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

Tumor Responses Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03188497
• Other study ID #: zsu20170203
• Status: Completed
• Phase: Phase 1
• First received: May 22, 2017
• Last updated: April 7, 2018
• Start date: June 22, 2016
• Est. completion date: March 20, 2018

Study information

• Verified date: April 2018
• Source: Fifth Affiliated Hospital, Sun Yat-Sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: March 20, 2018
• Est. primary completion date: December 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. The pathological type is non keratinized carcinoma (according to the pathological classification of World, Health, Organization, WHO)

2. Overall Stage III-IVB (according to the seventh edition of AJCC staging system).

3. Age between 18-65 years old.

4. There is no evidence of distant metastasis.

5. Eastern Cooperative Oncology Group performance status 0 or 1.

6. Normal marrow function: white blood count > 4 * 109/L, hemoglobin > 90g/L, and platelet count > 100 * 109/L.

7. Normal liver function: total bilirubin (TBIL) and alanine aminotransferase (ALT) <2 times the normal values.

8. Normal renal function: creatinine (Cr) <1.5 times the normal value.

9. The patient must be the basic content of this research and the defendant signed the informed consent.

Exclusion Criteria:

1. The pathological type is WHO squamous cell carcinoma or squamous cell carcinoma.

2. Age > 65 years old, or < 18 yeas old.

3. The purpose of treatment is palliative.

4. There was a history of malignancy, except for adequately treated basal cell carcinoma or squamous cell carcinoma, and carcinoma in situ of the cervix.

5. Women who are pregnant or lactating (for women of child-bearing age) should consider pregnancy tests; effective contraception should be emphasized during treatment).

6. Previously received radiation therapy .

7. Primary and neck metastases were treated with chemotherapy or surgery.

8. Accompanied by other serious diseases may pose a greater risk or impact on test compliance.

Related Conditions & MeSH terms

• Acute Toxic Effects
• Tumor Responses

Intervention

Drug:
• Lobaplatin
Lobaplatin for Injection

Device:
• linear accelerator
Medical linear accelerator

Locations

Country	Name	City	State
China	the Fifth Hospital Affiliated to Sun Yat-Sen University	Zhuhai	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Fifth Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Aspartate transaminase (ALT)	ALT: grade 3: > 5.0-20.0*ULN; grade 4: > 20.0*ULN.	1 years
Other	Aspartate transaminase (AST)	grade 3: > 5.0-20.0*ULN; grade 4: > 20.0*ULN.	1 years
Other	Bilirubin	grade 3: > 3.0-10.0*ULN; grade 4: > 10.0*ULN.	1 years
Other	Glutamyl transpeptidase (GGT)	grade 3: > 5.0-20.0*ULN; grade 4: > 20.0*ULN.	1 years
Other	Alkaline phosphatase (ALP)	grade 3:> 5.0-20.0*ULN; grade 4: > 20.0*ULN.	1 years
Other	Creatinine(CRE)	grade 3: > 3.0-6.0*ULN, > 3.0 baseline; grade 4: > 6.0*ULN.	1 years
Primary	Platelets	grade 3: 25.0-< 50.0*109/L; grade 4:< 25.0*109/L.	1 years
Primary	Leukocytes	grade 3: 1.0-< 2.0*10^9/L; grade 4: < 1.0*10^9/L.	1 years
Primary	Neutrophils	grade 3: 0.5-< 1.0*10^9/L; grade 4: < 0.5*10^9/L.	1 years
Primary	Hemoglobin	grade 3: < 80 g/L; transfusion indicated; grade 4:Life-threatening consequences; urgent intervention indicated; grade 5: Death	1 years
Secondary	Nausea	grade 3: Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated	1 years
Secondary	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