Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab in Pancreatic Cancer Patients (PACTO)
Primary Purpose
Unresectable Pancreatic Carcinoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tocilizumab
Gemcitabine
nab-Paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Unresectable Pancreatic Carcinoma
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.
Sites / Locations
- Herlev & Gentofte University Hospital, Denmark
- Department of Oncology
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tocilizumab & Gemcitabine and nab-Paclitaxel
Gemcitabine and nab-Paclitaxel
Arm Description
Tocilizumab: 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.
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.
Outcomes
Primary Outcome Measures
Overall survival at 6 months
Secondary Outcome Measures
Performance status at 3 and 6 months assessed by investigator
Performance status at 3 and 6 months, assessed by patient
Progression free survival (PFS), defined as the time from the date of randomization until the earliest date of disease progression
Overall survival (OS), defined as the time from the date of randomization until death due to any cause.
Overall response rate (ORR) (ORR = CR + PR), according to RECIST 1.1.RECIST 1.1
Disease control rate (DCR), (DCR = CR + PR + SD), according to RECIST 1.1.
Safety (Data on safety parameters) Safety and tolerability of the treatment regimens assessed by a summary of adverse events and clinical laboratory assessments.
Quality of Life (Quality of Life Questionnaire C30 (QLQ-C30) Version 3.0).
Full Information
NCT ID
NCT02767557
First Posted
May 6, 2016
Last Updated
September 21, 2023
Sponsor
Herlev Hospital
Collaborators
Celgene
1. Study Identification
Unique Protocol Identification Number
NCT02767557
Brief Title
Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab in Pancreatic Cancer Patients
Acronym
PACTO
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.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
January 26, 2017 (Actual)
Primary Completion Date
August 12, 2021 (Actual)
Study Completion Date
January 1, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Herlev Hospital
Collaborators
Celgene
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unresectable Pancreatic Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
147 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tocilizumab & Gemcitabine and nab-Paclitaxel
Arm Type
Experimental
Arm Description
Tocilizumab:
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.
Arm Title
Gemcitabine and nab-Paclitaxel
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
(ACTEMRA®)
Intervention Description
Intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Intravenous infusion
Intervention Type
Drug
Intervention Name(s)
nab-Paclitaxel
Other Intervention Name(s)
ABRAXANE®
Intervention Description
Intravenous infusion,
Primary Outcome Measure Information:
Title
Overall survival at 6 months
Time Frame
Approximately up to 6 months.
Secondary Outcome Measure Information:
Title
Performance status at 3 and 6 months assessed by investigator
Time Frame
Approximately up to 6 months.
Title
Performance status at 3 and 6 months, assessed by patient
Time Frame
Approximately up to 6 months.
Title
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.
Title
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.
Title
Overall response rate (ORR) (ORR = CR + PR), according to RECIST 1.1.RECIST 1.1
Time Frame
Approximately up to 6 months.
Title
Disease control rate (DCR), (DCR = CR + PR + SD), according to RECIST 1.1.
Time Frame
Approximately up to 6 months.
Title
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.
Title
Quality of Life (Quality of Life Questionnaire C30 (QLQ-C30) Version 3.0).
Time Frame
Approximately up to 6 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Inna Chen, MD
Organizational Affiliation
Herlev & Gentofte Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Olav Dajani, MD PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Herlev & Gentofte University Hospital, Denmark
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Department of Oncology
City
Oslo
ZIP/Postal Code
0424
Country
Norway
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab in Pancreatic Cancer Patients
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