Metastatic Pancreatic CancerPhase 2NCT03502343
Efficacy and Safety of Modified Nab-Paclitaxel Plus Gemcitabine Chemotherapy for Metastatic Pancreatic Cancer
A Phase 2 study testing Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy in people with Metastatic Pancreatic Cancer, run by Yonsei University at 1 site in South Korea.
Trial summary
Recently, a retrospective study reported the efficacy and safety of modified gemcitabine plus nab-paclitaxel (GnP), which were administered biweekly (on days 1 and 15). With 79 patients of metastatic pancreatic cancer, this study reported similar efficacy and improved toxicity profile compared with standard dose GnP… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Metastatic Pancreatic Cancer
- What is being tested?
- Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Apr 2018to Jun 2020
- Phase
- Phase 2
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically or cytologically confirmed pancreatic adenocarcinoma
- Coexisting extrapancreatic distant metastasis
- Older than 19 years old
- Measurable primary tumor in pancreas on imaging study at the time of diagnosis, according to the RECIST criteria
Who cannot join
- Previous history of palliative systemic chemotherapy due to pancreatic cancer
- Existence of active malignancy of other organ which diagnosed in last five years (except the squamous cell carcinoma or basal cell tumor of skin)
- Existence of life-threatening co-morbidity
- Poor performance state (ECOG ≥2)
- Suspected severe bone marrow suppression (Neutrophil count< 1,500/mm3, Hemoglobin< 9 g/dL, Platelet count< 75,000/mm3)
- Suspected severe liver dysfunction (Total bilirubin or Prothrombin Time > 1.5 times of upper normal range) or renal dysfunction (estimated GFR < 50/ml/min/1.73 m²)
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- Pre-existence of ≥grade 2 peripheral sensory neuropathy
- Existence of brain metastasis or meningeal carcinomatosis
- Patient with pregnancy or ongoing breast feeding
- Do not agree with the informed consent
Trial locations and contacts
1 site in 1 country.
South Korea1 site, 1 recruiting
- Recruiting
Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine
Seoul, 03722
Seungmin Bang, MD, Ph.D, 02-2228-1995, Bang7028@yuhs.ac
About this study
Official title: Efficacy and Safety of Modified Nab-Paclitaxel Plus Gemcitabine Chemotherapy for Metastatic Pancreatic Cancer: A Single-arm Phase II Clinical Trial
Recently, a retrospective study reported the efficacy and safety of modified gemcitabine plus nab-paclitaxel (GnP), which were administered biweekly (on days 1 and 15). With 79 patients of metastatic pancreatic cancer, this study reported similar efficacy and improved toxicity profile compared with standard dose GnP (OS 10 months, PFS 5.4 months, Grade ≥3 Neutropenia 19%, Grade ≥3 sensory neuropathy 1.6%). Also, several studies reported that dose reduction of nab-paclitaxel in breast or pancreatic cancer treatment was not related of decreased survival, or related with prolonged survival and increased treatment exposure. However, this finding need to be evaluated in prospective clinical trial.
This phase II trial will evaluate the efficacy and safety of modified GnP, which omit the day 8 administration of nab-paclitaxel, in metastatic pancreatic cancer.
Read the detailed description
Gemcitabine-based combination therapy have been used to prolong survival for patient with pancreatic cancer. In early 2010s, gemcitabine plus nab-paclitaxel (GnP) combination regimen have been introduced based on the results of randomized phase III clinical trial that showed survival benefit than gemcitabine monotherapy. Nab-paclitaxel is a nanoparticle albumin-bound paclitaxel that showed anti-tumor activity as well as synergistic effect in combination with gemcitabine.
In the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), the maximal tolerated nab-paclitaxel dose (125 mg/m2) was administrated with 1000 mg/m2 of gemcitabine, on days 1, 8 and 15 for 4 weeks cycle. This combination therapy showed favorable treatment response, but notable severe adverse events were also reported. Grade 3 or higher neuropathy and neutropenia occurred in 17% and 38% of patients, respectively. Also, dose reduction was required in approximately half of the patients.
