Clinical trial NCT03188497: Dose Escalation of Lobaplatin Concurrent With IMRT for the Treatment of NPC: A Phase I 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Toxic Effects
Tumor Responses
Lead sponsor: Fifth Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2017-06-15
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Platelets
timeFrame: 1 years
measure: Leukocytes
timeFrame: 1 years
measure: Neutrophils
timeFrame: 1 years
measure: Hemoglobin
timeFrame: 1 years
Secondary outcomes:
measure: Nausea
timeFrame: 1 years
measure: Vomiting
timeFrame: 1 years
Other outcomes:
measure: Aspartate transaminase (ALT)
timeFrame: 1 years
measure: Aspartate transaminase (AST)
timeFrame: 1 years
measure: Bilirubin
timeFrame: 1 years
measure: Glutamyl transpeptidase (GGT)
timeFrame: 1 years
measure: Alkaline phosphatase (ALP)
timeFrame: 1 years
measure: Creatinine（CRE）
timeFrame: 1 years
Locations:
city: Zhuhai
country: China
facility: the Fifth Hospital Affiliated to Sun Yat-Sen University
state: Guangdong
Study officials:
affiliation: Fifth Hospital Affiliated to Sun Yet Sen universty
name: Siyang Wang, bachelor
role: STUDY_DIRECTOR
References:
citation: 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.