Metastatic Pancreatic Cancer
Conditions
Keywords
pancreatic cancer
Brief summary
The main objective of this trial is to evaluate every 2 months alternating nab-paclitaxel/gemcitabine and FOLFIRI.3 versus nab-paclitaxel + gemcitabine, regarding the progression of disease at 6 months.
Interventions
DRUGFOLFIRI.3
For each cycle : 1 week out of 2 - injection at Day1, J15 Irinotécan 90 mg/m² at day1 in perfusion over 60 min in Y of folinic acid Folinic Acid 400 mg/m² (or 200 mg/m² Elvorine) at Day 1 in perfusion over 2 hours 5FU continu 2000 mg/m² during 46 hours Irinotécan at 90 mg/m² in perfusion over 60 mn at Day 3 (when 5FU perfusion is over)
DRUGnab-paclitaxel+ gemcitabine
For each cycle : 3 weeks out of 4 - injection at Day 1, 8 and 15 Nab-paclitaxel : 125 mg/m² of nab-paclitaxel in perfusion over 30 mn. Gemcitabine 1000 mg/m² in perfusion over 30 mn immediately after Nab paclitaxel administration is over.
Sponsors
UNICANCER
GERCOR - Multidisciplinary Oncology Cooperative Group
Federation Francophone de Cancerologie Digestive
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histological or cytological confirmation of pancreatic adenocarcinoma * Distant metastatic disease * Scan (or MRI if scanner contraindicated) completed within 3 weeks of the start of treatment * At least one lesion measurable by RECIST v1.1 criteria * Life expectancy\> 3 months * No previous chemotherapy (adjuvant chemotherapy with gemcitabine authorised if administered more than 6 months prior to inclusion) * No previous radiotherapy (unless at least one measurable target lesion outside the irradiation zone) * Pain must be monitored before inclusion * 18 years \< age \< 75 * Performance status: WHO \< 2 * ANC ≥ 1500/mm3, platelets ≥ 100 000/mm3, haemoglobin ≥ 9 g/dL * ASAT (SGOT), ALAT (SGPT) ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases found * Bilirubin ≤ 1.5 x ULN (patients drained by retrograde technique are includable), creatinine \< 120 μmol/L, or MDRD creatinine clearance \> 60 mL/min * Women of childbearing age must have a negative pregnancy test (β HCG) before starting treatment * Women of childbearing age as well as men (who have sexual intercourse with women of childbearing age) must agree to use effective contraception without interruption for the duration of treatment and 6 months after the administration of the last treatment dose * Patient affiliated to the social security scheme * Patient information and signature of informed consent
Exclusion criteria
* \- Other types of pancreatic tumours, especially endocrine or acinar cell tumours * Ampulloma * Presence of meningeal or cerebral metastases, bone metastases * Gilbert's syndrome * Presence of neuropathy\> grade 1 according to NCIC-CTC 4.0 * Contraindications specific to the studied treatments * History of chronic diarrhoea or inflammatory disease of the colon or rectum, or of unresolved occlusion or sub-occlusion for which symptomatic treatment is being administered * Other concomitant cancer or history of cancer during the 5 years, with the exception of a carcinoma in situ of the cervix or basal cell or squamous cell carcinoma, considered cured * Significant history of heart or respiratory disease, including any history of interstitial pneumonia * Patient already included in another clinical trial with an experimental molecule * Women who are breast-feeding * Persons deprived of liberty or under guardianship * Unable to submit to medical monitoring during the trial due to geographical, social or psychological reasons
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Alive and Without Radiological and/or Clinical Progression 6 Months After the Randomization | 6 months after randomization | The primary endpoint was the rate of patients alive and progression-free 6 months after randomization. Progression was assessed by the investigator and defined radiologically according to RECIST v1.1 criteria and/or clinically as deterioration of general condition not related to treatment, palpable tumor masses on clinical examination (adenopathy, tumor hepatomegaly, peritoneal carcinosis), pleural effusion, ascites. Patients who progressed or died before 6 months were considered to have failed the primary endpoint at 6 months. The 6-month imaging was the imaging done at 6 months with a +/- 1 month window. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS): | Up to 2 years after the treatment start | Overall survival was defined as the time from the date of randomization to the patient's death (all causes). For alive patients, the date of last news was taken into account |
| Best Response | Up to the end of treatment on the average of 12 months | Best response is defined as the best response for each patient regarding imagerie taken during the treatment. Response was evalauted according to RECIST v1.1 over the entire treatment period according the investigator |
| Progression-free Survival (PFS) | up to 12 months after randomization | It was defined as the time between t randomization and the date of the first radiological progression (RECIST 1.1 criteria) and/or clinical progression according to the investigator or death (whatever the cause is); Patients alive without progression were censored at date of last news |
Countries
France
Participant flow
Recruitment details
Between November 2015 and November 2016, 127 patients were enrolled in the trial by 36 french centres .
