Efficacy and Tolerance Evaluation in FOLFIRINOX Dose Adjusted in Elderly Patients With a Metastatic Pancreatic Cancer (PAMELA70)
Primary Purpose
Pancreatic Metastatic Cancer, Toxicity
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Oxaliplatine
Folinic acid
Irinotecan
5-FU
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Metastatic Cancer focused on measuring Pancreatic metastatic cancer, FOLFIRINOX, toxicity, efficacy
Eligibility Criteria
Inclusion Criteria:
- Histologically proven ductal pancreatic carcinoma
- Metastatic disease
- First-line treatment : No previous chemotherapy in metastatic stage but adjuvant treatment before relapse (secondary metastatic) is permitted, provide it has been administered more than 6 months before)
- Age of 70 yo or above
- Normal DPD enzyme level or partial defect (excluding total defect)
- Adequate bone marrow reserve: as indicated by : neutrophils >1500/mm3, platelets >100,000/ mm3, Hb >10.0g/dL.
- Adequate Renal function as indicated by: MDRD creatinine clearance > 50ml/min.
- Adequate hepatic function as indicated by: serum bilirubin < 1.5 times the upper limit of normal, AST and ALT < 2.5 times the upper limit of normal, or < 5 times the upper limit of normal if liver metastases are present.
- Written informed consent must be obtained prior to protocol-specific procedures are being performed
- Patient is affiliated to a social security category
Exclusion Criteria:
- Other than ductal pancreatic carcinoma: namely endocrin tumors, acinar cells carcinoma, cystadenocarcinoma or adenocarcinoma of the ampulla of vater
- Non-metastatic but locally advanced pancreatic adenocarcinoma
- Complete DPD deficiency
- History of Cardiac failure or symptomatic coronary artery disease
- Autonomy Daily Living score by Katz <4
- Prior treatment with FOLFIRINOX (adjuvant)
- Major comorbidity likely to be an obstacle to treatment
- Active or uncontrolled infection such as HIV or chronic B or C hepatitis
- Uncontrolled diabetes mellitus
- Prior peripheral neuropathy, grade > 2
- Inflammatory bowel disease localized on the colon or rectum; bowel obstruction or severe uncontrolled diarrhea
- Previous or concomitant malignancies other than effectively treated carcinoma in situ of the cervix or non-melanoma skin cancer
- Hereditary fructose intolerance
- Persons deprived of liberty or under guardianship
- Any social, geographical or psychological condition which would compromise the ability to fully comply with the trial procedures and treatments
Sites / Locations
- ICO Paul Papin
- CH Vendée
- Centre Oscar Lambret
- ICM (Val d'Aurelle)
- Centre Eugène marquis
- ICO René Gauducheau
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
FOLFIRINOX
Arm Description
FOLFIRINOX (D1-D15, for maximum 12 cycles) = Oxaliplatine + Folinic acid + Irinotecan + 5-FU
Outcomes
Primary Outcome Measures
1st step analysis : Safety and efficacy after 34 patients included
Evaluation of Efficacy: Progression-free-Survival (PFS) and Overall Survival (OS) will be evaluated.
Evaluation of Toxicity: Will be analyzed, according to the NCI-CTCAE version 4.0:
The incidence of hematological toxicities (grade 3-4, in particular neutropenia and febrile neutropenia)
The incidence of GI toxicities, in particular diarrhea and oral mucositis
The incidence of peripheral neuropathies
For statistical analysis :
either >= 17 patients show a decrease of their ADL (of 1.5 ADL or more) : the treatment is considered as being too toxic, either <= 3 patients presented a tumoral response: the treatment is considered as not being effective enough,
=> The study will then be arrested in this 1st stage.
