Efficacy and Tolerance Evaluation in FOLFIRINOX Dose Adjusted in Elderly Patients With a Metastatic Pancreatic Cancer (PAMELA70)
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|ClinicalTrials.gov Identifier: NCT02143219|
Recruitment Status : Active, not recruiting
First Posted : May 21, 2014
Last Update Posted : March 24, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Pancreatic Metastatic Cancer Toxicity||Drug: Oxaliplatine Drug: Folinic acid Drug: Irinotecan Drug: 5-FU||Phase 2|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||72 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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.|
|Actual Study Start Date :||July 31, 2014|
|Estimated Primary Completion Date :||July 31, 2020|
|Estimated Study Completion Date :||July 31, 2022|
FOLFIRINOX (D1-D15, for maximum 12 cycles) = Oxaliplatine + Folinic acid + Irinotecan + 5-FU
Oxaliplatine : 85mg/m², 2-hours IV infusion (D1), then,
Other Name: Eloxatine®
Drug: Folinic acid
Folinic acid (FA): 400 mg/m² , 2-hour IV infusion (D1),
Irinotecan (at the dosage determined by the UGT1A1 status), 90 min IV infusion starting 30 min after the FA starts
Other Name: Campto®
5-FU (according to the DPD pharmacogenetic status), continuous IV infusion of 46 hours, starting at the end of FA infusion:
Other Name: 5-fluorouracile
- 1st step analysis : Safety and efficacy after 34 patients included [ Time Frame: 12 weeks after the 34th patient 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.
- 2nd step analysis : Safety and efficacy after 72patients included [ Time Frame: 12 weeks after the 72th patient 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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02143219
|ICO Paul Papin|
|Angers, France, 49000|
|La Roche Sur Yon, France, 85925|
|Centre Oscar Lambret|
|Lille, France, 59020|
|ICM (Val d'Aurelle)|
|Montpellier Cedex 5, France, 34298|
|Centre Eugène marquis|
|Rennes, France, 35042|
|ICO René Gauducheau|
|Saint-Herblain, France, 44805|
|Principal Investigator:||Sandrine HIRET, MD||Institut de Cancérologie de l'Ouest (ICO) - Nantes, France|