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History of Changes for Study: NCT02359968
PReoperative Chemoradiation (Paclitaxel-carboplatin or FOLFOX) for Resectable Esophageal and Junctional Cancer (PROTECT)
Latest version (submitted October 19, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 February 9, 2015 None (earliest Version on record)
2 May 14, 2019 Study Status and IPDSharing
3 October 19, 2021 Recruitment Status, Study Status, Contacts/Locations and Study Design
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Study NCT02359968
Submitted Date:  February 9, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: PROTECT-1402
Brief Title: PReoperative Chemoradiation (Paclitaxel-carboplatin or FOLFOX) for Resectable Esophageal and Junctional Cancer (PROTECT)
Official Title: PReoperative Chemoradiation With Paclitaxel-carboplatin or With Fluorouracil-oxaliplatine-acide Folinique (FOLFOX) for Resectable Esophageal and Junctional Cancer - A Randomized Phase II Trial
Secondary IDs:
Open or close this module Study Status
Record Verification: February 2015
Overall Status: Recruiting
Study Start: January 2015
Primary Completion: April 2018 [Anticipated]
Study Completion: October 2018 [Anticipated]
First Submitted: January 12, 2015
First Submitted that
Met QC Criteria:
February 9, 2015
First Posted: February 10, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
February 9, 2015
Last Update Posted: February 10, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Centre Oscar Lambret
Responsible Party: Sponsor
Collaborators: National Cancer Institute, France
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary:

Resectable esophageal or junctional cancer requires medical treatment by radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy treatment is the FOLFOX. It is a combination of three drugs administered intravenously: fluorouracil, oxaliplatin and folinic acid. This is the standard treatment.

Another protocol of chemotherapy is widely used by certain European and American teams, due to promising results : a combination of two drugs administered intravenously: Paclitaxel and Carboplatin (CarboP-pacliT). At present, no clinical study has shown the superiority of one treatment over the other.

The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments.

Detailed Description:

There is no standard preoperative (neoadjuvant) chemoradiation (NCRT) regimen for resectable esophageal cancer, because most if all trials failed to show any survival advantage favoring pCRT when compared to surgery only. This failure had been related to the lack of power of some trials, as well as the ability of chemoradiation to potentiate post-operative morbidity (including mortality), and therefore hampering the accrual of its own survival benefit. Hopefully, meta-analyses showed that NCRT increases survival when compared to surgery only. However, in the clinical practice, this does not make easier the choice of the best NCRT treatment. It appeared that the radiation regimen that were used in each randomized trials were heterogeneous with respect with dose, fraction, length of treatment, fields, dosimetry planning, and quality control. This applies also to chemotherapy with respect with the kind of cytotoxics that were used (including number of drugs), as well as dosage, and the number of cycles, although most of the time cytotoxics were fluorouracil and cisplatin.

Dutch colleagues recently showed that NCRT with weekly carboplatin and paclitaxel increase survival, without increasing postoperative mortality. Of note, most tumors in this trial arose from the lower third of the esophagus and esogastric junction and these habitually correlate with less postoperative morbidity compared to upper third tumors. Moreover, the lung volume spared from radiation was greater in junctional tumors than in upper third cancers - a critical point in the development of radiation-induced pneumonitis and subsequent postoperative mortality. It is difficult to understand how this taxane-based chemotherapy is active, as it did not make better that fluorouracil-based regimen in non-operable patients, and as NCRT with taxanes makes radiation-induced pneumonitis more likely. The favorable impact of this NCRT may lie on its radiation regimen. A moderate total dose of radiation, smaller radial margins than in other trials and modern dosimetry with 3D-planning all improve the safety of treatment and of subsequent surgery. Finally, the favorable impact of the Dutch NCRT regimen may lies on the fact that it does not include cisplatin, a compound which has been found related to the occurrence of more sudden deaths than a non cisplatin-based regimen such as the FOLFOX combination (fluorouracil, oxaliplatin, folinic acid) in the setting of definitive chemoradiotherapy.

Our aim is to evaluate the short-term benefit (complete resection rate) and safety (severe postoperative rate) of 2 preoperative regimen, (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid), combined to the Dutch radiation backbone, in operable esophageal and junctional (Siewert I-II) cancer. The present trial offers the unique opportunity to compare two therapeutic strategies that have already been shown to be efficient in large randomized controlled trials offering level-1 evidence.

