Phase 2 Study to Assess the Efficacy & Safety of Gemcitabine + Nab Paclitaxel With or Without Dociparstat in Metastatic Pancreatic Cancer Patients

NCT01461915 | Terminated Phase 2

• 1 other identifier: PGX-ODSH-2011-PC1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 16

Brief Summary

This randomized, Phase 2, open label study aims to assess the efficacy and safety of gemcitabine + nab paclitaxel with or without dociparstat (ODSH) as first line treatment of metastatic pancreatic cancer. This study consists of 2 periods: a Run-in Period and a Randomized Period.

Conditions

Metastatic Pancreatic Cancer

Keywords

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients who Achieved Progression-Free Survival

  The primary objective of this study is to evaluate progression-free survival (PFS) according to Response Evaluation Criteria In Solid Tumors (RECIST) Guidelines Version 1.1. This will be assessed from Baseline to disease progression or death (whichever occurred first), for up to 9 months.

  9 months

Secondary Outcomes (1)

• Proportion of Patients who Achieved Overall Survival

  9 months

Study Arms (3)

Run-in

EXPERIMENTAL

During the Run-In Period, patients will receive gemcitabine + nab-paclitaxel + dociparstat to assess the compatibility of the combination. • Nab-paclitaxel + gemcitabine + dociparstat: * Nab-paclitaxel 125 mg/m2 will be administered intravenously (IV) over 30 minutes followed by the administration of gemcitabine IV infusion at 1000 mg/m2 over 30 minutes. Nab paclitaxel + gemcitabine will be administered weekly for 3 weeks followed by 1 week of rest (28-day cycle). * Dociparstat IV bolus at 4 mg/kg will be administered in 5 minutes immediately following the completion of gemcitabine administration. * Dociparstat 48-hour IV continuous infusion at 0.375 mg/kg/hr will be administered immediately following the dociparstat IV bolus administration.

Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Dociparstat

Arm A

EXPERIMENTAL

Patients randomized to Arm A will receive gemcitabine + nab-paclitaxel + dociparstat. • Nab-paclitaxel + gemcitabine + dociparstat: * Nab-paclitaxel 125 mg/m2 will be administered IV over 30 minutes followed by the administration of gemcitabine IV infusion at 1000 mg/m2 over 30 minutes. Nab paclitaxel + gemcitabine will be administered weekly for 3 weeks followed by 1 week of rest (28-day cycle). * Dociparstat IV bolus at 4 mg/kg will be administered in 5 minutes immediately following the completion of gemcitabine administration. * Dociparstat 48-hour IV continuous infusion at 0.375 mg/kg/hr will be administered immediately following the dociparstat IV bolus administration.

Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Dociparstat

Arm B

ACTIVE COMPARATOR

Patients randomized to Arm B will receive gemcitabine + nab-paclitaxel. • Nab-paclitaxel + gemcitabine: o Nab-paclitaxel 125 mg/m2 will be administered IV over 30 minutes followed by the administration of gemcitabine IV infusion at 1000 mg/m2 over 30 minutes. Nab paclitaxel + gemcitabine will be administered weekly for 3 weeks followed by 1 week of rest (28-day cycle).

Drug: Nab paclitaxel; Drug: Gemcitabine

Interventions

Nab paclitaxel DRUG

Nab-paclitaxel 125 mg/m2 will be administered IV over 30 minutes. Nab-paclitaxel will be administered weekly for 3 weeks followed by 1 week of rest (28-day cycle).

Also known as: Abraxane

Arm A; Arm B; Run-in

Gemcitabine DRUG

Following the completion of nab-paclitaxel administration, gemcitabine IV infusion at 1000 mg/m2 will be administered over 30 minutes. Gemcitabine will be administered weekly for 3 weeks followed by 1 week of rest (28-cycle).

Arm A; Arm B; Run-in

Dociparstat DRUG

Following the completion of gemcitabine administration, dociparstat IV bolus at 4 mg/kg will be administered in 5 minutes immediately after completion of gemcitabine administration. Immediately following the dociparstat IV bolus administration, dociparstat 48-hour IV continuous infusion at 0.375 mg/kg/hr will be administered.

