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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Toxic Effects; Tumor Responses
• Intervention / Treatment: Drug: Lobaplatin; Device: linear accelerator

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Zhuhai, Guangdong, China, 519000
      • the Fifth Hospital Affiliated to Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: SINGLE

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aspartate transaminase (ALT)	ALT: grade 3: > 5.0-20.0*ULN; grade 4: > 20.0*ULN.	1 years
Aspartate transaminase (AST)	grade 3: > 5.0-20.0*ULN; grade 4: > 20.0*ULN.	1 years
Bilirubin	grade 3: > 3.0-10.0*ULN; grade 4: > 10.0*ULN.	1 years
Glutamyl transpeptidase (GGT)	grade 3: > 5.0-20.0*ULN; grade 4: > 20.0*ULN.	1 years
Alkaline phosphatase (ALP)	grade 3:> 5.0-20.0*ULN; grade 4: > 20.0*ULN.	1 years
Creatinine（CRE）	grade 3: > 3.0-6.0*ULN, > 3.0 baseline; grade 4: > 6.0*ULN.	1 years

Collaborators and Investigators

• Sponsor: Fifth Affiliated Hospital, Sun Yat-Sen University
• Investigators: Study Director: Siyang Wang, bachelor, Fifth Hospital Affiliated to Sun Yet Sen universty

Publications and helpful links

General Publications

• Wang SY, Xu XW, Yao JJ, Peng PJ, Zhou B, Liu QD, Huang XP, Lin Z. Dose Escalation of Lobaplatin Concurrent with IMRT for the Treatment of Stage III-IVb NPC: A Phase I Clinical Trial. Transl Oncol. 2018 Aug;11(4):1007-1011. doi: 10.1016/j.tranon.2018.06.004. Epub 2018 Jun 29.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 22, 2016
• Primary Completion (ACTUAL): December 12, 2017
• Study Completion (ACTUAL): March 20, 2018

Study Registration Dates

• First Submitted: May 22, 2017
• First Submitted That Met QC Criteria: June 13, 2017
• First Posted (ACTUAL): June 15, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 10, 2018
• Last Update Submitted That Met QC Criteria: April 7, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: zsu20170203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No