Pharmacokinetic and Safety Study of Nab®-Paclitaxel (ABI-007) Plus Gemcitabine in Subjects With Advanced Pancreatic Cancer Who Have Cholestatic Hyperbilirubinemia

NCT02267707 | Terminated Phase 1 DMC

• 1 other identifier: ABI-007-PANC-004
• Study Type: interventional
• Target: 1
• Locations: 2 countries
• Sites: 6

Brief Summary

The purpose of this study is to determine the safety and pharmacokinetic profile of nab®-paclitaxel (ABI-007) plus gemcitabine in subjects with advanced pancreatic cancer who have cholestatic hyperbilirubinemia secondary to bile duct obstruction.

Conditions

Pancreatic Neoplasms; Cholestasis

Keywords

nab®-paclitaxel; ABI-007; Abraxane; Advanced Pancreatic Cancer; Cholestatic Hyperbilirubinemia; Bile Duct Obstruction; Pancreatic Cancer

Outcome Measures

Primary Outcomes (6)

• Maximum Tolerated Dose

  Determination of Maximum Tolerated Dose which is defined as the highest dose which induced a dose limiting toxicity in 0 or 1 out of 6 subjects during their first cycle of treatment.

  Up to 20 months

• Pharmacokinetics - Cmax

  Maximum observed concentration in plasma

  Days 1 and 3

• Pharmacokinetics - AUC

  Area under the plasma concentration-time curve

  Days 1 and 3

• Pharmacokinetics - T1/2

  Terminal half-life (T1/2)

  Days 1 and 3

• Pharmacokinetics - Vss

  Apparent volume of distribution at the steady state

  Days 1 and 3

• Pharmacokinetics - CL

  Apparent total body clearance

  Days 1 and 3

Secondary Outcomes (5)

• Tumor response

  Up to 28 months

• Progression-free survival

  Up to 28 months

• Overall survival

  Up to 28 months

• Adverse Events

  Up to 28 months

• Gemcitabine PK profile

  Up to 28 months

Study Arms (2)

Cohort 1 - Bilirubin level > 1.5 x ULN to 3 x ULN

EXPERIMENTAL

4 dose levels may be given in this arm as follows: nab-paclitaxel 75 mg/m2; gemcitabine 600 mg/m2 nab-paclitaxel 100 mg/m2; gemcitabine 800 mg/m2 nab-paclitaxel 125 mg/m2; gemcitabine 800 mg/m2 nab-paclitaxel 125 mg/m2; gemcitabine 1000 mg/m2

Drug: nab-paclitaxel; Drug: Gemcitabine

Cohort 2 - Bilirubin level > 3 x ULN to 5 x ULN

EXPERIMENTAL

6 dose levels may be given in this arm as follows: nab-paclitaxel 75 mg/m2 nab-paclitaxel 75 mg/m2; gemcitabine 600 mg/m2 nab-paclitaxel 100 mg/m2; gemcitabine 600 mg/m2 nab-paclitaxel 125 mg/m2; gemcitabine 600 mg/m2 nab-paclitaxel 125 mg/m2; gemcitabine 800 mg/m2 nab-paclitaxel 125 mg/m2; gemcitabine 1000 mg/m2

Drug: nab-paclitaxel; Drug: Gemcitabine

Interventions

nab-paclitaxel DRUG

Subjects will receive nab-paclitaxel as an intravenous infusion over approximately 30 minutes on Days 1, 8 and 15 of a 28-day cycle.

Also known as: Abraxane, ABI-007

Cohort 1 - Bilirubin level > 1.5 x ULN to 3 x ULN; Cohort 2 - Bilirubin level > 3 x ULN to 5 x ULN

Gemcitabine DRUG

Gemcitabine will be administered immediately after nab-paclitaxel as an intravenous infusion over approximately 30 minutes on Days 1, 8 and 15 of a 28-day cycle.

