Clinical Trials /

Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab in Pancreatic Cancer Patients

NCT02767557

Description:

This is a multicenter center, 2-arms prospective randomized phase II trial which evaluates whether tocilizumab with gemcitabine/nab-paclitaxel is more effective than gemcitabine/nab-paclitaxel.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab in Pancreatic Cancer Patients
  • Official Title: A Multinational, Randomized, Phase II Study of the Combination of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab, an IL-6R Inhibitor, as First-line Treatment in Patients With Locally Advanced or Metastatic Pancreatic Cancer.

Clinical Trial IDs

  • ORG STUDY ID: GI1612
  • NCT ID: NCT02767557

Conditions

  • Unresectable Pancreatic Carcinoma

Interventions

DrugSynonymsArms
Tocilizumab(ACTEMRA®)Tocilizumab & Gemcitabine and nab-Paclitaxel
GemcitabineGemcitabine and nab-Paclitaxel
nab-PaclitaxelABRAXANE®Gemcitabine and nab-Paclitaxel

Purpose

This is a multicenter center, 2-arms prospective randomized phase II trial which evaluates whether tocilizumab with gemcitabine/nab-paclitaxel is more effective than gemcitabine/nab-paclitaxel.

Detailed Description

      The development of new effective treatment strategies remains a major challenge in patients
      with PC. High levels of IL-6 and presence of a systemic inflammatory response in PC patients
      have been reported to correlate with worse survival. Preclinical PC models have clearly shown
      that anti-IL-6-receptor antibody tocilizumab in combination with chemotherapy reduced tumor
      growth, number of distant metastases and the local recurrence rate. Thus, blockade of
      IL-6-regulated signaling pathways represents a promising approach in combination with
      chemotherapy. Elevated C-reactive protein (CRP) alone or in combination with hypoalbuminaemia
      (Modified Glasgow Prognostic Score - mGPS) are induced by IL-6 and could feasibly represent
      surrogate markers for IL-6 bioactivity to stratify patients likely to gain benefit through
      targeting IL-6.
    

Trial Arms

NameTypeDescriptionInterventions
Tocilizumab & Gemcitabine and nab-PaclitaxelExperimentalTocilizumab: 8 mg/kg given I. V. on day 1 over 60 minutes every 28 day cycle. Gemcitabine: 1000 mg/m² I. V. on day 1, day 8 and day 15 of every 28 day cycle. Nab-Paclitaxel: 125 mg/m² I. V. on day 1, day 8 and day 15 of every 28 day cycle.
  • Tocilizumab
  • Gemcitabine
  • nab-Paclitaxel
Gemcitabine and nab-PaclitaxelActive ComparatorGemcitabine: 1000 mg/m² I. V. on day 1, day 8 and day 15 of every 28 day cycle. Nab-Paclitaxel: 125 mg/m² I. V. on day 1, day 8 and day 15 of every 28 day cycle.
  • Gemcitabine
  • nab-Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Signed informed consent

          -  Histological or cytological pancreatic adenocarcinoma. Malignant unspecified tumor
             cells in cytological specimen are allowed after investigator assessment, mixed
             histology including adenosquamous carcinoma is allowed

          -  Male or non-pregnant, non-lactating females who are ≥18 years of age at the time of
             signing the informed consent form (ICF)

          -  Non-curable unresectable locally advanced or metastatic pancreatic carcinoma.

          -  A modified Glasgow Prognostic Score (mGPS) criteria of 1 or 2 assessed within 14 days
             of randomization as defined below:

          -  mGPS of 1: CRP > 10 mg/L and albumin ≥ 35 g/L

          -  mGPS of 2: CRP > 10 mg/L and albumin < 35 g/L

          -  No prior antineoplastic chemotherapy or anti-cancer drugs. Patients who have received
             neoadjuvant or adjuvant chemotherapy and who are diagnosed with loco regional
             recurrent or metastatic disease are not eligible

          -  ECOG/WHO Performance Status (PS) 0-1

          -  ≥ 4 weeks since prior major surgery, ≥ 2 weeks since prior minor surgery and ≥ 1 week
             since prior radiation therapy

          -  Measurable disease using the RECIST1.1 criteria, defined as lesions that can be
             measured in at least one dimension and which have not been previously irradiated.
             Longest diameter ≥ 20 mm with conventional techniques or ≥ 10 mm with spiral CT scan
             or MRI

          -  Fertile men and women of childbearing potential (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 [ie, has had menses at any
             time during the preceding 24 consecutive months]) must use secure contraception
             methods as follows: intrauterine device, double-barrier contraception, as a condom and
             occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent
             (foam/gel/cream/suppository), vasectomized partner who is sterile prior to the female
             subject's entry and is the sole sexual partner for that female, or complete abstinence
             from sexual intercourse from before 2 months entering the study until 6 months after
             end of chemotherapy

          -  Acceptable hematology parameters defined as:

          -  Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L

          -  Platelet count ≥ 100 x 10⁹/L

          -  Haemoglobin ≥ 5.6 mmol/L

          -  Acceptable liver function defined as:

          -  Serum bilirubin < 1.5 x upper limit of normal (ULN)

          -  ASAT/ALAT < 2.5 x ULN ( < 5 x ULN with known liver metastasis)

          -  Acceptable renal function with a creatinine clearance ≥ 50 mL/min/ (eg, using the
             Cockroft-Gault formula)

          -  Subjects must have signed and dated a BIOPAC IRB/IEC approved written informed consent
             form in accordance with regulatory and institutional guidelines. This must be obtained
             before the performance of any protocol related procedures that are not part of normal
             subject care

        Exclusion Criteria:

          -  Electrocardiogram (ECG) with significant modifications suggesting a high risk of
             occurrence of angina pectoris or high risk of arrhythmia.

          -  Other malignancies, except adequately treated basal carcinoma or squamous cell
             carcinoma of the skin or in-situ cervix carcinoma or incidental prostate cancer (T1a,
             Gleason score ≤ 6, PSA < 0.5 ng/ml), or any other tumor with a disease free survival
             of ≥ 5 years.

          -  History of serious or concurrent illness or uncontrolled medical disorder; any medical
             condition that might be aggravated by chemotherapy treatment or which could not be
             controlled; including, but not restricted to:

          -  Active infection requiring antibiotics within 2 weeks before the study inclusion

          -  Concurrent congestive heart failure NYHA ( class III - IV )

          -  Unstable angina pectoris, or myocardial infarction within 6 months and/or prior poorly
             controlled hypertension

          -  Inflammatory bowel disease (colitis, Crohns) or other serious gastrointestinal
             conditions associated with risk of perforation

          -  Peripheral neuropathy grade ≥ 2 according to CTCAE v 4.0

          -  Concomitant use of immunosuppressive or myelosuppressive medications that would in the
             opinion of the investigator, increase the risk of serious neutropenic complications.

          -  No known or suspected allergy to the investigational agents or any agents given in
             association with this trial.

          -  Pregnant or lactating women.

          -  Any psychological, familial, sociological, or geographical condition which does not
             permit protocol compliance and medical follow-up.

          -  Enrollment in any other clinical protocol or investigational study with an
             interventional agent or assessments that may interfere with study procedures.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival at 6 months
Time Frame:Approximately up to 6 months.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Performance status at 3 and 6 months assessed by investigator
Time Frame:Approximately up to 6 months.
Safety Issue:
Description:
Measure:Performance status at 3 and 6 months, assessed by patient
Time Frame:Approximately up to 6 months.
Safety Issue:
Description:
Measure:Progression free survival (PFS), defined as the time from the date of randomization until the earliest date of disease progression
Time Frame:Randomization to disease progression, or death due to any cause if sooner. Approximately up to 6 months.
Safety Issue:
Description:
Measure:Overall survival (OS), defined as the time from the date of randomization until death due to any cause.
Time Frame:Randomization until death due to any cause. Approximately up to 12 months.
Safety Issue:
Description:
Measure:Overall response rate (ORR) (ORR = CR + PR), according to RECIST 1.1.RECIST 1.1
Time Frame:Approximately up to 6 months.
Safety Issue:
Description:
Measure:Disease control rate (DCR), (DCR = CR + PR + SD), according to RECIST 1.1.
Time Frame:Approximately up to 6 months.
Safety Issue:
Description:
Measure:Safety (Data on safety parameters) Safety and tolerability of the treatment regimens assessed by a summary of adverse events and clinical laboratory assessments.
Time Frame:Approximately up to 6 months.
Safety Issue:
Description:
Measure:Quality of Life (Quality of Life Questionnaire C30 (QLQ-C30) Version 3.0).
Time Frame:Approximately up to 6 months.
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Herlev Hospital

Last Updated

October 31, 2019