Also known as: ODSH, 2-O, 3-O Desulfated Heparin, Dociparstat sodium

Arm A; Run-in

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all the following criteria to be eligible for this study:
• Has histologically confirmed adenocarcinoma of the pancreas that is metastatic and for which potential curative measures, such as resection of an isolated metastasis, are not available. Patients with islet cell neoplasms will be excluded.
• Has ≥ 1 metastatic tumors measurable by computerized tomography (CT) scan AND a serum carbohydrate antigen (CA) 19-9 measurement \>2 times the upper limit of normal. Patients must have measurable disease, defined as at least 1 lesion that could be accurately measured in at least 1 dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
• Is male or non-pregnant and non-lactating female and ≥ 18 to ≤ 75 years of age. If a female patient is of child-bearing potential, she must have a negative serum pregnancy test documented within 72 hours prior to the first administration of study drug and on Day 1 of each cycle thereafter. If sexually active, the patient must agree to use contraception prior to study entry and for the duration of study participation.
• Must have received no prior radiotherapy or chemotherapy for metastatic disease. Patients who have received radiotherapy or chemotherapy as adjuvant or neo-adjuvant therapy for locally advanced disease 6 months or more prior to enrollment into this study are eligible.
• Has adequate biological parameters as demonstrated by the following blood counts at Screening (obtained ≤14 days prior to randomization) and at Baseline-Day 0: Absolute neutrophil count (ANC) ≥1.5 × 109/L; Platelet count ≥ 100,000/mm3 (100 × 109/L); Hemoglobin (Hgb) ≥ 9 g/dL.
• Has the following blood chemistry levels at Screening (obtained ≤14 days prior to randomization) and at Baseline-Day 0:
• Aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT) ≤ 2.5 × upper limit of normal range (ULN), unless liver metastases are present, then ≤5 × ULN is allowed. Total bilirubin ≤1.5 × ULN.
• Serum creatinine (Cr) within normal limits or calculated clearance ≥60 mL/min/1.73 m2 for patients with creatinine (Cr) levels above or below the institutional normal value. If using Cr clearance, actual body weight should be used for calculating Cr clearance (e.g., using the Cockcroft-Gault formula).
• Has acceptable coagulation studies at Screening (obtained ≤14 days prior to randomization) as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (±15%).
• Has an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤1.
• Has been informed about the nature of the study, and agrees to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities.

You may not qualify if:

• If a patient meets any of the following criteria, they are not eligible to participate in this study:
• Has brain metastases.
• Has only locally advanced disease.
• Has experienced an increase of ECOG score to \>1 between Screening and Randomization.
• Requires continuous treatment with coumadin or other oral or parenteral anticoagulation (heparin, low molecular weight heparin \[LMWH\], heparinoids) to prevent or treat thromboembolic disease. The use of prophylactic antiplatelet drugs such as clopidogrel and aspirin are allowed before and during the study.
• Has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Has undergone major surgery, other than diagnostic surgery (i.e., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Randomization in this study.
• Has a history of allergy or hypersensitivity to any of the study drugs, their pharmaceutical class, or any of their excipients.
• Has a concomitant serious medical or psychiatric illness that, in the opinion of the Investigator, could compromise the patient's safety or the study data integrity.
• Is enrolled in any other clinical protocol or investigational trial that involves administration of anti-neoplastic compounds for the treatment of metastatic pancreatic cancer.
• Is unwilling or unable to comply with study procedures.
• Nab-paclitaxel is metabolized by cytochrome P450 (CYP) 2C8 and CYP3A4. Co-administration of substrates, inhibitors of CYP2C8 and/or CYP3A4 with nab-paclitaxel is not allowed. The following medications and substances are not allowed during the study: ritonavir, saquinavir, indinavir, nelfinavir, rifampicin, carbamazepine, phenytoin, efavirenz, or nevirapine, grapefruit (juice or seeds) or some herbals like St. John's wort.
• Has risk factors for or a history of Torsades des Pointes (TdP), or a significant QT prolongation that, in the opinion of the Investigator, may place the patient at risk.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead
• Translational Drug Development: collaborator

Study Sites (16)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Disney Family Cancer Center

Burbank, California, 91505, United States

Location

Marin Cancer Care

Greenbrae, California, 94904, United States

Location

Scripps Clinic Torrey Pines ( Green Hospital)

La Jolla, California, 92037, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Loyola University Medical Center/Cardinal Bernardin Cancer Center

Maywood, Illinois, 60153, United States

Location

Indiana University Health, Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

Fesit-Weiller Cancer Center

Shreveport, Louisiana, 71130, United States

Location

Saint Mary's Health Care

Grand Rapids, Michigan, 49503, United States

Location

Summa Health System - Cooper Cancer Center

Akron, Ohio, 44304, United States

Location

Thomas Jefferson University [Kimmel Cancer Center]

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UPMC Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical University of South Carolina Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

South Texas Oncology & Hematology

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011 Dec 1;29(34):4548-54. doi: 10.1200/JCO.2011.36.5742. Epub 2011 Oct 3.

  PMID: 21969517 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Taxes; Albumin-Bound Paclitaxel; Gemcitabine; N-desulfated,2-O,3-O-desulfated heparin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Mitesh J Borad, MD

  Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic , Scottsdale Arizona

  PRINCIPAL INVESTIGATOR

• Stephen Marcus, MD

  ParinGenix Inc, Weston FL

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2011
• First Posted: October 28, 2011
• Study Start: November 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: June 1, 2015
• Last Updated: June 6, 2022

Record last verified: 2022-06

Locations

US (16)