Dose Escalation of Lobaplatin Concurrent With IMRT for the Treatment of NPC: A Phase I Clinical Trial

Study Overview
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Brief Summary
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Nasopharyngeal carcinoma (NPC) is a common malignant tumor in Southern China area, which is characterized by obvious regional characteristics and Guangdong cancer. Radiotherapy is the main treatment for locally advanced nasopharyngeal carcinoma. In recent years, chemotherapy has improved the short-term and long-term survival of patients with locally advanced nasopharyngeal carcinoma. Lobaplatin is the third generation platinum anticancer drugs, mechanism of action and traditional cisplatin is similar, mainly formed by the Pt-GG and Pt-AG chain cross connect, replication and transcription process blocks of deoxyribonucleic acid(DNA), thereby interfering with tumor cell cycle. The damage of DNA induced by lobaplatin can influence the expression of tumor cell specific genes. Due to the different structure of lobaplatin and no cross resistance to cisplatin in the study showed that, compared with cisplatin with gastrointestinal reaction more mild, and no cisplatin common liver and kidney toxicity, neurotoxicity and ototoxicity, in some tumors have a better adaptability; but compared with cisplatin had more severe bone marrow suppression this, offset some of the advantages of lobaplatin in a certain extent. At present, the clinical indications for the treatment of such diseases include head and neck cancer, breast cancer, gastrointestinal cancer, gynecologic malignant tumor and non small cell lung cancer. Tian Ying confirmed that lobaplatin has obvious cytotoxic effect on nasopharyngeal carcinoma cells, in a concentration dependent manner, the mechanism for the dual role, namely block at lower concentration of cells in G2 phase and induce apoptosis at higher concentration, provide the possibility for clinical treatment of nasopharyngeal carcinoma for lobaplatin; there are a number of clinical study confirmed that lobaplatin chemoradiotherapy for locally advanced nasopharyngeal carcinoma with cisplatin approximation. But at present, there is no report on the dose and tolerability of concurrent radiotherapy for nasopharyngeal carcinoma. Therefore, a dose escalation trial was conducted to determine maximum tolerated dose of lobaplat in as a single agent combined with concurrent intensity-modulated radiotherapy in a Chinese population with locoregionally advanced NPC.

Official Title
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Dose Escalation of Lobaplatin Concurrent With Intensity-modulated Radiotherapy for the Treatment of Stage III-IVb Nasopharyngeal Carcinoma: A Phase I Clinical Trial in an Asian Population

Conditions
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Acute Toxic Effects, Tumor Responses

Intervention / Treatment
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* Drug: Lobaplatin
* Device: linear accelerator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The pathological type is non keratinized carcinoma (according to the pathological classification of World, Health, Organization, WHO) Overall Stage III-IVB (according to the seventh edition of AJCC staging system). Age between 18-65 years old. There is no evidence of distant metastasis. Eastern Cooperative Oncology Group performance status 0 or 1. Normal marrow function: white blood count > 4 * 109/L, hemoglobin > 90g/L, and platelet count > 100 * 109/L. Normal liver function: total bilirubin (TBIL) and alanine aminotransferase (ALT) <2 times the normal values. Normal renal function: creatinine (Cr) <1.5 times the normal value. The patient must be the basic content of this research and the defendant signed the informed consent. Exclusion Criteria: The pathological type is WHO squamous cell carcinoma or squamous cell carcinoma. Age > 65 years old, or < 18 yeas old. The purpose of treatment is palliative. There was a history of malignancy, except for adequately treated basal cell carcinoma or squamous cell carcinoma, and carcinoma in situ of the cervix. Women who are pregnant or lactating (for women of child-bearing age) should consider pregnancy tests; effective contraception should be emphasized during treatment）. Previously received radiation therapy . Primary and neck metastases were treated with chemotherapy or surgery. Accompanied by other serious diseases may pose a greater risk or impact on test compliance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Sequential Assignment
Interventional Model Description: The initial dose was 25mg/m2 on d1,d22,d43 for 1 cycles; if no obvious toxicity was observed,follow 30mg/m2,35mg/m2,40mg/m2,45mg/m2, and 50mg/m2 gradients into the next dose group until the maximum tolerated dose or 50mg/m2
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experience group 1<br>The dose of lobaplatin is 25mg/m2 on d1,d22,d43. | Drug: Lobaplatin<br>* Lobaplatin for Injection<br>Device: linear accelerator<br>* Medical linear accelerator<br>|
| Experimental: Experience group 2<br>The dose of lobaplatin is on d1,d22,d43. | Drug: Lobaplatin<br>* Lobaplatin for Injection<br>Device: linear accelerator<br>* Medical linear accelerator<br>|
| Experimental: Experience group 3<br>The dose of lobaplatin is on d1,d22,d43. | Drug: Lobaplatin<br>* Lobaplatin for Injection<br>Device: linear accelerator<br>* Medical linear accelerator<br>|
| Experimental: Experience group 4<br>The dose of lobaplatin is 40mg/m2 on d1,d22,d43. | Drug: Lobaplatin<br>* Lobaplatin for Injection<br>Device: linear accelerator<br>* Medical linear accelerator<br>|
| Experimental: Experience group 5<br>The dose of lobaplatin is 45mg/m2 on d1,d22,d43. | Drug: Lobaplatin<br>* Lobaplatin for Injection<br>Device: linear accelerator<br>* Medical linear accelerator<br>|
| Experimental: Experience group 6<br>The dose of lobaplatin is 50mg/m2 on d1,d22,d43. | Drug: Lobaplatin<br>* Lobaplatin for Injection<br>Device: linear accelerator<br>* Medical linear accelerator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelets | grade 3: 25.0-< 50.0*109/L; grade 4:< 25.0*109/L. | 1 years | 
| Leukocytes | grade 3: 1.0-< 2.0*10^9/L; grade 4: < 1.0*10^9/L. | 1 years | 
| Neutrophils | grade 3: 0.5-< 1.0*10^9/L; grade 4: < 0.5*10^9/L. | 1 years | 
| Hemoglobin | grade 3: < 80 g/L; transfusion indicated; grade 4:Life-threatening consequences; urgent intervention indicated; grade 5: Death | 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nausea | grade 3: Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated | 1 years | 
| Vomiting | grade 3: > 6 episodes (separated by 5 minutes) in 24 hrs; tube feeding, TPN, or hospitalization indicated; grade 4:Life-threatening consequences; urgent intervention indicated; grade 5: Death. | 1 years |