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Stage III Esophageal Squamous Cell CarcinomaPhase 2NCT02812641

Neoadjuvant CCRT With/Without Bevacizumab for Locally Advanced ESCC

A Phase 2 study testing BPF-CCRT (run-in), BPF-CCRT (randomized) and PF-CCRT (randomized) in people with Stage III Esophageal Squamous Cell Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Esophageal squamous cell carcinoma (ESCC) is one of the ten leading cancers in Taiwanese male. The prognosis is poor with a five-year overall survival rate of 10 to 30 %. Randomized clinical trials have demonstrated that trimodality therapy (TMT), consisted of neoadjuvant concurrent chemoradiation (CCRT) and radical… Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
BPF-CCRT (run-in), BPF-CCRT (randomized) and PF-CCRT (randomized)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteTaiwan
Study dates
Jun 2016to Dec 2021
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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • To be eligible for inclusion, patients must fulfill the following criteria:
  • Histologically proved squamous cell carcinoma of esophagus
  • Locoregional advanced stage III disease, which are defined by Tumor, Nodes, Metastases (TNM) system of American Joint Committee on Cancer (AJCC) Cancer Staging System (7th edition) in 2010, fulfilling one of the following criteria:
  • T1-2 N2-3 M0
  • T3 N1-3 M0
  • Medical fit for curative surgery
Show all 42Show fewer
  • Age ≥ 20 years
  • Karnofsky Performance Status ≥ 60%
  • Adequate bone marrow reserves within 2 weeks prior to registration, defined as:
  • white blood cells (WBC) ≥ 4,000/µl or neutrophil count (ANC) ≥ 2,000/µl
  • platelets ≥ 100,000/µl
  • hemoglobin ≥ 9.0 g/dl
  • Adequate liver function reserves within 2 weeks prior to registration, defined as:
  • hepatic transaminases ≤ 2.5 x upper limit of normal (ULN)
  • serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Adequate renal function within 2 weeks prior to registration: Creatinine ≤1.5 mg/dL
  • International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN within 2 weeks prior to registration
  • Women of childbearing potential and male participants must practice adequate contraception
  • Patients must be able to comply with the study protocol and follow-up schedules and provide study-specific informed consent
  • Exclusion criteria Patients fulfill any of the following criteria will be excluded from this trial
  • Prior radiotherapy to head and neck, chest, or abdomen
  • Tumor invasion to adjacent structures (T4 lesion)
  • Presence of distant metastasis
  • Adenocarcinoma of gastroesophageal junction.
  • Synchronously or metachronously diagnosed squamous cell carcinoma of aerodigestive way, other than oesophageal cancer
  • Prior invasive malignancy
  • Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:
  • Uncontrolled active infection requiring intravenous antibiotics at the time of registration
  • Transmural myocardial infarction ≤ 6 months prior to registration
  • Unstable angina or congestive heart failure requiring hospitalization ≤ 6 months prior to registration
  • Life-threatening uncontrolled clinically significant cardiac arrhythmias
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  • Uncontrolled psychiatric disorder
  • On full-dose anticoagulants (e.g., Warfarin or low molecular weight heparin) or medications known to inhibit platelet function (e.g. aspirin, dipyramidole, ticlopidine, clopidogrel, cilostazol, or NSAIDs)
  • Prior history of hypertensive crisis or blood pressure at baseline > 150/100 mmHg
  • Hepatic insufficiency resulting in coagulation defects
  • History of a non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to registration
  • Any hemorrhage/bleeding event CTCAE, ver. 4 grade 3 or greater within 30 days prior to registration
  • Gross hemoptysis or hematemesis (defined as bright red blood of 1 teaspoon or more or frank clots within minimal or no phlegm per coughing episode) within 4 weeks prior to registration; patients with incidental blood mixed with phlegm are not excluded.
  • Major surgical procedure or significant traumatic injury within 28 days prior to registration (with the exception of jejunostomy or port-A insertion)
  • Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

