Clinical Trials /

NAB-PACLITAXEL Plus FOLFOX as Perioperative Chemotherapy in Patients With Operable Oesogastric Adenocarcinoma

NCT02486601

Description:

This is a non-randomized pauci-centre, open-label phase II study. The treatment will consist in a chemotherapy by FOLFOX and nab-paclitaxel following modalities determined in the Brown University Phase I study. In neoadjuvant setting : 3 months of treatment Main criteria of Withdraw of the treatment: in case of tumor progression, non acceptable toxicity, or patient decision. Post-operative treatment (for 6 additional cycles) is recommended, but will depend on the result of the neo-adjuvant treatment and the ability of patients to receive adjuvant chemotherapy based on tolerance of neo-adjuvant treatment and general post-operative condition (i.e. adjuvant treatment if no progression during neo-adjuvant chemotherapy, less than 80% of residual viable tumor compared to initial tumor volume, acceptable tolerance and post-operative PS 0 - 2). Adjuvant treatment must be initiated within 8 weeks post-operatively.

Related Conditions:
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: NAB-PACLITAXEL Plus FOLFOX as Perioperative Chemotherapy in Patients With Operable Oesogastric Adenocarcinoma
  • Official Title: Phase II Study of NAB-PACLITAXEL Plus FOLFOX as Perioperative Chemotherapy in Patients With Operable Oesogastric Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: FOXAGAST -D14-1
  • NCT ID: NCT02486601

Conditions

  • Cancer of Stomach

Interventions

DrugSynonymsArms
nab-paclitaxelABRAXANEnab-paclitaxel + FOLFOX
FOLFOXnab-paclitaxel + FOLFOX

Purpose

This is a non-randomized pauci-centre, open-label phase II study. The treatment will consist in a chemotherapy by FOLFOX and nab-paclitaxel following modalities determined in the Brown University Phase I study. In neoadjuvant setting : 3 months of treatment Main criteria of Withdraw of the treatment: in case of tumor progression, non acceptable toxicity, or patient decision. Post-operative treatment (for 6 additional cycles) is recommended, but will depend on the result of the neo-adjuvant treatment and the ability of patients to receive adjuvant chemotherapy based on tolerance of neo-adjuvant treatment and general post-operative condition (i.e. adjuvant treatment if no progression during neo-adjuvant chemotherapy, less than 80% of residual viable tumor compared to initial tumor volume, acceptable tolerance and post-operative PS 0 - 2). Adjuvant treatment must be initiated within 8 weeks post-operatively.

Detailed Description

      This is a non-randomized pauci-centre, open-label phase II study. The treatment will consist
      in a chemotherapy by FOLFOX and nab-paclitaxel following modalities determined in the Brown
      University Phase I study.

      In neoadjuvant setting : 3 months of treatment

      Main criteria of Withdraw of the treatment: in case of tumor progression, non acceptable
      toxicity, or patient decision.
    

Trial Arms

NameTypeDescriptionInterventions
nab-paclitaxel + FOLFOXExperimentalnab-paclitaxel + FOLFOX nab-paclitaxel: 150 mg/m2 D1 every 2 weeks Leucovorin: 400 mg/m2 D1 every 2 weeks Oxaliplatin: 85 mg/m2 D1 every 2 weeks 5-FU infusion: 2400mg/m2 48h infusion every 2 weeks 6 pre-operative cycles 6 post-operative cycles (optional)
  • nab-paclitaxel
  • FOLFOX

Eligibility Criteria

        Inclusion Criteria:

          -  Signed and dated informed consent, and willing and able to comply with protocol
             requirements,

          -  Histologically or cytologically proven adenocarcinoma of the low oesophagus or of the
             stomach, (from 1/3 inferior of the oesophagus to pylorus)

          -  HER2 negative tumors

          -  Localized and operable disease confirmed (stage I-III),

          -  No prior therapy for localized disease ,

          -  Age ≥18 years,

          -  Performance status (PS) 0-2,

          -  Haematological status: neutrophils (ANC) > 2.0x109/L; platelets >100x109/L;
             haemoglobin ≥9g/dL,

          -  Adequate renal function: serum creatinine level <150µM and creatinine clearance test >
             30mL/min,

          -  Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (Upper Limit of Normal)

          -  Total bilirubin ≤1.5 x ULN,

          -  Albumin ≥25g/L

          -  Baseline evaluations performed before inclusion: clinical and blood evaluations no
             more than 2 weeks (14 days) prior to inclusion, tumor assessment (CT-scan, evaluation
             of non-measurable lesions) no more than 3 weeks (21 days) prior to inclusion,

          -  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 days prior to starting nab-paclitaxel neo-adjuvant and adjuvant
             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,

          -  Registration in a national health care system (CMU included for France).

        Exclusion Criteria:

          -  Metastatic disease (stage IV)

          -  Non operable primary tumor

          -  Patient using warfarin,

          -  Uncontrolled hypercalcemia (corrected serum calcium > 2.55 mmol/l),

          -  Pre-existing permanent neuropathy (NCI grade ≥2),

          -  Known dihydropyrimidine dehydrogenase (DPD) deficiency,

          -  Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted
             therapy, immunotherapy),

          -  Treatment with any other investigational medicinal product within 28 days prior to
             study entry,

          -  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),

          -  Known or historical active infection with HIV, or known active infection untreated
             with hepatitis B or hepatitis C.

          -  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,

          -  Patients with known allergy to any excipient of study drugs,

          -  Concomitant administration of live, attenuated virus vaccine such as yellow fever
             vaccine and concomitant administration of prophylactic phenytoin

          -  Patient with any medical or psychological condition, deemed by the investigator to
             likely interfere with patient's ability to sign informed consent or cooperate and
             participate in the study, including tutelage or guardianship.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete pathological response rate
Time Frame:after three months of neoadjuvant chemotherapy
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease Free Survival (DFS)
Time Frame:time from the date of inclusion up to the date of disease progression or death whichever occurs last up to 7 years
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:time interval form the inclusion to the date of the death from any cause up to 7 years
Safety Issue:
Description:
Measure:Health related to Quality of Life (QoL)
Time Frame:up to 8 months
Safety Issue:
Description:
Measure:Safety profile of the combination of nab-paclitaxel + FOLFOX regimen assessed by adverse events
Time Frame:time from randomisation up to end of study up to 7 years
Safety Issue:
Description:
Measure:Assessment of biomarkers when appropriate
Time Frame:1 day of biopsie from diagnosis, and tumor from surgery
Safety Issue:
Description:such as SPARC, TS, DPD, ERCC1
Measure:Assessment of genetic polymorphism involved in tumor-response when appropriate
Time Frame:28 days after last study treatment
Safety Issue:
Description:CYP2A6, TS, DPD, ERCC1, ERCC2

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:GERCOR - Multidisciplinary Oncology Cooperative Group

Last Updated

December 18, 2017