Also known as: Gemzar

Cohort 1 - Bilirubin level > 1.5 x ULN to 3 x ULN; Cohort 2 - Bilirubin level > 3 x ULN to 5 x ULN

Eligibility Criteria

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

You may qualify if:

• Subject has definitive histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic adenocarcinoma (islet cell neoplasms are excluded) that is measurable by RECIST Version 1.1 guidelines.
• Initial diagnosis of advanced stage disease must have occurred ≤ 6 weeks prior to starting Cycle 1 Day 1. NOTE: The clock for this time interval starts with the date of last evaluation confirming advanced disease (either biopsy or imaging results).
• Subject has confirmed cholestatic hyperbilirubenemia due to bile duct obstruction. Subjects who have liver dysfunction due to metastasis alone are excluded.
• Subject must have received no prior therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. If a subject received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least 6 months after completing the last dose of gemcitabine.
• For those patients who had a biliary stent inserted, 2 stable bilirubin readings within 48 to 72 hours of each other taken at least 5 days and not more than 14 days post-stenting must be obtained. In addition, there should be no complications (eg, infection) present and bilirubin levels should have stabilized (2 readings with total bilirubin within 20% of each other) before administering first treatment.
• Males and females ≥ 18 years of age at the time of signing the informed consent document (ICD).
• Subject has adequate biological parameters as demonstrated by the following blood counts at screening (obtained ≤ 14 days prior to starting Cycle 1 Day 1):
• Absolute neutrophil count (ANC) ≥ 1500 (1.5 × 109/L) cells/mm3;
• Platelet count ≥ 100,000 (100 × 109/L) cells/mm3;
• Hemoglobin (Hgb) ≥ 9 g/dL.
• Subject has the following blood chemistry levels at screening (obtained ≤ 14 days prior to starting Cycle 1 Day 1):
• AST (SGOT), ALT (SGPT) ≤ 5 × ULN is allowed:
• Serum creatinine within normal limits or calculated clearance ≥ 50 mL/min/1.73 m2 for subjects with serum creatinine levels above or below the institutional normal value. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (eg, using the Cockroft-Gault formula). For subjects with a body mass index (BMI) \> 30 kg/m2, lean body weight should be used instead.
• Subject has acceptable coagulation studies (obtained ≤ 14 days prior to starting Cycle 1 Day 1) partial thromboplastin time (PTT) \< 1.2 x ULN and INR ≤ 1.5 x ULN.
• Subject has no clinically significant abnormalities in urinalysis results (obtained ≤ 14 days prior to starting Cycle 1 Day 1).

You may not qualify if:

• Subject has known brain metastases.
• Any other active malignancy. Any other previous malignancy is allowed providing that the tumor was curatively resected and there is no evidence of recurrence within 12 months prior to enrolment to the study. In addition, adequately treated in-situ carcinoma of the cervix, uteri, or non-melanonatous skin cancer are allowed provided that all treatment was completed 6 months prior to enrollment.
• Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Subject has known historical or active infection with HIV (human immunodeficiency virus), hepatitis B, or hepatitis C or subject receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the Investigator, increase the risk of serious neutropenic complications.
• Subject has undergone major surgery for any reason, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Cycle 1 Day 1 of treatment in this study.
• Subject has a history of a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or electrocardiogram (ECG) abnormality, cerebrovascular accident, transient ischemic attack, seizure disorder or clinically significant cardiac dysrhythmia or electrocardiogram (ECG) abnormality, within 6 months prior to Cycle 1 Day 1.
• Subject has a history of allergy or hypersensitivity to nab-paclitaxel or gemcitabine or any of their excipients.
• Subject uses medication known to be strong inducers of CYP3A4 and CYP2C8 (Section 9.2).
• History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).
• Subjects with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
• History of chronic leukemias (eg, chronic lymphocytic leukemia).
• Subject is enrolled in any other clinical protocol or investigational trial with an interventional agent or assessments that may interfere with study procedures.
• Subject is unwilling or unable to comply with study procedures.
• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

Sponsors & Collaborators

• Celgene: lead

Study Sites (6)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Barbara Ann Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Charite -Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

St. Josef-Hospital

Bochum, 44791, Germany

Location

University Hospital of Ulm

Ulm, 89081, Germany

Location

Universitatsklinikum Wurzburg

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Cholestasis

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Bile Duct Diseases; Biliary Tract Diseases

Intervention Hierarchy (Ancestors)

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

• Alfredo Romano, MD

  Celgene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2014
• First Posted: October 17, 2014
• Study Start: May 27, 2015
• Primary Completion: February 10, 2016
• Study Completion: February 10, 2016
• Last Updated: November 1, 2019

Record last verified: 2019-10

Locations

DE (4); US (2)