Clinical trial NCT02370017: Combined Effect of Natural Killer Cell and Doublet Chemotherapy in Advanced NSCLC as the 1st Line Treatment
Official title: Combined Effect of Autologous Ex-vivo Expanded Activated NK Cell-lymphocytes (ANKL) and Doublet Chemotherapy in Patients With Advanced NSCLC as the 1st Line Treatment; Phase II
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Autologous Ex vivo-expanded NK cell enriched lymphocytes
Lead sponsor: The Catholic University of Korea
Sponsor class: OTHER
First posted: 2015-02-24
Enrollment: 68
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The object of this study is to identify the combined effect of ANKL and doublet chemotherapy in advanced NSCLC. The investigators design the combination of ANKL and approved chemotherapy as the 3rd and 4th courses in the patients who get stable response after x2 induction as the first line chemotherapy. ANKL (2x10\*9) from peripheral blood 32ml is administered rapidly iv 12-36hr after each chemotherapeutic agents while peak effect of NK cell ligand modulation by chemotherapeutic agent is maintained. After 4th course, response evaluation is done by Response Evaluation Criteria in Solid Tumors (RECIST) and 40% or more partial response (PR, increased by 15% or more from historical control 25%) is the expected target and Simon's two stage design will be applied through the study (power 80%, a= 0.95, N1= 33, N= 68)

Detailed description: Based on additive or synergistic effect of natural killer (NK) cell and chemotherapy (modulating the expression of NK stimulatory ligand on tumor cell), the investigators performed phase II trial of docetaxel and ANKL combination s the second line treatment in advanced non-small cell lung cancer (NSCLN) and reported the results in May 2013. (Anticancer Research 33;2115, Poster Presentation in ASCO).In that study, the investigators observed the feasibility and safety of ANKL combined with docetaxel in patients with advanced NSCLC, but the clinical benefit was not evaluated properly because the study was interrupted unintentionally and most of the enrolled patients were far advanced with large tumor burden, that is, poor immunological environment for ANKL to work.

The object of this study is to identify the combined effect of ANKL and doublet chemotherapy in advanced NSCLC. The approved doublet chemotherapy based on platinum is widely used with the response rate (RR) 25-35% after 4-6 courses as the first line treatment. The investigators design the combination of ANKL and chemotherapy as the 3rd and 4th courses in the patients who show stable response after x2 courses. Higher RR with the combination treatment is the primary outcome as compared with the chemotherapy alone - historical control; about 12% PR and 50% stable response after x2 initial courses and 25% PR after x2 more courses among the patients who get stable response after x2 initial courses. Peripheral blood 32 ml will be drawn from the patients who decide to be enrolled and about 2 weeks later ANKL (2x10\*9) are scheduled to be administered rapidly iv 12-36hr after each chemotherapeutic agents while peak effect of NK cell ligand modulation by chemotherapeutic agent is maintained. After 4th course, response evaluation is done by RECIST and 40% or more PR (increased by 15% or more from historical control 25%) is the expected target and Simon's two stage design will be applied through the study (power 80%, a= 0.95, N1= 33, N= 68)

Eligibility criteria: Inclusion Criteria:

* advanced NSCLC with measurable lesions,
* age of 20 - 75 years, Eastern Cooperative Oncology Group (ECOG)
* performance status (PS) of 0 to 2, and stable response after x2 induction chemotherapy as first line treatment.
* No major organ dysfunction.

Exclusion Criteria:

* pregnant or lactating woman,
* active hepatitis B or C,
* AIDS or positivity for HIV, autoimmune diseases or treatment with immunosuppressive drugs,
* prior radiotherapy to the target region

Primary outcomes:
measure: response rate
timeFrame: 1 month later after 4th course
Secondary outcomes:
measure: progression free survival
timeFrame: 6 months
Other outcomes:
Locations:
city: Jung-gu
country: Korea, Republic of
facility: Daejeon St. Mary's Hospital
state: Daejeon
Study officials:
affiliation: The Catholic University of Korea
name: Suk Young Park, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Catholic University of Korea
name: Hoon Kim, MD, PhD
role: STUDY_DIRECTOR
References: