Clinical trial NCT01964534: Efficacy of ABI-007 Plus Gemcitabine or sLV5FU2 as First-line Therapy in Patients With Metastatic Pancreatic Cancer
Official title: Randomized Phase II Study of Weekly ABI-007 Plus Gemcitabine or Simplified LV5FU2 as First-line Therapy in Patients With Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Pancreatic Cancer
Keywords: Metastatic
Pancreatic
Cancer
Pancreas
GERCOR
Gemcitabine
LV5FU2
ABI-007
PACLITAXEL ALBUMIN-BOUND PARTICLES
Lead sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2013-10-17
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the combination of ABI-007 with gemcitabine or with LV5FU2.

Detailed description: Gemcitabine alone or the triplet combination of 5FU, irinotecan and oxaliplatin (FOLFIRINOX)are the reference 1st line treatment for metastatic pancreatic cancer.

The aim of the AFUGEM study is to evaluate the efficacy of weekly ABI-007 in combination with weekly gemcitabine or with fortnightly simplified LV5FU2 regimen in terms of progression-free survival in patients with previously untreated metastatic pancreatic cancer.

ABI-007 has been approved for commercialization in 38 countries, including the US, Canada, the EU, Australia, China, India and Korea for the treatment of women with metastatic breast cancer. ABI-007 alone and in combination is being evaluated in a number of cancers, including metastatic melanoma, non-small cell lung cancer, pancreatic cancer, and other solid tumors. Conditions which are responsive to paclitaxel such as non-hematological solid tumor malignancies are good clinical candidates for treatment with ABI-007.

Eligibility criteria: Inclusion Criteria:

1. Signed and dated informed consent, and willing and able to comply with protocol requirements,
2. Histologically or cytologically proven adenocarcinoma of the pancreas,
3. Metastatic disease confirmed (stage IV),
4. No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be \>12 months),
5. At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1 guidelines,
6. Age ≥18 years,
7. ECOG Performance status (PS) 0-2,
8. Hematological status: neutrophils (ANC) \>1.5x109/L; platelets \>100x109/L; haemoglobin ≥9g/dL,
9. Adequate renal function: serum creatinine level \<150µM,
10. Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (≤5xULN in case of liver metastases)
11. Total bilirubin ≤1.5 x ULN, albumin ≥25g/L
12. Baseline evaluations performed before randomization: clinical and blood evaluations no more than 2 weeks (14 days) prior to randomization, tumor assessment (CT-scan or MRI, evaluation of non-measurable lesions) no more than 3 weeks (21 days) prior to randomization,
13. Female patients must be surgically sterile, or be postmenopausal, or must commit to using reliable and appropriate methods of contraception during the study and during at least six months after the end of study treatment (when applicable). All female patients with reproductive potential must have a negative pregnancy test (β HCG) within 72 hours prior to starting ABI-007 treatment. Breastfeeding is not allowed. Male patients must agree to use effective contraception in addition to having their partner use a contraceptive method as well during the trial and during at least six months after the end of the study treatment,
14. Registration in a national health care system (CMU included for France).

Exclusion Criteria:

1. History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy)
2. Local or locally advanced disease (stage I to III),
3. Patient uses warfarin,
4. Uncontrolled hypercalcemia,
5. Pre-existing permanent neuropathy (NCI grade ≥2),
6. Known dihydropyrimidine dehydrogenase (DPD) deficiency,
7. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
8. Treatment with any other investigational medicinal product within 28 days prior to study entry,
9. Other serious and uncontrolled non-malignant disease (eg. active infection requiring systemic therapy, coronary stenting or myocardial infarction or stroke in the past 6 months),
10. Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C.
11. History or active interstitial lung disease (ILD),
12. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for \>5 years,
13. Patients with known allergy to any excipient of study drugs,
14. Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine and concomitant administration of prophylactic phenytoin

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: time interval from randomization to the date of first documented disease progression or death from any cause, whichever occurs first.Assessed at 4 months.
Secondary outcomes:
measure: Tumor Response Rate
timeFrame: Assessed every 2 months during treatment period (- Estimated treatment duration per patient : 6 months).
measure: Duration of disease control (DDC)
timeFrame: Assessed up to 30 months after the beginning of the study
measure: Overall Survival
timeFrame: time interval from inclusion to the date of death from any cause. Assessed up to 30 months after the beginning of the study.
measure: Quality of life
timeFrame: Assessed from study entry to 1 month after last study drug administration and up to 30 months after the beginning of the study.
measure: Number of Adverse Events
timeFrame: Assessed from study entry to 1 month after last study drug administration, assessed up to 30 months after the beginning of the study
Other outcomes:
Locations:
city: Angers
country: France
facility: Institut de cancérologie de l'Ouest - Paul Papin
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Clichy
country: France
facility: Hôpital Beaujon
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: CHU la Timone
city: Mont de Marsan
country: France
facility: Centre Hospitalier Layné
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Reims
country: France
facility: CHU de Reims Hôpital Robert Debré
city: Saint Herblain
country: France
facility: Institut de Cancérologie de l'Ouest - Réné Gauducheau
city: Tours
country: France
facility: Hôpital Trousseau - CHRU Tours
Study officials:
affiliation: Hôpital La Pitié-Salpêtrière
name: Jean-Baptiste Bachet, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bachet JB, Hammel P, Desrame J, Meurisse A, Chibaudel B, Andre T, Debourdeau P, Dauba J, Lecomte T, Seitz JF, Tournigand C, Aparicio T, Meyer VG, Taieb J, Volet J, Monier A, Bonnetain F, Louvet C. Nab-paclitaxel plus either gemcitabine or simplified leucovorin and fluorouracil as first-line therapy for metastatic pancreatic adenocarcinoma (AFUGEM GERCOR): a non-comparative, multicentre, open-label, randomised phase 2 trial. Lancet Gastroenterol Hepatol. 2017 May;2(5):337-346. doi: 10.1016/S2468-1253(17)30046-8. Epub 2017 Feb 28.
citation: Bachet JB, Chibaudel B, Bonnetain F, Validire P, Hammel P, Andre T, Louvet C; GERCOR group. A randomized phase II study of weekly nab-paclitaxel plus gemcitabine or simplified LV5FU2 as first-line therapy in patients with metastatic pancreatic cancer: the AFUGEM GERCOR trial. BMC Cancer. 2015 Oct 6;15:653. doi: 10.1186/s12885-015-1656-4.