Participants by arm
| Arm | Count |
|---|---|
| Nab-paclitaxel + Gemcitabine/FOLFIRI.3 Alternance of :
* 2 months with nab-paclitaxel (125 g/m² - 30 min in IV) + gemcitabine (1000 mg/m², 30 min in IV, 3 injections follow by 1 week free)
* follow by 2 months with FOLFIRI.3 (irinotecan: 90 mg/m² at D1, acid folinic 400 mg/m², 5Fu continus: 2000 mg/m² IV 46 hours, and irinotecan at D3, 90 mg/m²) This alternance continus until progression
FOLFIRI.3: For each cycle : 1 week out of 2 - injection at Day1, J15 Irinotécan 90 mg/m² at day1 in perfusion over 60 min in Y of folinic acid Folinic Acid 400 mg/m² (or 200 mg/m² Elvorine) at Day 1 in perfusion over 2 hours 5FU continu 2000 mg/m² during 46 hours Irinotécan at 90 mg/m² in perfusion over 60 mn at Day 3 (when 5FU perfusion is over)
nab-paclitaxel+ gemcitabine: For each cycle : 3 weeks out of 4 - injection at Day 1, 8 and 15 Nab-paclitaxel : 125 mg/m² of nab-paclitaxel in perfusion over 30 mn. Gemcitabine 1000 mg/m² in perfusion over 30 mn immediately after Nab paclitaxel administration is over. | 64 |
| Nab-paclitaxel + Gemcitabine nab-paclitaxel (125 g/m² - 30 min in IV) + gemcitabine (1000 mg/m² - 30 min in IV) 3 injections follow by 1 week free, until progression
nab-paclitaxel+ gemcitabine: For each cycle : 3 weeks out of 4 - injection at Day 1, 8 and 15 Nab-paclitaxel : 125 mg/m² of nab-paclitaxel in perfusion over 30 mn. Gemcitabine 1000 mg/m² in perfusion over 30 mn immediately after Nab paclitaxel administration is over. | 63 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 2 |
| Overall Study | Patients not treated | 1 | 1 |
Baseline characteristics
| Characteristic | Nab-paclitaxel + Gemcitabine | Total | Nab-paclitaxel + Gemcitabine/FOLFIRI.3 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 33 Participants | 67 Participants | 34 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 60 Participants | 30 Participants |
| Age, Continuous | 65.99 years | 65.33 years | 65.20 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 63 Participants | 127 Participants | 64 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment France | 63 participants | 127 participants | 64 participants |
| Sex: Female, Male Female | 34 Participants | 62 Participants | 28 Participants |
| Sex: Female, Male Male | 29 Participants | 65 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 53 / 64 | 54 / 63 |
| other Total, other adverse events | 63 / 64 | 58 / 58 |
| serious Total, serious adverse events | 30 / 64 | 19 / 58 |
Outcome results
Primary
Percentage of Patients Alive and Without Radiological and/or Clinical Progression 6 Months After the Randomization
The primary endpoint was the rate of patients alive and progression-free 6 months after randomization. Progression was assessed by the investigator and defined radiologically according to RECIST v1.1 criteria and/or clinically as deterioration of general condition not related to treatment, palpable tumor masses on clinical examination (adenopathy, tumor hepatomegaly, peritoneal carcinosis), pleural effusion, ascites. Patients who progressed or died before 6 months were considered to have failed the primary endpoint at 6 months. The 6-month imaging was the imaging done at 6 months with a +/- 1 month window.
Time frame: 6 months after randomization
Population: The primary endpoint was analysed on the mITT population meaning all the randomized patients with at least one dose of study drug taken
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nab-paclitaxel + Gemcitabine/FOLFIRI.3 | Percentage of Patients Alive and Without Radiological and/or Clinical Progression 6 Months After the Randomization | 28 Participants |
| Nab-paclitaxel + Gemcitabine | Percentage of Patients Alive and Without Radiological and/or Clinical Progression 6 Months After the Randomization | 14 Participants |
Secondary
Best Response
Best response is defined as the best response for each patient regarding imagerie taken during the treatment. Response was evalauted according to RECIST v1.1 over the entire treatment period according the investigator
Time frame: Up to the end of treatment on the average of 12 months
Population: Endpoint was analysed on mITT population meaning all randomized patients having at least one dose of treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nab-paclitaxel + Gemcitabine/FOLFIRI.3 | Best Response | Partial Response | 24 Participants |
| Nab-paclitaxel + Gemcitabine/FOLFIRI.3 | Best Response | Progression | 5 Participants |
| Nab-paclitaxel + Gemcitabine/FOLFIRI.3 | Best Response | Stability | 20 Participants |
| Nab-paclitaxel + Gemcitabine/FOLFIRI.3 | Best Response | Death without any imagery | 12 Participants |
| Nab-paclitaxel + Gemcitabine/FOLFIRI.3 | Best Response | Complete response | 1 Participants |
| Nab-paclitaxel + Gemcitabine | Best Response | Death without any imagery | 5 Participants |
| Nab-paclitaxel + Gemcitabine | Best Response | Complete response | 0 Participants |
| Nab-paclitaxel + Gemcitabine | Best Response | Partial Response | 16 Participants |
| Nab-paclitaxel + Gemcitabine | Best Response | Stability | 26 Participants |
| Nab-paclitaxel + Gemcitabine | Best Response | Progression | 13 Participants |
Secondary
Overall Survival (OS):
Overall survival was defined as the time from the date of randomization to the patient's death (all causes). For alive patients, the date of last news was taken into account
Time frame: Up to 2 years after the treatment start
Population: Endpoint was analyzed on the ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-paclitaxel + Gemcitabine/FOLFIRI.3 | Overall Survival (OS): | 11.71 months |
| Nab-paclitaxel + Gemcitabine | Overall Survival (OS): | 10.94 months |
Secondary
Progression-free Survival (PFS)
It was defined as the time between t randomization and the date of the first radiological progression (RECIST 1.1 criteria) and/or clinical progression according to the investigator or death (whatever the cause is); Patients alive without progression were censored at date of last news
Time frame: up to 12 months after randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-paclitaxel + Gemcitabine/FOLFIRI.3 | Progression-free Survival (PFS) | 5.72 months |
| Nab-paclitaxel + Gemcitabine | Progression-free Survival (PFS) | 4.21 months |