Secondary Outcome Measures
2nd step analysis : Safety and efficacy after 72patients included
Only if 1st step is successful we can do the second step :
For toxicity : if >= 31patients show a decrease of their ADL (of 1.5 ADL or more) and/or
For efficacy : if <= 10 patients presented a tumoral response
=> Study is successful if :
we obtain at least 11 tumoral response and
maximum 30 patients on 72 evaluable are in loss of autonomy (ADL)
Full Information
NCT ID
NCT02143219
First Posted
May 14, 2014
Last Updated
July 26, 2022
Sponsor
Institut Cancerologie de l'Ouest
1. Study Identification
Unique Protocol Identification Number
NCT02143219
Brief Title
Efficacy and Tolerance Evaluation in FOLFIRINOX Dose Adjusted in Elderly Patients With a Metastatic Pancreatic Cancer
Acronym
PAMELA70
Official Title
Phase-2 Study Evaluating Overall Response Rate (Efficacy) and Autonomy Daily Living Preservation (Tolerance) of "FOLFIRINOX " Pharmacogenetic Dose Adjusted, in Elderly Patients (70 yo. or Older) With a Metastatic Pancreatic Adenocarcinoma.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
July 31, 2014 (Actual)
Primary Completion Date
November 25, 2020 (Actual)
Study Completion Date
November 25, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Cancerologie de l'Ouest
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Metastatic pancreatic carcinomas represent the 5th cause of cancer death in France (#8000 per year). The median age at diagnosis is 69 and 74 in male and female respectively. When the 5-Fluorouracile has been used as a single agent with a limited efficacy during more than 20 years, the onset of gemcitabine in 1995 has led to a moderate increase of median survival (from 4.41 to 5.65 months) and overall survival at 1 year (2 versus 18%). Recently, in a phase II followed by a phase-III study, a French collaborative group has demonstrated the benefit of "FOLFIRINOX " regimen versus gemcitabine alone, in terms of median survival (11.1 versus 6.8 months), progression-free survival (6.4 versus 3.3 months) and response rate (31.6 versus 9.4%).
Although more hematologic (neutropenia) and GI toxicities were observed, FOLFIRINOX was acceptable as a new standard regimen for the majority of patients under the age of 70 with a good Performans Status. To reduce the toxicity of FOLFIRINOX in elderly patients (> 70 yo), pharmacogenetic monitoring of 5-FU and Irinotecan key metabolism enzymes (DPD and UGTA1) may be easily performed. The methodology of the study is to use the Bryant & Day statistical method, allowing to consider simultaneously as principal objective, the response rate (efficacy) and the tolerance (preservation of autonomy daily living, Katz index): this design is particularly fitting in a study for elderly patients who represent half of the pancreatic carcinoma population.
Detailed Description
METHODOLOGY :
Phase II study, opened, multicentric
MAIN OBJECTIVE :
The main objective is the simultaneous evaluation of the objective rate of answer and toxicity of her(it) of the protocol FOLFIRINOX administered to doses adapted at patients of 70 and more years old.
SECONDARY OBJECTIVE :
Efficiency evaluation;
Tolerance evaluation;
Quality of Life (QoL) and clinical profit.
STATISTICAL ANALYSIS:
An analysis in two stages is planned, according to the method of Bryant and Day with a risk ß 5 % to reject wrongly an effective treatment and of acceptable toxicity and a risk a=10 % to accept wrongly a not rather effective or too toxic treatment.
The study will be considered as successful if:
we obtain at least 11 tumoral answers and
maxi 30 patients on 72 are in loss of autonomy (decrease of their ADL).
All the patients who will have received at least an injection will be eligible for the evaluation of the toxicity
The evaluation of the efficiency will be made after 3 cures at least unless early termination where the scanner will be anticipated.
All the toxicity will be increased according to criteria of toxicity NCI-CTC v4.0.
The evaluation of the tumoral answer (CR, PR and SD) will be made according to the criteria RECIST-v1.1.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Metastatic Cancer, Toxicity
Keywords
Pancreatic metastatic cancer, FOLFIRINOX, toxicity, efficacy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FOLFIRINOX
Arm Type
Other
Arm Description
FOLFIRINOX (D1-D15, for maximum 12 cycles) = Oxaliplatine + Folinic acid + Irinotecan + 5-FU
Intervention Type
Drug
Intervention Name(s)
Oxaliplatine
Other Intervention Name(s)
Eloxatine®
Intervention Description
Oxaliplatine : 85mg/m², 2-hours IV infusion (D1),
Intervention Type
Drug
Intervention Name(s)
Folinic acid
Intervention Description
Folinic acid (FA): 400 mg/m² , 2-hour IV infusion (D1),
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Campto®
Intervention Description
Irinotecan (at the dosage determined by the UGT1A1 status), 90 min IV infusion starting 30 min after the FA starts
Homozygous 6/6 or 6/7: irinotecan will start at 150 mg/m², then will be increased according to clinical/biological tolerance by 10% steps, at each cycle, up to 180 mg/m² at max.
Homozygous 7/7: irinotecan will start at 130 mg/m² in the first cycle then be increased up to a max of 150 mg/m², by 10% steps, according to tolerance.
