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Pancreatic NeoplasmsPhase 1NCT02267707

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

A Phase 1 study testing nab-paclitaxel and Gemcitabine in people with Pancreatic Neoplasms and Cholestasis, run by Celgene at 6 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreatic Neoplasms, Cholestasis
What is being tested?
nab-paclitaxel and Gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
6 sitesin 2 countries
Study dates
27 May 2015to 10 Feb 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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).
  • Subject has a Karnofsky performance status (KPS) ≥ 70%.
  • Significant or symptomatic amounts of ascites should be drained prior to Cycle 1 Day 1. Pain symptoms should be stable and should not require modifications in analgesic management prior to Cycle 1 Day 1.
  • Females of childbearing potential (FCBP) (defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must:
  • Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting IP therapy (including dose interruptions), and while on study medication or for a longer period if required by local regulations following the last dose of IP; and
  • Have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy. This applies even if the subject practices true abstinence* from heterosexual contact.
  • Male subjects must practice true abstinence* or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following IP discontinuation, even if he has undergone a successful vasectomy.
  • True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Note: Periodic abstinence (e.g, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
  • Able to adhere to the study visit schedule and other protocol requirements.

Who cannot join

  • 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.
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  • 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.
  • Any condition that confounds the ability to interpret data from the study.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

Germany4 sites

  • Charite -Universitätsmedizin Berlin

    Berlin, 13353

  • St. Josef-Hospital

    Bochum, 44791

  • University Hospital of Ulm

    Ulm, 89081

  • Universitatsklinikum Wurzburg

    Würzburg, 97080

Other trials in Germany

United States2 sites

  • Barbara Ann Karmanos Cancer Center

    Detroit, Michigan, 48201

  • Mayo Clinic Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: A Phase 1, Multicenter, Open-label, Dose-escalation Study to Investigate the Safety and Pharmacokinetics of Nab®-Paclitaxel (ABI-007) Plus Gemcitabine in Subjects With Advanced Pancreatic Cancer Who Have Cholestatic Hyperbilirubinemia Secondary to Bile Duct Obstruction

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.

Read the detailed description

There are 2 treatment cohorts in this study based on the predose total bilirubin levels on Cycle 1 Day 1 (Cohort 1 > 1.5 x Upper Limit of Normal [ULN] to 3 x ULN bilirubin and Cohort 2 > 3 x ULN to 5 x ULN). Enrollment of subjects into Cohort 2 will only proceed after a review of the safety and pharmacokinetic (PK) data for all subjects in Cohort 1 has been completed by the Safety Monitoring Committee. The study is following a 3+3 dose escalation scheme within each dose level cohort group. A total of 3 subjects will initially be enrolled to the starting dose level in each cohort. The dose of the study regimen in each cohort will be escalated (or reduced) according to tolerability.

Keywords
nab®-paclitaxel, ABI-007, Abraxane, Advanced Pancreatic Cancer, Cholestatic Hyperbilirubinemia, Bile Duct Obstruction, Pancreatic Cancer
Medical subject headings
Pancreatic Neoplasms, Cholestasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nab-paclitaxelDrug

    Also called Abraxane, ABI-007

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

  • GemcitabineDrug

    Also called Gemzar

    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.

Study groups in NCT02267707
Study groupRoleWhat they receive
Cohort 1 - Bilirubin level > 1.5 x ULN to 3 x ULNExperimental4 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
Receives: Drug: nab-paclitaxel; Drug: Gemcitabine
Cohort 2 - Bilirubin level > 3 x ULN to 5 x ULNExperimental6 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
Receives: Drug: nab-paclitaxel; Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 20 months

  2. Pharmacokinetics - Cmax

    Maximum observed concentration in plasma

    Measured: Days 1 and 3

  3. Pharmacokinetics - AUC

    Area under the plasma concentration-time curve

    Measured: Days 1 and 3

  4. Pharmacokinetics - T1/2

    Terminal half-life (T1/2)

    Measured: Days 1 and 3

  5. Pharmacokinetics - Vss

    Apparent volume of distribution at the steady state

    Measured: Days 1 and 3

  6. Pharmacokinetics - CL

    Apparent total body clearance

    Measured: Days 1 and 3

Secondary outcomes (5)

  1. Tumor response

    Objective tumor response based on computed tomography (CT)/ Magnetic Resonance Imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST Version) 1.1 guidelines per Investigator assessment

    Measured: Up to 28 months

  2. Progression-free survival

    Progression-free survival according to RECIST Version 1.1 guidelines per investigator assessment

    Measured: Up to 28 months

  3. Overall survival

    Number of participants who are alive or dead

    Measured: Up to 28 months

  4. Adverse Events

    Incidence of treatment-emergent adverse events (TEAE) and serious adverse events. TEAE are defined as any event that begins or worsens in grade after the start of Investigational Product through 28 days after the last does of Investigational Product.

    Measured: Up to 28 months

  5. Gemcitabine PK profile

    Evaluate the pharmacokinetic profile of gemcitabine

    Measured: Up to 28 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2014 (estimated)
  2. Study start27 May 2015
  3. Primary completion10 Feb 2016
  4. Study completion10 Feb 2016

Why it stopped: Study population more infrequent than estimated. No study-related safety issues and no safety concerns were identified for the study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02267707
Sponsor's protocol ID
ABI-007-PANC-004
Status last verified
Oct 2019
First submitted
1 Oct 2014
Last updated
1 Nov 2019
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing nab-paclitaxel and Gemcitabine in people with Pancreatic Neoplasms and Cholestasis, run by Celgene at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Germany, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study population more infrequent than estimated. No study-related safety issues and no safety concerns were identified for the study.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (time frame: Up to 20 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02267707.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019.

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