Clinical trial NCT03791151: Pharmacogenetics in Non Small Cell Lung Cancer
Official title: Effect of Copper Transporter-1 Genetic Polymorphism on Platinum Based Chemotherapy Response in Advanced Non-Small Cell Lung Cancer Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Non Small Cell Lung Cancer
Keywords: Pharmacogenetics
Lung cancer
Cisplatin
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2019-01-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newly diagnosed with immunohistochemically and pathologically confirmed non- small cell lung cancer (NSCLC).

Brief summary: Study the effect of genetic polymorphism in the membrane copper transporter 1 protein \[CTR1; encoded by the solute carrier family 31 member 1 gene (SLC31A1 gene)\] and its genetic expression levels on the clinical outcome of cisplatin-based regimen used in the treatment of Non-Small Cell Lung Cancer (NSCLC) in terms of :

* Treatment response : partial response (PR) / complete response (CR) and Progression-free survival (PFS)
* Treatment resistance : stationary disease (SD) or progressed disease
* Frequency and severity of regimen related toxicity

Detailed description: The cisplatin-based regimen is an effective treatment for advanced NSCLC, showing significant beneficial outcomes such as prolong survival, improve clinical symptoms, and improve quality of life (QOL) . Although platinum-based therapy shows several benefits, but the five-year survival rate still less than 20%.

Pt resistance is an inevitable occurrence with rare exception. Aside from germ cell tumors, metastatic solid tumors are generally thought to be incurable with cytotoxic chemotherapy due to the development of resistance and subsequent disease progression.

Despite the multifactorial nature of Cisplatin resistance, intracellular accumulation of Pt appears to be a major source of drug resistance . Reduced intracellular drug accumulation is one of the most consistently identified features of cisplatin-resistant cells.

Many evidences indicated that alteration of copper transporter protein 1 (CTR1) which is the major plasma membrane transporter responsible for platinum uptake, was associated with platinum sensitivity and toxicity.

Genetic polymorphisms of CTR1 also have effects to platinum treatment response. Therefore, CTR1 might be a potential prognostic factor for survival in cancer patients underwent chemotherapy and a treatment target for overcoming platinum resistance.

Eligibility criteria: Inclusion Criteria:

1. Newly diagnosed with immunohistochemically and pathologically confirmed non- small cell lung cancer (NSCLC).
2. ECOG PS 0-2.
3. Chemotherapy naïve.
4. Age \>18 years.
5. Adequate bone marrow reserve.

Exclusion Criteria:

1. Presence of central nervous system metastases.
2. Inadequate liver function (bilirubin \> 1.5 times upper normal limit \[ULN\] and alanine transaminase \[ALT\] or aspartate transaminase \[AST\] \> 3.0 ULN or up to 5.0 UNL in the presence of hepatic metastases).
3. Inadequate renal function (creatinine \> 1.25 times ULN, creatinine clearance \< 50mL/min).
4. Serious comorbid systemic disorder incompatible with the study.
5. Second primary malignancy (except in situ carcinoma of the cervix, adequately treated basal cell carcinoma of the skin, T1 vocal cord cancer in remission, or prior malignancy treated more than 5 years prior to enrollment without recurrence).
6. Pregnancy

Primary outcomes:
measure: Tumor response and resistance
timeFrame: 1 year
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 1.5 years
measure: Regimen related toxicity
timeFrame: 1.5 years
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain Shams University's Hospital
Study officials:
References:
citation: Blair BG, Larson CA, Safaei R, Howell SB. Copper transporter 2 regulates the cellular accumulation and cytotoxicity of Cisplatin and Carboplatin. Clin Cancer Res. 2009 Jul 1;15(13):4312-21. doi: 10.1158/1078-0432.CCR-09-0311. Epub 2009 Jun 9.
citation: Roco A, Cayun J, Contreras S, Stojanova J, Quinones L. Can pharmacogenetics explain efficacy and safety of cisplatin pharmacotherapy? Front Genet. 2014 Nov 14;5:391. doi: 10.3389/fgene.2014.00391. eCollection 2014.
citation: Xu X, Ren H, Zhou B, Zhao Y, Yuan R, Ma R, Zhou H, Liu Z. Prediction of copper transport protein 1 (CTR1) genotype on severe cisplatin induced toxicity in non-small cell lung cancer (NSCLC) patients. Lung Cancer. 2012 Aug;77(2):438-42. doi: 10.1016/j.lungcan.2012.03.023. Epub 2012 Apr 17.