PReoperative Chemoradiation (Paclitaxel-carboplatin or FOLFOX) for Resectable Esophageal and Junctional Cancer (PROTECT)
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| ClinicalTrials.gov Identifier: NCT02359968 |
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Recruitment Status :
Active, not recruiting
First Posted : February 10, 2015
Last Update Posted : October 27, 2021
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Esophageal Neoplasms | Drug: FOLFOX Drug: CarboP-pacliT | Phase 2 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 106 participants |
| Allocation: | Randomized |
| Intervention Model: | Factorial Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | February 26, 2015 |
| Estimated Primary Completion Date : | June 2022 |
| Estimated Study Completion Date : | June 2023 |
| Arm | Intervention/treatment |
|---|---|
Active Comparator: FOLFOX
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Drug: FOLFOX
radiochemotherapy before surgery
Other Names:
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Experimental: CarboP-pacliT
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Drug: CarboP-pacliT
radiochemotherapy before surgery
Other Names:
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- 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 ]
- Rate of completion of full treatment without modification [ Time Frame: up to 58 days ]
- Recurrence rate [ Time Frame: From date of inclusion until the date of first documented progression whichever came first, assessed up to 5 years ]
- disease-free survival [ Time Frame: From date of inclusion until the date of death from any cause assessed up to 5 years ]
- Tolerance according to NCI-CTCAE v4.0 and Clavien-Dindo [ Time Frame: up to 30 days after surgery ]
- DVH (CoDose-Volume-Histogram (DVH) and postoperative respiratory morbidity [ Time Frame: up to 30 days after the beginning of radiotherapy ]
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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)
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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)
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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:
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02359968
| France | |
| University Hospital of Lille | |
| Lille, France, 59000 | |
| Centre Oscar Lambret | |
| Lille, France, 59020 | |
| Principal Investigator: | Antoine ADENIS, MD | Centre Oscar Lambret | |
| Principal Investigator: | Christophe MARIETTE, MD | University Hospital of Lille |
| Responsible Party: | Centre Oscar Lambret |
| ClinicalTrials.gov Identifier: | NCT02359968 |
| Other Study ID Numbers: |
PROTECT-1402 |
| First Posted: | February 10, 2015 Key Record Dates |
| Last Update Posted: | October 27, 2021 |
| Last Verified: | October 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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resectable esophageal junctional cancer FOLFOX paclitaxel-carboplatin |
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Esophageal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Head and Neck Neoplasms Digestive System Diseases Esophageal Diseases Gastrointestinal Diseases Paclitaxel Fluorouracil Oxaliplatin |
Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites Antimetabolites, Antineoplastic Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |