Esophageal NeoplasmsPhase 2PROTECTNCT02359968
PReoperative Chemoradiation (Paclitaxel-carboplatin or FOLFOX) for Resectable Esophageal and Junctional Cancer
A Phase 2 study testing FOLFOX and CarboP-pacliT in people with Esophageal Neoplasms and Gastro-esophageal Junction Cancer, run by Centre Oscar Lambret at 10 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Neoplasms, Gastro-esophageal Junction Cancer
- What is being tested?
- FOLFOX and CarboP-pacliT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 10 sitesFrance
- Study dates
- 26 Feb 2015to 9 Feb 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 IIA (T3N0M0)
- stage IIB (T1 N1 M0 or T2 N1 M0),
- stage III (T3 N1 M0 or T4 N0 N1 M0) tumors
Show all 24Show fewer
- ECOG performance status 0, 1 or 2
- Patient eligible for preoperative chemoradiation with either fluorouracil- oxaliplatin-folinic acid, or Paclitaxel-carboplatin
- Age ≥ 18
- Peripheral neuropathy ≤ NCI-CTC grade 1
- 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
- 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 after randomization
- Negative pregnancy test (serum beta-HCG) performed within 1 week prior to start of study treatment in females with reproductive potential
- Patient covered by government health insurance
- Patient who provide a signed written informed consent form
Who cannot join
- Patient who present with stage I or stage IIA (including T2 N0 M0) 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
France10 sites
ICO Paul Papin
Angers
CHU Bordeaux
Bordeaux
University Hospital of Lille
Lille, 59000
Centre Oscar Lambret
Lille, 59020
Hôpital La Timone
Marseille
Hôpital Nord
Marseille
ICM - Val d'Aurelle
Montpellier
CH Lyon sud
Pierre-Bénite
Centre Eugène Marquis
Rennes
ICO René Gauducheau
Saint-Herblain
About this study
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
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.
Read the 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.
- Being tested
- FOLFOX, CarboP-pacliT
- Keywords
- resectable esophageal, junctional cancer, FOLFOX, paclitaxel-carboplatin
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFOXDrug
Also called Fluorouracil, Oxaliplatin, Folinic acid, Elvorine
radiochemotherapy before surgery
CarboP-pacliTDrug
Also called Carboplatine, paclitaxel
radiochemotherapy before surgery
| Study group | Role | What they receive |
|---|---|---|
| FOLFOX | Active comparator | * 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 Receives: Drug: FOLFOX |
| CarboP-pacliT | Experimental | * 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 Receives: Drug: CarboP-pacliT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Short-term benefit of 2 preoperative regimen: complete resection rate AND severe (grade ≥ 3) postoperative morbidity/mortality according to the Clavien-Dindo classification
Complete resection rate (R0, that is "complete removal of all tumor with microscopic examination of margins showing no tumor cells") AND severe (grade ≥ 3) postoperative morbidity/mortality according to the Clavien-Dindo classification. Severe postoperative complication is defined by grade ≥III per-operative or post-operative complication occurring in the 30 days after surgery.
Measured: up to 30 days after surgery
Secondary outcomes (7)
Rate of completion of full treatment without modification
Measured: up to 58 days
Evaluation of the efficacy of both regimen in term of overall survival
Overall survival using Kaplan-Meier method
Measured: From date of inclusion until the date of death from any cause assessed up to 36 months after the last surgery
Evaluation of the efficacy of both regimen in term of disease-free survival
Disease-free survival using Kaplan-Meier method
Measured: From date of inclusion until the date of first documented progression whichever came first, assessed up to 36 months after the last surgery
Evaluation of the safety of the evaluated regimens in terms of preoperative mortality.
Preoperative mortality (grade 5) rate, according to NCI-CTCAE v4.0 criteria
Measured: From registration to surgery
Evaluation of the safety of the evaluated regimens in terms of preoperative morbidities, postoperative morbidities, respiratory morbidities.
Pre-operative morbidities according to NCI-CTCAE v4.0 criteria, post-operative morbidities occurring in the 30 days after surgery with the main post-operative complication graded according to Clavien-Dindo, post-operative morbidities occurring more than 30 days after surgery graded according to NCI-CTCAE V4.0, postoperative respiratory morbidity rate according to the Clavien-Dindo classification.
