PET Imaging-guided Chemoradiotherapy in Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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Since multiple studies have demonstrated that PET can identify responders and non-responders to induction chemotherapy, using FDG-PET imaging to guide treatment decisions has prompted interest in clinical practice. The aim of this study was to evaluate whether changing chemotherapy regimen during radiation based on PET response to induction chemotherapy can improve clinical complete response (cCR) in patients with unresectable esophageal squamous cell carcinoma (ESCC).

Detailed Description
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A total of 216 patients with baseline PET scan were randomized to one of 2 induction chemotherapy arms: paclitaxel/cisplatin (TP) on days 1, 22 or FOLFOX (oxaliplatin, leucovorin, 5-FU) on days 1, 15, 29. Repeat PET was performed on days 36-42 and changes in max standardized uptake value (SUVmax) from baseline were assessed. Using a predefined cut-off value of a 35% decrease in SUVmax, PET responders (≥35% decrease in SUVmax) continued on the same chemotherapy regimen during radiotherapy, whereas PET non-responders (<35% decrease in SUVmax) crossed over to an alternative chemotherapy regimen concomitantly with radiation. All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is generally 50-60 Gy in 25-28 fractions, 5 days per week.

Official Title
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A Phase II Randomized Trial of PET Imaging in Assessing Response to Induction Chemotherapy in Esophageal Squamous Cell Carcinoma Treated With Definitive Chemoradiotherapy

Conditions
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Neoplasm, Esophageal, Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Cisplatin
* Drug: Oxaliplatin
* Drug: 5-FU
* Drug: Leucovorin
* Radiation: Intensity-modulated radiotherapy
* Device: PET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed squamous cell carcinoma of the esophagus; Absence of hematogenous metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan (according to UICC TNM version 8); Not suitable for surgery (either for medical reasons or patient's choice); Age at diagnosis 18 to 70 years; Eastern Cooperative Oncology Group performance status ≤ 2 No prior cancer therapy; No history of concomitant or previous malignancy; Hematologic function: WBC ≥ 4.0×109/L, PLT ≥ 80×109/L, Hb ≥ 10mg/dL; Renal function: Cr ≤ 1.25×UNL; Hepatic function: BIL ≤ 1.5×UNL, ALT/AST ≤ 2.5×UNL; Documented informed consent to participate in the trial. Exclusion Criteria: Younger than 18 or older than 70 years of age; ECOG performance status of 3 or above; Other cancer history; Previous radiotherapy history; Subjects with distant metastases; Pregnancy or breast feeding. Women of childbearing age must use effective contraception; Serious cardiovascular disease (congestive heart failure, uncontrollable arrhythmia, unstable angina, myocardial infarction, serious heart valve disease, resistant hypertension); Evidence of bleeding diathesis or serious infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized parallel study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TP Arm<br>Patients with baseline PET scan assigned to this Arm will receive two cycles of 3-weekly schedule of induction chemotherapy with paclitaxel/cisplatin (TP), consisting of paclitaxel 150 mg/m2 on day 1 and cisplatin 75 mg/m2 on day 1. Repeat PET was performed on days 36-42 and changes in SUVmax from baseline were assessed. PET responders (≥35% decrease in SUVmax) continued on the same chemotherapy regimen during radiotherapy, whereas PET non-responders (<35% decrease in SUVmax) crossed over to FOLFOX regimen concomitantly with radiation. All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is generally 50-60 Gy in 25-28 fractions. | Drug: Paclitaxel<br>* chemotherapy drug<br>* Other names: Taxol;Drug: Cisplatin<br>* chemotherapy drug<br>* Other names: DDP;Radiation: Intensity-modulated radiotherapy<br>* radiotherapy technique<br>* Other names: IMRT;Device: PET<br>* Using PET to evaluate response to induction chemotherapy<br>* Other names: PET-CT;|
| Experimental: FOLFOX Arm<br>Patients with baseline PET scan assigned to this Arm will receive three cycles of 2-weekly schedule of induction chemotherapy with FOLFOX (oxaliplatin, leucovorin, 5-FU), consisting of oxaliplatin 85 mg/m2 on day 1, leucovorin 400 mg/m2, and 5-FU 2 g/m2 on day 1. Repeat PET was performed on days 36-42 and changes in SUVmax from baseline were assessed. PET responders (≥35% decrease in SUVmax) continued on the same chemotherapy regimen during radiotherapy, whereas PET non-responders (<35% decrease in SUVmax) crossed over to TP regimen concomitantly with radiation. All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is generally 50-60 Gy in 25-28 fractions. | Drug: Oxaliplatin<br>* chemotherapy drug<br>* Other names: OXA;Drug: 5-FU<br>* chemotherapy drug<br>* Other names: Fluorouracil;Drug: Leucovorin<br>* chemotherapy drug<br>* Other names: CF;Radiation: Intensity-modulated radiotherapy<br>* radiotherapy technique<br>* Other names: IMRT;Device: PET<br>* Using PET to evaluate response to induction chemotherapy<br>* Other names: PET-CT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical complete response | RECIST (Response Evaluation Criteria in Solid Tumors) criteria was used to determine the tumor response. Tumor response was evaluated 3 months after the completion of treatment based on CT or PET-CT scans, endoscopy with biopsies. | 3 months after the treatment (plus or minus 7 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From the enrollment to the date of death from any cause or date of lost follow-up | 3 years after randomization | 
| Progression-free survival | From the date of randomization to the date of disease progression or last follow-up | 3 years after randomization | 
| Chemoradiotherapy-related toxicity | Treatment-related toxicity | From the date of randomization to the 3 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophageal squamous cell carcinoma, PET, Definitive chemoradiotherapy, Induction chemotherapy