential (WOCBP) and fertile men with a WOCBP partner, not using adequate birth control.
• Patients with islet cell tumors or other non-epithelial cell malignancies of the pancreas.
• Patients with known CNS (or leptomeningeal) metastases not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
• Patients with an active second malignancy within the last 2 years with the exception of:
• Treated, non-melanoma skin cancers
• Treated CIS of the breast or cervix
• Controlled, superficial bladder carcinoma
• T1a or b prostate carcinoma involving \< 5% of resected tissue and PSA within normal limits (WNL) since resection
• Patients with any of the following hematologic abnormalities at baseline:
• Hemoglobin \< 9.0 g/dL
• Absolute neutrophil count (ANC) \< 1,500 per mm3
• Platelet count \< 100,000 per mm3
• Patients with any of the following serum chemistry abnormalities at baseline:
• Total bilirubin \> 1.5× the ULN for the institution, unless considered due to Gilbert's Syndrome
• AST or ALT \> 3× the ULN for the institution (\> 5× ULN if due to hepatic involvement by tumor)

Sponsors & Collaborators

• Prism Pharma Co., Ltd.: lead
• inVentiv Health Clinical: collaborator

Study Sites (5)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Washington Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

ICG 001

Condition Hierarchy (Ancestors)

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

Study Officials

• Robert R. McWilliams, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2012
• First Posted: January 9, 2013
• Study Start: April 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: August 17, 2017

Record last verified: 2015-10

Locations

US (5)