Recently, a retrospective study reported the efficacy and safety of modified GnP, which were administered biweekly (on days 1 and 15). With 79 patients of metastatic pancreatic cancer, this study reported similar efficacy and improved toxicity profile compared with standard dose GnP (OS 10 months, PFS 5.4 months, Grade ≥3 Neutropenia 19%, Grade ≥3 sensory neuropathy 1.6%). Also, several studies reported that dose reduction of nab-paclitaxel in breast or pancreatic cancer treatment was not related of decreased survival, or related with prolonged survival and increased treatment exposure. However, this finding need to be evaluated in prospective clinical trial.
This phase II trial will evaluate the efficacy and safety of modified GnP, which omit the day 8 administration of nab-paclitaxel, in metastatic pancreatic cancer.
- Conditions
- Metastatic Pancreatic Cancer
- Being tested
- Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy
- Keywords
- Pancreatic cancer, Metastatic, Modified, Gemcitabine, nab-Paclitaxel
- Medical subject headings
- Pancreatic Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modified Gemcitabine plus nab-Paclitaxel Combination ChemotherapyDrug
All patients will receive slow (over 30-40 minutes) intravenous administration of nab-paclitaxel (125 mg/m2) on days 1 and 15, and gemcitabine (1000 mg/m2) on days 1, 8, and 15 of a 28- day cycle (every 4 weeks). Treatment will discontinue if disease progression or intolerable toxicity is observed, if the patient withdraws from the study, or at the physician's discretion.
Dose reduction of the chemotherapeutic agent and/or delay of administration is allowed if serious treatment-related AEs occur, according to specified guideline in study protocol (Level 1: 100% -> 80%; Level 2: 80% -> 60%). If dose reduction is needed more than Level 2, the patient will be dropped from the trial.
| Study group | Role | What they receive |
|---|---|---|
| Modified Gemcitabine plus nab-Paclitaxel | Experimental | The intervention group Receives: Drug: Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate
To evaluate treatment efficacy, computed tomography scan, magnetic resonance imaging, or 18F-fluorodeoxyglucose-positron emission tomography (18F-FDGPET) scan will be performed every 8 weeks. Treatment responses according to the RECIST criteria will be reported by designated radiologists and final disease assessment will be independently made by the attending physician. The proportion of patients with the best response of complete response (CR), partial response (PR) is defined as objective response rate.
Measured: Every 8 weeks until dropout up to 104 weeks
Disease control rate
To evaluate treatment efficacy, computed tomography scan, magnetic resonance imaging, or 18F-fluorodeoxyglucose-positron emission tomography (18F-FDGPET) scan will be performed every 8 weeks. Disease control rate is defined as the proportion of patients with the best response of CR, PR and stable disease.
Measured: Every 8 weeks until dropout up to 104 weeks
Secondary outcomes (3)
Overall survival
The overall survival is defined as from the date of enrollment to the date of the last follow-up or death of all causes. In case of loss of follow-up, the censoring date will be the day on which the survival is confirmed before follow-up loss.
Measured: Every 8 weeks from date of drug administration until the date of patient's death, loss of follow-up, or end of the trial up to 104 weeks
Progression-free survival
The progression free survival is defined as from the date of treatment initiation to the date of the event. The event is defined as the date of disease progression or patient's death, which occured first.
In case of loss of follow-up, the censoring date will be the day on which the survival is confirmed before follow-up loss.
Measured: Every 8 weeks from date of drug administration until the date of patient's death, loss of follow-up, or end of the trial up to 104 weeks
Adverse event
Adverse events will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03) before each cycle until study dropout.
Measured: Until dropout from the trial up to 104 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2018
- Study start1 Apr 2018
- Primary completionApr 2020 (estimated)
- Study completionJun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Metastatic Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03502343
- Sponsor's protocol ID
- 4-2017-0840
- Status last verified
- Apr 2018
- First submitted
- 3 Apr 2018
- Last updated
- 18 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.
PubMed 24131140Ahn DH, Krishna K, Blazer M, Reardon J, Wei L, Wu C, Ciombor KK, Noonan AM, Mikhail S, Bekaii-Saab T. A modified regimen of biweekly gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer is both tolerable and effective: a retrospective analysis. Ther Adv Med Oncol. 2017 Feb;9(2):75-82. doi: 10.1177/1758834016676011. Epub 2016 Nov 2.
