PET Imaging-guided Chemoradiotherapy in Esophageal Squamous Cell Carcinoma

Sponsor

Mian XI (Other)

Overall Status

Recruiting

CT.gov ID

NCT03791905

Collaborator

(none)

216

Enrollment

Location

Arms

58.5

Anticipated Duration (Months)

3.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Neoplasm, Esophageal Squamous Cell Carcinoma	Drug: Paclitaxel Drug: Cisplatin Drug: Oxaliplatin Drug: 5-FU Drug: Leucovorin Radiation: Intensity-modulated radiotherapy Device: PET	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

216 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized parallel studyRandomized parallel study

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 15, 2019

Anticipated Primary Completion Date :

Jul 1, 2021

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TP Arm 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 chemotherapy drug Other Names: Taxol Drug: Cisplatin chemotherapy drug Other Names: DDP Radiation: Intensity-modulated radiotherapy radiotherapy technique Other Names: IMRT Device: PET Using PET to evaluate response to induction chemotherapy Other Names: PET-CT
Experimental: FOLFOX Arm 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 chemotherapy drug Other Names: OXA Drug: 5-FU chemotherapy drug Other Names: Fluorouracil Drug: Leucovorin chemotherapy drug Other Names: CF Radiation: Intensity-modulated radiotherapy radiotherapy technique Other Names: IMRT Device: PET Using PET to evaluate response to induction chemotherapy Other Names: PET-CT

Arm

Intervention/Treatment

Experimental: TP Arm

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

chemotherapy drug

Other Names:

Taxol

Drug: Cisplatin

chemotherapy drug

Other Names:

DDP

Radiation: Intensity-modulated radiotherapy

radiotherapy technique

Other Names:

IMRT

Device: PET

Using PET to evaluate response to induction chemotherapy

Other Names:

PET-CT

Experimental: FOLFOX Arm

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

chemotherapy drug

Other Names:

OXA

Drug: 5-FU

chemotherapy drug

Other Names:

Fluorouracil

Drug: Leucovorin

chemotherapy drug

Other Names:

Radiation: Intensity-modulated radiotherapy

radiotherapy technique

Other Names:

IMRT

Device: PET

Using PET to evaluate response to induction chemotherapy

Other Names:

PET-CT

Outcome Measures

Primary Outcome Measures

clinical complete response [3 months after the treatment (plus or minus 7 days)]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.