Clinical trial NCT01735409: Dose-finding Study of Abraxane in Combination With Cisplatin to Treat Advanced Nasopharyngeal Carcinoma
Official title: A Single Center Phase IIa Study of Nanoparticle Albumin-bound Paclitaxel in Combination With Cisplatin in Advanced Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Nasopharyngeal Neoplasms
Keywords: Advanced Nasopharyngeal Carcinoma
Abraxane
Cisplatin
Dose
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2012-11-28
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single center, non-randomized phase IIa study to determine the tolerance and safety of Abraxane (ABX) in combination with cisplatin (DDP) in patients with advanced nasopharyngeal carcinoma (NPC). Patients in whom the standard therapy had failed or had been infeasible will be eligible.The safety and efficacy will be evaluated according to NCI-CTCAE V4.0 and RECIST 1.1 respectively.

Detailed description: Nasopharyngeal carcinoma (NPC) is most commonly seen in Southeast Asia, especially in southern and southeastern China, where the incidence rate has been documented between 10 and 150 cases per 100,000 population per year. For advanced or metastatic NPC, chemotherapy remain the mainstay of treatment. The 130-nm albumin-bound formulation of paclitaxel (\[Abraxane, ABX \];Celgene,Summit,NJ) is a promising new agent with more efficient entry to the tumor microenvironment via caveolae-mediated transcytosis and preferential uptake by cancer cells. Superior activity of ABX-based regimens without the necessity for antianaphylactic pretreatments been shown in various solid tumors compared with the traditional solvent-based paclitaxel-based ones. However, the safety and efficacy of combination of ABX and cisplatin (DDP) has not been determined in patients with advanced NPC. In this single center, non-randomized phase IIa study, investigators seek to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of ABX-DDP, and perform an exploratory study of its efficacy as measured by tumor response.

Eligibility criteria: Inclusion Criteria:

* Histologically proven NPC diagnosis
* Patients who failed the prior standard treatment or were intolerant of standard treatment
* Elder than 18 years old
* Performance status 0-2
* Patients previously treated with chemotherapy (those having received paclitaxel-based regimen were not excluded)
* Subjects with at least one measurable lesion (Tumor lesions that are situated in a previously irradiated area could not be considered measurable).
* Life expectancy over twelve weeks
* Neutrophil \> 1.5X10\^9/L, PLT \> 100X10\^9/L, Hb ≥ 90 g／l, with normal hepatic function(AST, ALT \< 2.5 x upper limit of normal , and bilirubin \< 1.0 x upper limit of normal), with normal renal function (creatinine \< 1.5 x upper limit of normal or creatinine clearance ≥ 60ml/min as calculated by the Cockcroft - Gault formula. )
* Urine pregnancy test (-) within 1 weeks before enrollment or being able to take effective contraceptive measures during the medication and six months after completion of the trial for fertile women.
* Being able to provide paraffin blocks or 5-7 slides of biopsy tumor tissues.
* Amenable to regular follow-up and to comply with trial requirements.
* Signed and dated informed consent before the start of specific protocol procedures

Exclusion Criteria:

* History of allergy to paclitaxel or docetaxel
* Patient with central nervous system metastasis
* Patient refusing participation or signing informed consent
* Active clinically serious infections with an anticipated antibiotics treatment for more than 4 weeks
* Patient with life threatening medical condition such as congestive heart failure, symptomatic coronary artery disease or heart block
* Myocardial infarction that occurred within 3 months before enrollment
* Had received chemotherapy, radiotherapy or other anti-cancer therapies within 3 weeks before enrollment
* With a pre-existing peripheral neuropathy (National Cancer Institute Common Toxicity Criteria for Adverse Events \[NCI CTC\] grade ≥ 2)
* Previously received post-2nd line anti-cancer therapy
* Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors\[Ta, Tis \& T1\] or any cancer curatively treated \> 3 years prior to study entry.
* History of immunodeficiency , including HIV testing positive or suffering from other acquired and congenital immunodeficiency disease, or the history of organ transplants;
* Patients receiving prior abraxane treatment during pregnancy or lactation period
* Fertile women who failed to or are reluctant to take contraceptive measures or pregnancy test
* Men or his companion who are reluctant to take effective contraceptive measures during the medication and six months after completion of the trial

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 24 months
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: 24 months
measure: Number of Participants with Adverse Events
timeFrame: 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Cancer Center, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Li Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huang Y, Liang W, Yang Y, Zhao L, Zhao H, Wu X, Zhao Y, Zhang Y, Zhang L. Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab(R)-Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma. BMC Cancer. 2016 Jul 13;16:464. doi: 10.1186/s12885-016-2517-5.