Feng-Ming Hsu contact

+886-2-23123456 ext. 67061

hsufengming@ntuh.gov.tw

Jason Chia-Hsien Cheng contact

+886-2-23123456 ext. 66696

Taiwan1 site, 1 recruiting

  • National Taiwan University Hospital

    Taipei, 100

    Jason Chia-Hsien Cheng, +886-2-23123456 ext. 66696, jasoncheng@ntu.edu.tw

    Recruiting

Other trials in Taiwan

About this study

Official title: A Randomized Trial of Adding Bevacizumab to Neoadjuvant Platinum-Fluorouracil Concurrent Chemoradiation in Locally Advanced Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the ten leading cancers in Taiwanese male. The prognosis is poor with a five-year overall survival rate of 10 to 30 %. Randomized clinical trials have demonstrated that trimodality therapy (TMT), consisted of neoadjuvant concurrent chemoradiation (CCRT) and radical esophagectomy, improves the overall survival for patients with locally advanced disease. Despite of the advancement, the outcome remained unsatisfactory with the median progression-free survival around 20 to 25 months and median overall survival around 30 months. It is know that the most important prognostic factor is whether a pathological complete response can be achieved after neoadjuvant CCRT. However, the use of new generation chemotherapeutic agent taxanes and epidermal growth factor inhibitors (such as Cetuximab) failed to significantly improve prognosis comparing to the standard platinum-fluorouracil (PF) regimen. As a consequence, it is mandatory to develop new chemotherapeutic regimen for CCRT.

In previous prospective studies, investigators used proximal ligation assay technology to identify serum VEGF-A in correlation with the pathological response and prognosis for patients receiving neoadjuvant CCRT plus radical esophagectomy for locally advanced ESCC. Other investigators also showed high VEGF expression correlating to poor outcome. Therefore, investigators generate the hypothesis that adding vascular endothelial growth factor (VEGF) monoclonal antibody, Bevacizumab, to standard neoadjuvant CCRT may improve outcome for patients with ESCC. Meanwhile, several prospective clinical studies have shown the feasibility, safety, and activity of adding Bevacizumab to chemotherapy, CCRT, or combined modality therapy including surgery, either in head and neck cancer, esophageal cancer, or esophagogastric junction adenocarcinoma. However, its efficacy should be further investigated in larger prospective trials and little is known about the activity and toxicity of Bevacizumab in ESCC due to small number of reported cases. In the present clinical trial, investigators plan to investigate whether incorporation of Bevacizumab into standard neoadjuvant PF-CCRT will improve treatment response and increase pathological complete response rate. Investigators will also evaluate associated biomarkers in relation to prognosis. By the present research, investigators expect to develop a new TMT regimen for this poor prognostic disease.

Read the detailed description

This study is a randomized trial to compare the outcomes between patients receiving neoadjuvant PF-CCRT plus Bevacizumab (BPF-CCRT) or PF-CCRT alone. Investigators design to enrol 6 patients in the run-in phase, and 44 patients in the randomized phase (22 patients in each group) to develop the preliminary evidence for using Bevacizumab in ESCC.

Being tested
BPF-CCRT (run-in), BPF-CCRT (randomized), PF-CCRT (randomized)
Keywords
Concurrent chemoradiation, Esophageal squamous cell carcinoma, Vascular endothelial growth factor
Medical subject headings
Esophageal Squamous Cell Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BPF-CCRT (run-in)Drug

    Also called Bevacizumab, Cisplatin, 5-Fluorouracil, Radiation

    Six patients will be enrolled in run-in phase. If <= 1 patient developed dose-limiting toxicity, the trial will be continued to randomized phase. If > 1 patients developed dose-limiting toxicities, the protocol will be discontinued.