Intervention Type
Drug
Intervention Name(s)
5-FU
Other Intervention Name(s)
5-fluorouracile
Intervention Description
5-FU (according to the DPD pharmacogenetic status), continuous IV infusion of 46 hours, starting at the end of FA infusion:
If no DPD deficiency, 5-FU start at 1600 mg/m² and can be modulated according to clinical/biological tolerance after each course, i.e., 1800 mg/m² the 2nd course and 2000 mg/m² the 3rd one
If partial DPD deficiency: 5-FU start at 1200 mg/m² and can be increased up to 1800, then 2000 if the clinical/biological tolerance are good at the 2nd and 3rd course.
Primary Outcome Measure Information:
Title
1st step analysis : Safety and efficacy after 34 patients included
Description
Evaluation of Efficacy: Progression-free-Survival (PFS) and Overall Survival (OS) will be evaluated.
Evaluation of Toxicity: Will be analyzed, according to the NCI-CTCAE version 4.0:
The incidence of hematological toxicities (grade 3-4, in particular neutropenia and febrile neutropenia)
The incidence of GI toxicities, in particular diarrhea and oral mucositis
The incidence of peripheral neuropathies
For statistical analysis :
either >= 17 patients show a decrease of their ADL (of 1.5 ADL or more) : the treatment is considered as being too toxic, either <= 3 patients presented a tumoral response: the treatment is considered as not being effective enough,
=> The study will then be arrested in this 1st stage.
Time Frame
12 weeks after the 34th patient included
Secondary Outcome Measure Information:
Title
2nd step analysis : Safety and efficacy after 72patients included
Description
Only if 1st step is successful we can do the second step :
For toxicity : if >= 31patients show a decrease of their ADL (of 1.5 ADL or more) and/or
For efficacy : if <= 10 patients presented a tumoral response
=> Study is successful if :
we obtain at least 11 tumoral response and
maximum 30 patients on 72 evaluable are in loss of autonomy (ADL)
Time Frame
12 weeks after the 72th patient included
10. Eligibility
Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically proven ductal pancreatic carcinoma
Metastatic disease
First-line treatment : No previous chemotherapy in metastatic stage but adjuvant treatment before relapse (secondary metastatic) is permitted, provide it has been administered more than 6 months before)
Age of 70 yo or above
Normal DPD enzyme level or partial defect (excluding total defect)
Adequate bone marrow reserve: as indicated by : neutrophils >1500/mm3, platelets >100,000/ mm3, Hb >10.0g/dL.
Adequate Renal function as indicated by: MDRD creatinine clearance > 50ml/min.
Adequate hepatic function as indicated by: serum bilirubin < 1.5 times the upper limit of normal, AST and ALT < 2.5 times the upper limit of normal, or < 5 times the upper limit of normal if liver metastases are present.
Written informed consent must be obtained prior to protocol-specific procedures are being performed
Patient is affiliated to a social security category
Exclusion Criteria:
Other than ductal pancreatic carcinoma: namely endocrin tumors, acinar cells carcinoma, cystadenocarcinoma or adenocarcinoma of the ampulla of vater
Non-metastatic but locally advanced pancreatic adenocarcinoma
Complete DPD deficiency
History of Cardiac failure or symptomatic coronary artery disease
Autonomy Daily Living score by Katz <4
Prior treatment with FOLFIRINOX (adjuvant)
Major comorbidity likely to be an obstacle to treatment
Active or uncontrolled infection such as HIV or chronic B or C hepatitis
Uncontrolled diabetes mellitus
Prior peripheral neuropathy, grade > 2
Inflammatory bowel disease localized on the colon or rectum; bowel obstruction or severe uncontrolled diarrhea
Previous or concomitant malignancies other than effectively treated carcinoma in situ of the cervix or non-melanoma skin cancer
Hereditary fructose intolerance
Persons deprived of liberty or under guardianship
Any social, geographical or psychological condition which would compromise the ability to fully comply with the trial procedures and treatments
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandrine HIRET, MD
Organizational Affiliation
Institut de Cancérologie de l'Ouest (ICO) - Nantes, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
ICO Paul Papin
City
Angers
ZIP/Postal Code
49000
Country
France
Facility Name
CH Vendée
City
La Roche Sur Yon
ZIP/Postal Code
85925
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
ICM (Val d'Aurelle)
City
Montpellier Cedex 5
ZIP/Postal Code
34298
Country
France
Facility Name
Centre Eugène marquis
City
Rennes
ZIP/Postal Code
35042
Country
France
Facility Name
ICO René Gauducheau
City
Saint-Herblain
ZIP/Postal Code
44805
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy and Tolerance Evaluation in FOLFIRINOX Dose Adjusted in Elderly Patients With a Metastatic Pancreatic Cancer
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