Open or close this module Conditions
Conditions: Esophageal Neoplasms
Keywords: resectable esophageal
junctional cancer
FOLFOX
paclitaxel-carboplatin
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Factorial Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 106 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: FOLFOX
  • Fluorouracil 400 mg/m², IV bolus dose on day 1, followed by continuous IV infusion of fluorouracil 1600 mg/m² over 2 days
  • Oxaliplatin 85 mg/m², 2-hr IV infusion on day 1
  • Folinic acid 200 mg/m² 2-hr IV infusion on day 1
  • 3 cycles, q14
Drug: FOLFOX
radiochemotherapy before surgery
Other Names:
  • Fluorouracil
  • Oxaliplatin
  • Folinic acid
  • Elvorine
Experimental: CarboP-pacliT
  • Carboplatin (carboP) AUC=2, given by intravenous infusion
  • Paclitaxel (pacliT) 50 mg/m², given by intravenous infusion
  • on days 1, 8, 15, 22 and 29
Drug: CarboP-pacliT
radiochemotherapy before surgery
Other Names:
  • Carboplatine
  • paclitaxel
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Short-term benefit of 2 preoperative regimen: complete resection rate AND severe (grade ≥ 3) postoperative morbidity/mortality according to the Clavien-Dindo classification
[ Time Frame: up to 30 days after surgery ]

Secondary Outcome Measures:
1. Rate of completion of full treatment without modification
[ Time Frame: up to 58 days ]

2. Recurrence rate
[ Time Frame: From date of inclusion until the date of first documented progression whichever came first, assessed up to 5 years ]

3. disease-free survival
[ Time Frame: From date of inclusion until the date of death from any cause assessed up to 5 years ]

4. Tolerance according to NCI-CTCAE v4.0 and Clavien-Dindo
[ Time Frame: up to 30 days after surgery ]

Other Outcome Measures:
1. DVH (CoDose-Volume-Histogram (DVH) and postoperative respiratory morbidity
[ Time Frame: up to 30 days after the beginning of radiotherapy ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 75 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Resectable and operable esophageal cancer located under the carena (beyond 25 cm from the incisors) or junctional cancer (Siewert I or II)
  • Invasive adenocarcinoma or squamous cell type (to stick to the population included in the CROSS trial)
  • Patient who present with:
    • stage IIB (T1 N1 M0 or T2 N1 M0),
    • stage III (T3 N1 M0 or T4 N0 N1 M0) tumors (appendix 5)
  • ECOG performance status 0, 1 or 2 (appendix 7)
  • Patient eligible for preoperative chemoradiation with either fluorouracil- oxaliplatin-folinic acid, or Paclitaxel-carboplatin
  • Age ≥ 18 and ≤ 75 years
  • Peripheral neuropathy ≤ NCI-CTC grade 1 (appendix 3)
  • Adequate bone marrow reserve, normal renal and liver functions:
    • Neutrophil count ≥ 1500/mm3
    • Platelet count ≥ 100 000/mm3
    • Hemoglobin ≥ 10 g/dl (after transfusion, if necessary)
    • Creatinin < 15mg/L
    • Clearance of creatinin (Cockcroft formulae) ≥ 60 ml/mn (appendix 6)
    • Prothrombin time ≥ 60%
    • ASAT-ALAT ≤2.5 x ULN
    • Total bilirubin < 1.5 x ULN
    • Albumin greater the lower limit of normal
  • Start of treatment within 28 days of inclusion
  • Negative pregnancy test (serum beta-HCG) performed within 1 week prior to start of study treatment in females with reproductive potential

Exclusion Criteria:

  • Patient who present with stage I or stage IIA (including T3 N0) or stage IV
  • Patient who present with common contraindications for surgery related to patient status
  • Patient who present with common contraindications for surgery related to disease extension
  • Patient who present with common contraindication to radiochemotherapy with either fluorouracile-cisplatin or with paclitaxel-carboplatin:
Open or close this module Contacts/Locations
Central Contact Person: Antoine ADENIS, MD
Telephone: +33 3 20 29 59 18
Email: a-adenis@o-lambret.fr
Study Officials: Antoine ADENIS, MD
Principal Investigator
Centre Oscar Lambret
Christophe MARIETTE, MD
Principal Investigator
University Hospital of Lille
Locations: France
University Hospital of Lille
[Recruiting]
Lille, France, 59000
Centre Oscar Lambret
[Recruiting]
Lille, France, 59020
Contact:Contact: Antoine ADENIS, MD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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