  • BPF-CCRT (randomized)Drug

    Also called Bevacizumab, Cisplatin, 5-Fluorouracil, Radiation

    Twenty-two patients will be planned to assign to the experimental arm

  • PF-CCRT (randomized)Drug

    Also called Cisplatin, 5-Fluorouracil, Radiation

    Twenty-two patients will be planned to assign to the active control arm

Study groups in NCT02812641
Study groupRoleWhat they receive
BPF-CCRT (Run-in Phase)ExperimentalNeoadjuvant CCRT with Bevacizumab, Cisplatin and 5-fluorouracil Chemotherapy: Bevacizumab(B): 10 mg/kg on day 1 Cisplatin(P): 75 mg/m2 on day 1 5-fluorouracil(F): 24 hours continuous infusion of 1,000 mg/m2 on days 1-4 Radiotherapy: 40 Gy/20 fractions: days 1-5, weeks 1-4
Receives: Drug: BPF-CCRT (run-in)
BPF-CCRT (Randomized Phase)ExperimentalNeoadjuvant CCRT with Bevacizumab, Cisplatin and 5-fluorouracil Chemotherapy: Bevacizumab(B): 10 mg/kg on day 1 Cisplatin(P): 75 mg/m2 on day 1 5-fluorouracil(F): 24 hours continuous infusion of 1,000 mg/m2 on days 1-4 Radiotherapy: 40 Gy/20 fractions: days 1-5, weeks 1-4
Receives: Drug: BPF-CCRT (randomized)
PF-CCRT (Randomized Phase)Active comparatorNeoadjuvant CCRT with Cisplatin and 5-fluorouracil Chemotherapy: Cisplatin(P): 75 mg/m2 on day 1 5-fluorouracil(F): 24 hours continuous infusion of 1,000 mg/m2 on days 1-4 Radiotherapy: 40 Gy/20 fractions: days 1-5, weeks 1-4
Receives: Drug: PF-CCRT (randomized)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity (run-in phase)

    Number of participant in the run-in phase with life-threatening adverse event or death, which is probable or definitely associated with bevacizumab

    Measured: 30 days after radical esophagectomy

  2. Pathological complete response rate (randomized phase)

    Number of participant achieved pathological complete response, which is defined as complete surgical resection of all gross tumours without residual microscopic invasive carcinoma at primary tumor location and dissected lymph nodes.

    Measured: 8 weeks

Secondary outcomes (8)

  1. Acute toxicity

    Common Toxicity Criteria for Adverse Events version 4

    Measured: From date of CCRT until 90 days after CCRT starts

  2. Late toxicity

    Common Toxicity Criteria for Adverse Events version 4

    Measured: From 90 days after CCRT starts until the date of death from any cause, up to 60 months

  3. Patient reported outcome (Quality of Life questionnaire of cancer patients)

    EORTC Quality of Life-Core 30 questionnaire module

    Measured: At baseline, 2, 4 weeks after CCRT, before surgery, 1 month after surgery, and every 3 month thereafter until unequivocal progression, hospice care, or death, assessed up to 24 months

  4. Patient reported outcome (Quality of Life questionnaire of esophageal cancer patients)

    EORTC Quality of Life-Oesophagus(OES) 18 questionnaire module

    Measured: At baseline, 2, 4 weeks after CCRT, before surgery, 1 month after surgery, and every 3 month thereafter until unequivocal progression, hospice care, or death, assessed up to 24 months

  5. Image response

    Response Evaluation Criteria In Solid Tumors version 1.1

    Measured: at baseline and before surgery (8 weeks)

  6. Metabolic Image response

    Positron Emission Tomography Response Criteria in Solid Tumors version 1.0

    Measured: at baseline and before surgery (8 weeks)

  7. Progression-free survival

    Number of participant with disease progression

    Measured: From date of enrolment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 60 months

  8. Overall survival

    Number of participant alive

    Measured: From date of enrollment until the date of death from any cause, assessed up to 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jun 2016 (estimated)
  2. Study startJun 2016
  3. Primary completionDec 2019 (estimated)
  4. Study completionDec 2021 (estimated)

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02812641
Sponsor's protocol ID
201511008MINC
Status last verified
Mar 2019
First submitted
13 Jun 2016
Last updated
11 Mar 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BPF-CCRT (run-in), BPF-CCRT (randomized) and PF-CCRT (randomized) in people with Stage III Esophageal Squamous Cell Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.

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 42 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 11 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Taiwan. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Feng-Ming Hsu (+886-2-23123456 ext. 67061, hsufengming@ntuh.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity (run-in phase) (time frame: 30 days after radical esophagectomy). The study lists 2 primary outcomes in all. 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 NCT02812641.

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 11 Mar 2019.

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