Measured: From start of treatment to end of study
Evaluation of the efficacy of both regimen in term of Pathological response rate
Complete pathological response (ypCR) rate
Measured: Surgery
Evaluation of the efficacy of both regimen in term of quality of life
Quality of life: QLQC30 and OES18
Measured: Up to 3 years after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2015 (estimated)
- Study start26 Feb 2015
- Primary completion8 Jan 2021
- Study completion9 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Esophageal NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Oscar Lambret
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute, France
- Responsible party
- Sponsor
- Investigators
- Antoine ADENIS, MD, Principal investigator, Centre Oscar LambretGuillaume PIESSEN, MD, Principal investigator, University Hospital of Lille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02359968
- Sponsor's protocol ID
- PROTECT-1402
- Other IDs
- PHRC-K14-009, 2017-A03112-51
- Acronym
- PROTECT
- Status last verified
- Mar 2026
- First submitted
- 12 Jan 2015
- Last updated
- 18 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Messager M, Mirabel X, Tresch E, Paumier A, Vendrely V, Dahan L, Glehen O, Vasseur F, Lacornerie T, Piessen G, El Hajbi F, Robb WB, Clisant S, Kramar A, Mariette C, Adenis A. Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil-oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial. BMC Cancer. 2016 May 18;16:318. doi: 10.1186/s12885-016-2335-9.
PubMed 27194176
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02359968
- Acronym / sponsor ID
- PROTECT / PROTECT-1402
- Keywords
- resectable esophageal, junctional cancer, FOLFOX, paclitaxel-carboplatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Centre Oscar LambretUniversity, hospital or other
- Collaborators
- National Cancer Institute, France
- Study start
- 26 Feb 2015 (actual)
- Primary completion
- 8 Jan 2021 (actual)
- Study completion
- 9 Feb 2024 (actual)
- First posted
- 10 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FOLFOX | Active comparator | Drug: 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 |
| CarboP-pacliT | Experimental | Drug: 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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:
- ECOG performance status 0, 1 or 2
- Patient eligible for preoperative chemoradiation with either fluorouracil- oxaliplatin-folinic acid, or Paclitaxel-carboplatin
Key exclusion criteria (4 listed)
- Patient who present with stage I or stage IIA (including T2 N0 M0) 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FOLFOXAlso: Fluorouracil, Oxaliplatin, Folinic acid, Elvorineradiochemotherapy before surgery | Drug | FOLFOX |
| CarboP-pacliTAlso: Carboplatine, paclitaxelradiochemotherapy before surgery | Drug | CarboP-pacliT |
Primary outcome
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
Complete resection rate (R0, that is "complete removal of all tumor with microscopic examination of margins showing no tumor cells") AND severe (grade ≥ 3) postoperative morbidity/mortality according to the Clavien-Dindo classification. Severe postoperative complication is defined by grade ≥III per-operative or post-operative complication occurring in the 30 days after surgery.
7 secondary outcomes
Rate of completion of full treatment without modification
Time frame: up to 58 days
Evaluation of the efficacy of both regimen in term of overall survival
Time frame: From date of inclusion until the date of death from any cause assessed up to 36 months after the last surgery
Evaluation of the efficacy of both regimen in term of disease-free survival
Time frame: From date of inclusion until the date of first documented progression whichever came first, assessed up to 36 months after the last surgery
Evaluation of the safety of the evaluated regimens in terms of preoperative mortality.
Time frame: From registration to surgery
Evaluation of the safety of the evaluated regimens in terms of preoperative morbidities, postoperative morbidities, respiratory morbidities.
Time frame: From start of treatment to end of study
Evaluation of the efficacy of both regimen in term of Pathological response rate
Time frame: Surgery
Evaluation of the efficacy of both regimen in term of quality of life
Time frame: Up to 3 years after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2026.
- Derived from this study: PubMed 27194176Messager M, Mirabel X, Tresch E, Paumier A, Vendrely V, Dahan L, Glehen O, Vasseur F, Lacornerie T, Piessen G, El Hajbi F, Robb WB, Clisant S, Kramar A, Mariette C, Adenis A. Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil-oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial. BMC Cancer. 2016 May 18;16:318. doi: 10.1186/s12885-016-2335-9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antoine ADENIS, MD principal investigator
Centre Oscar Lambret
Guillaume PIESSEN, MD principal investigator
University Hospital of Lille
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FOLFOX and CarboP-pacliT in people with Esophageal Neoplasms and Gastro-esophageal Junction Cancer, run by Centre Oscar Lambret at 10 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02359968, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2026.