Clinical trial NCT02017600: A Phase II Trial of Induction Chemotherapy With ND-420, Cisplatin and Fluorouracil Followed by Surgery in the Treatment of Patients With Localized Squamous Cell Carcinoma of the Esophagus
Official title: A Phase II Trial of Induction Chemotherapy With ND-420, Cisplatin and Fluorouracil Followed by Surgery in the Treatment of Patients With Localized Squamous Cell Carcinoma of the Esophagus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Localized Squamous Cell Carcinoma of the Esophagus
Lead sponsor: Nang Kuang Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2013-12-23
Enrollment: 48
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Investigator will assign 53 patients who had been histologically proven localized squamous cell carcinoma of esophagus to receive the induction chemotherapy regimen of ND-420 50 mg/m2 on day 1, cisplatin 70 mg/m2 on day1, plus fluorouracil 700 mg/m2 daily, day1 to day4, every 3 weeks for 2 cycles and then followed by surgical resection. The successful rate of complete treatment per protocol and complete resection will be the primary variant to evaluate in our study.


Eligibility criteria: Inclusion Criteria:

* Patients must have been histologically proven esophageal carcinoma (squamous cell carcinoma).
* The tumor had to be locally advanced (stage T2-3/N0, T1-3/N+, if technically resectable with curative intent).
* Patients must be 20 years of age.
* Patients must have an ECOG performance status score 2.
* Patients must have a life expectancy of at least 12 weeks.
* Patients must be accessible for treatment and follow-up at least for one year.
* Patients must sign the informed consent form.
* Patient must have:Hemoglobin level 9 g/dl; Neutrophil count 1,500/mm3; Platelets count 100,000/mm3; Serum bilirubin level 1.0 ULN; Serum transaminase (GOT, GPT) levels 2.0 ULN; Serum Alkaline phosphatase levels 2.0 ULN; Serum creatinine level 1.5 mg/dl or Creatinine clearance rate(CrCl)60 ml/min for the institution (calculated by the Cockcroft- Gault equation).

Exclusion Criteria:

* Patient who are receiving or had received concurrent radiotherapy, chemotherapy or other anticancer treatment for esophageal carcinoma.
* Patients with known history of severe hypersensitivity reactions to any medicine or to drugs formulated with polysorbate 80.
* Major surgery within two weeks prior to entering the study, excluding port-A insertion or feeding jejunostomy surgery.
* Patients with CNS metastasis, including clinical suspicion.
* Patients with clinically detectable peripheral neuropathy 2 on the CTC criteria.
* Mental statuses of patients are not fit for clinical trial.
* Fertile men and women unless using a reliable and appropriate contraceptive method.
* Patients with pregnancy or lactating, women considering pregnancy, possible pregnancy that without using effective contraception.
* Patients who have serious concomitant illness that might be aggravated by chemotherapy, as below included:Active cardiac disease (e.g. congestive heart failure, angina, arrhythmia, acute myocardial disease or other types of heart disease requiring treatment) within 6 months period preceding entry into the study; Uncontrolled infection (e.g. active infection that uncontrolled for 2 weeks under antibiotic therapy); Retention of body fluid (e.g. pleural effusion, ascites, pericardial effusion, and edema needing treatment); History of other than esophageal cancer, except curatively treated non-melanoma skin cancer or in situ carcinoma of the esophagus; and other conditions which will be judged by physician's discretion.

Primary outcomes:
measure: the R0 resection rate of participants
timeFrame: up to three months
Secondary outcomes:
measure: the response rate (RECIST) of participants
timeFrame: up to three months
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: up to one year
measure: the population pharmacokinetic parameters (Cmax, AUC... )of ND-420 in the participants
timeFrame: 0, 30min, 1hr of ND-420 infusion. selected randomly form one of 3hr, 7hr, 11hr and 23hr after the end of ND-420 infusion.
measure: the correlation between clinical outcomes and the potential predictive genomic biomarkers(B-tubulin mutation, p53-Arg 72Pro, Bcl2-C938A, MDR1-C3435T polymorphism, TNFRSF1B-1466, GSTP1-l105V, CYP1B1, TS-5'UTR) for tumor response
timeFrame: up to one year
measure: 1-year survival rate of participants
timeFrame: up to one year
measure: pathologic complete response rate of participants
timeFrame: up to one year
measure: 1-year progression free survival rate of participants
timeFrame: up to one year
measure: 1-year overall survival rate of participants
timeFrame: up to one year
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Taipei Veterans General Hospital, Taiwan
name: Ming-Huang Chen, M.D.
role: PRINCIPAL_INVESTIGATOR
References: