Toxicity Clinical Trial
— PAMELA70Official 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.
Verified date | July 2022 |
Source | Institut Cancerologie de l'Ouest |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 72 |
Est. completion date | November 25, 2020 |
Est. primary completion date | November 25, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 70 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
France | ICO Paul Papin | Angers | |
France | CH Vendée | La Roche Sur Yon | |
France | Centre Oscar Lambret | Lille | |
France | ICM (Val d'Aurelle) | Montpellier Cedex 5 | |
France | Centre Eugène marquis | Rennes | |
France | ICO René Gauducheau | Saint-Herblain |
Lead Sponsor | Collaborator |
---|---|
Institut Cancerologie de l'Ouest |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. |
12 weeks after the 34th patient included | |
Secondary | 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) |
12 weeks after the 72th patient included |
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