Efficacy and Safety of TC+AVASTIN Versus TC in Patients With Metastatic Nasopharyngeal Carcinoma

Nasopharyngeal Neoplasms Clinical Trial

Official title:

Multi-center, Randomized, Controlled, Open-label Study of Bevacizumab With Carboplatin and Paclitaxel Versus Carboplatin and Paclitaxel in Patients With Metastatic Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02250599
• Other study ID #: ML29153
• Status: Recruiting
• Phase: Phase 2
• First received: August 26, 2014
• Last updated: December 28, 2015
• Start date: August 2014
• Est. completion date: December 2016

Study information

• Verified date: December 2015
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The present study will be a randomized, control, multicenter phase II study of metastatic nasopharyngeal carcinoma (NPC) treated with evacizumab (AVASTIN,Roch) with paclitaxel and carboplatin regimen (TC+AVASTIN) or carboplatin/paclitaxel alone (TC). The population consists of metastatic nasopharyngeal carcinoma (NPC) that failed the radical radiotherapy or chemotherapy-naïve advanced NPC (stage IV). The effectiveness and side effects will be evaluated according to RECIST 1.1 and NCI-CTC AE V4.0.TEORTC QLQ-C30 and EORTC QLQ-H&N35 are used to measure PRO outcome for this study.

Description:

Nasopharyngeal carcinoma is vastly more common in East Asia, especially China has a high incidence of it, and the number of new cases will account for more than 40% of the world total . The disease involved population maybe more than 4 million in the world. More than 2700-3000 new nasopharyngeal carcinoma patients will be diagnosed in SUN YAT-SEN university cancer center every year. It is most common in 40-50 years old adults and has been a top ten (10th) malignant tumor in Chinese male which threaten human health and social economy.

Chemotherapy is the standard treatment of the advanced nasopharyngeal carcinoma.Several other phase II study also confirmed the effectiveness of paclitaxel and carboplatin （TC） regimen in advanced NPC, so it maybe a simple right choice.

Increasing expression of VEGF in serum associated with poor prognosis in metastatic nasopharyngeal carcinoma. Agents that selectively target VEGF-A and its receptors have shown significant antitumor effects in xenograft models of nasopharyngeal. Studies demonstrated that bevacizumab（AVASTIN） administration with chemotherapy or chemoradiation is feasible in patients with nasopharyngeal cancer. Bevacizumab can be safely combined with a range of cytotoxic and other anticancer agents including TC regimen.

Evidence indicated a potential possibility that the TC+AVASTIN regimen may be superior than TC regimen.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must meet the following criteria for study entry:

• Age = 18

• Eastern Cooperative Oncology Group (ECOG) performance status 0~1

• Patients with a life expectancy>12 weeks

• Histologically proven NPC diagnosis

• Metastatic nasopharyngeal carcinoma with evidence of unsuitable for local treatment(in terms of some relevant therapy for anti-tumor like surgery, radiofrequency ablation, transcatheter arterial chemoembolization(TACE) and radiotherapy(except palliative radiotherapy for metastatic bone pain with appropriate radiation dosage without influence to the hemogram),etc.)

• Neoadjuvant or concurrent chemoradiotherapy was allowed, provided that the treatment was completed at least 3 months before the start of study drug treatment

-=1 measurable target based on RECIST criteria

• Adequate bone marrow, hepatic and renal function, defined as follows within 1 weeks prior to randomization

• Patients must sign study specific informed consent prior to registration

• Patient must have recovered (be >28 days post-surgery) from the effects of surgery, postoperative infection, and other complications before initial treatment with bevacizumab

• Systolic blood pressure = 160 mmHg and diastolic pressure = 90 mmHg within 7 days prior to randomization.

Exclusion Criteria:

• Prior systemic treatment for metastatic nasopharyngeal carcinoma

• Preparing for receiving local treatment for metastatic nasopharyngeal carcinoma (excluding palliative irradiation to release skeletal pain)

• Prior treatment with bevacizumab or other agents specifically targeting VEGF

• Patients with hemorrhage tendency including acute hemorrhage of digestive tract, nasal bleeding (not including nasal epistaxis), continuous hemorrhagic disease or Coagulation function disorder disease. Patients are using known NSAIDS to inhibit platelets.

• Patients with 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

• Patients receiving other experimental therapeutic cancer treatment

• Severe, active co-morbidity, defined as follows:

i.--Unstable angina and/or congestive heart failure or vascular (e.g. aortic aneurysm requiring surgical repair or peripheral thrombosis) disease requiring hospitalization within the last 12 months, or other cardiac compromise (e.g. an inadequately controlled cardiac arrhythmia) that in the judgment of the investigator will preclude the safe administration of a study drug; Patient must not show sign of recent myocardial infarction or ischemia by the findings of S-T elevations of = 2mm on an EKG ii.--History of arterial thromboembolic events, venous thromboembolism >NCI CTCAE Grade 3, transient ischemic attack (TIA), cerebral vascular accident (CVA), transmural myocardial infarction (MI), or hypertensive crisis or hypertensive encephalopathy iii.--History of ongoing bleeding diathesis, hemorrhagic disorder, or coagulopathy iv.--Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration v.--History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or active GI bleeding within the last 6 months prior to registration; vi.--Esophageal varices, non-healing ulcer, non-healing wound, or bone fracture within the last 6 months prior to registration vii.--Active, untreated infection and/or acute bacterial or fungal infection uiring intravenous antibiotics at the time of registration viii.--Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; ix. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects x. - Minor surgical procedure including placement of a vascular access device, within 2 days of the first study treatment

• Patients currently (within 10 days of study enrollment) taking warfarin, heparin, daily treatment with aspirin (> 325 mg/day), or nonsteroidal anti-inflammatory medications known to inhibit platelet function; treatment with dipyramidole, ticlopidine, clopidogrel, or cilostazol

• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception;

• Prior allergic reaction to the study drug(s) involved in this protocol

• Contraindication to Bevacizumab

• Patients has another cancer history (not NPC)within 5 years before randomization.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Nasopharyngeal Neoplasms

Intervention

Drug:
• Paclitaxel
Paclitaxel 175 mg/m2 IV Day 1 each 3-week cycle
• Bevacizumab
Bevacizumab 7.5 mg/kg Day 1 each 3-week cycle
• Carboplatin
Carboplatin AUC 6 IV Day 1 each 3-week cycle

Locations

Country	Name	City	State
China	Dongguan People`s Hospital	Dongguan	Guangdong
China	Department of Medical Oncology,Cancer Center of Sun Yat-Sen University	Guangzhou	Guangdong
China	First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine	Guangzhou	Guangdong
China	Guangzhou University of Chinese Medicine	Guangzhou	Guangdong
China	Hainan General Hospital	Haikou	Hainan
China	Jiangmen Central Hospital	Jiangmen	Guangdong
China	The People`s Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi
China	Shenzhen People`s Hospital	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival(PFS)		3 years	No
Secondary	Overall survival(OS)		3 years	No
Secondary	Overall response rate (ORR,CR+PR)	Identified by investigators and independent radiologic review (IRC) respectively	3 years	No
Secondary	Disease control rate(DCR,CR+PR+SD)	Identified by investigators and IRC respectively	3 years	No
Secondary	Health-related quality of life		3 years	No
Secondary	Number of Participants with Adverse Events		3 years	Yes
Secondary	Progression free survival(PFS)	Identified by IRC	3 years	No