PubMed 28203300Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P, McGuire JR, Iglesias J. Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: final analysis of overall survival. Clin Breast Cancer. 2012 Oct;12(5):313-21. doi: 10.1016/j.clbc.2012.05.001. Epub 2012 Jun 23.
PubMed 22728026Scheithauer W, Ramanathan RK, Moore M, Macarulla T, Goldstein D, Hammel P, Kunzmann V, Liu H, McGovern D, Romano A, Von Hoff DD. Dose modification and efficacy of nab-paclitaxel plus gemcitabine vs. gemcitabine for patients with metastatic pancreatic cancer: phase III MPACT trial. J Gastrointest Oncol. 2016 Jun;7(3):469-78. doi: 10.21037/jgo.2016.01.03.
PubMed 27284481
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Modified Nab-Paclitaxel Plus Gemcitabine Chemotherapy for Metastatic Pancreatic Cancer: A Single-arm Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT03502343
- Acronym / sponsor ID
- 4-2017-0840
- Conditions
- Metastatic Pancreatic Cancer
- Keywords
- Pancreatic cancer, Metastatic, Modified, Gemcitabine, nab-Paclitaxel
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 1 Apr 2018 (actual)
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Jun 2020 (estimated)
- First posted
- 18 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recently, a retrospective study reported the efficacy and safety of modified gemcitabine plus nab-paclitaxel (GnP), which were administered biweekly (on days 1 and 15). With 79 patients of metastatic pancreatic cancer, this study reported similar efficacy and improved toxicity profile compared with standard dose GnP (OS 10 months, PFS 5.4 months, Grade ≥3 Neutropenia 19%, Grade ≥3 sensory neuropathy 1.6%). Also, several studies reported that dose reduction of nab-paclitaxel in breast or pancreatic cancer treatment was not related of decreased survival, or related with prolonged survival and increased treatment exposure. However, this finding need to be evaluated in prospective clinical trial.
This phase II trial will evaluate the efficacy and safety of modified GnP, which omit the day 8 administration of nab-paclitaxel, in metastatic pancreatic cancer.
Detailed description
Gemcitabine-based combination therapy have been used to prolong survival for patient with pancreatic cancer. In early 2010s, gemcitabine plus nab-paclitaxel (GnP) combination regimen have been introduced based on the results of randomized phase III clinical trial that showed survival benefit than gemcitabine monotherapy. Nab-paclitaxel is a nanoparticle albumin-bound paclitaxel that showed anti-tumor activity as well as synergistic effect in combination with gemcitabine.
In the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), the maximal tolerated nab-paclitaxel dose (125 mg/m2) was administrated with 1000 mg/m2 of gemcitabine, on days 1, 8 and 15 for 4 weeks cycle. This combination therapy showed favorable treatment response, but notable severe adverse events were also reported. Grade 3 or higher neuropathy and neutropenia occurred in 17% and 38% of patients, respectively. Also, dose reduction was required in approximately half of the patients.
Recently, a retrospective study reported the efficacy and safety of modified GnP, which were administered biweekly (on days 1 and 15). With 79 patients of metastatic pancreatic cancer, this study reported similar efficacy and improved toxicity profile compared with standard dose GnP (OS 10 months, PFS 5.4 months, Grade ≥3 Neutropenia 19%, Grade ≥3 sensory neuropathy 1.6%). Also, several studies reported that dose reduction of nab-paclitaxel in breast or pancreatic cancer treatment was not related of decreased survival, or related with prolonged survival and increased treatment exposure. However, this finding need to be evaluated in prospective clinical trial.
This phase II trial will evaluate the efficacy and safety of modified GnP, which omit the day 8 administration of nab-paclitaxel, in metastatic pancreatic cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Modified Gemcitabine plus nab-Paclitaxel | Experimental | Drug: Modified Gemcitabine plus nab-Paclitaxel Combination ChemotherapyThe intervention group |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Pathologically or cytologically confirmed pancreatic adenocarcinoma
- Coexisting extrapancreatic distant metastasis
- Older than 19 years old
- Measurable primary tumor in pancreas on imaging study at the time of diagnosis, according to the RECIST criteria
Key exclusion criteria (10 listed)
- Previous history of palliative systemic chemotherapy due to pancreatic cancer
- Existence of active malignancy of other organ which diagnosed in last five years (except the squamous cell carcinoma or basal cell tumor of skin)
- Existence of life-threatening co-morbidity
- Poor performance state (ECOG ≥2)
- Suspected severe bone marrow suppression (Neutrophil count< 1,500/mm3, Hemoglobin< 9 g/dL, Platelet count< 75,000/mm3)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modified Gemcitabine plus nab-Paclitaxel Combination ChemotherapyAll patients will receive slow (over 30-40 minutes) intravenous administration of nab-paclitaxel (125 mg/m2) on days 1 and 15, and gemcitabine (1000 mg/m2) on days 1, 8, and 15 of a 28- day cycle (every 4 weeks). Treatment will discontinue if disease progression or intolerable toxicity is observed, if the patient withdraws from the study, or at the physician's discretion. Dose reduction of the chemotherapeutic agent and/or delay of administration is allowed if serious treatment-related AEs occur, according to specified guideline in study protocol (Level 1: 100% -> 80%; Level 2: 80% -> 60%). If dose reduction is needed more than Level 2, the patient will be dropped from the trial. | Drug | Modified Gemcitabine plus nab-Paclitaxel |
Primary outcome
Objective response rate
Time frame: Every 8 weeks until dropout up to 104 weeks
To evaluate treatment efficacy, computed tomography scan, magnetic resonance imaging, or 18F-fluorodeoxyglucose-positron emission tomography (18F-FDGPET) scan will be performed every 8 weeks. Treatment responses according to the RECIST criteria will be reported by designated radiologists and final disease assessment will be independently made by the attending physician. The proportion of patients with the best response of complete response (CR), partial response (PR) is defined as objective response rate.
Disease control rate
Time frame: Every 8 weeks until dropout up to 104 weeks
To evaluate treatment efficacy, computed tomography scan, magnetic resonance imaging, or 18F-fluorodeoxyglucose-positron emission tomography (18F-FDGPET) scan will be performed every 8 weeks. Disease control rate is defined as the proportion of patients with the best response of CR, PR and stable disease.
3 secondary outcomes
Overall survival
Time frame: Every 8 weeks from date of drug administration until the date of patient's death, loss of follow-up, or end of the trial up to 104 weeks
Progression-free survival
Time frame: Every 8 weeks from date of drug administration until the date of patient's death, loss of follow-up, or end of the trial up to 104 weeks
Adverse event
Time frame: Until dropout from the trial up to 104 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2018.
- Background: PubMed 24131140Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.
- Background: PubMed 28203300Ahn DH, Krishna K, Blazer M, Reardon J, Wei L, Wu C, Ciombor KK, Noonan AM, Mikhail S, Bekaii-Saab T. A modified regimen of biweekly gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer is both tolerable and effective: a retrospective analysis. Ther Adv Med Oncol. 2017 Feb;9(2):75-82. doi: 10.1177/1758834016676011. Epub 2016 Nov 2.
- Background: PubMed 22728026Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P, McGuire JR, Iglesias J. Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: final analysis of overall survival. Clin Breast Cancer. 2012 Oct;12(5):313-21. doi: 10.1016/j.clbc.2012.05.001. Epub 2012 Jun 23.
- Background: PubMed 27284481Scheithauer W, Ramanathan RK, Moore M, Macarulla T, Goldstein D, Hammel P, Kunzmann V, Liu H, McGovern D, Romano A, Von Hoff DD. Dose modification and efficacy of nab-paclitaxel plus gemcitabine vs. gemcitabine for patients with metastatic pancreatic cancer: phase III MPACT trial. J Gastrointest Oncol. 2016 Jun;7(3):469-78. doi: 10.21037/jgo.2016.01.03.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine
Seoul, South Korea
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy in people with Metastatic Pancreatic Cancer, run by Yonsei University at 1 site in South Korea.
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 4 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 18 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (time frame: Every 8 weeks until dropout up to 104 weeks). The study lists 2 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 NCT03502343, which also lists 4 linked publications.
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 18 Apr 2018.