Combined Effect of Natural Killer Cell and Doublet Chemotherapy in Advanced NSCLC as the 1st Line Treatment (ANKL-2)

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

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)

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Biological: ANKL(Ex vivo-expanded NK cell enriched lymphocytes)

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)

• Study Type: Interventional
• Enrollment (Anticipated): 68
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bo Ra Hong, RN; Phone Number: +82-10-6402-9535; Email: shbrp@hanmail.net
• Study Contact Backup: Name: Young Jun Yang, MD; Phone Number: +82-10-6435-7009; Email: yyj7009@hanmail.net

Study Locations

• Korea, Republic of
  • Daejeon
    • Jung-gu, Daejeon, Korea, Republic of, 34943
      • Recruiting
      • Daejeon St. Mary's hospital
      • Contact: Suk Young Park, MD, PhD; Phone Number: 82-42-220-9821; Email: sypark1011@hotmail.com
      • Contact: young Jun Yang, MD; Phone Number: 82-10-6435-7009; Email: yyj7009@daum.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ANKL combined with chemotherapy; combination of ANKL and doublet chemotherapy as 3rd and 4th course in patients who get stable response after initial x2 courses	Biological: ANKL(Ex vivo-expanded NK cell enriched lymphocytes); add ANKL in 3rd and 4th course in case of stable response after two initial courses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
response rate	confirmed response rate by CT scan	1 month later after 4th course

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival	CT or other imaging modality	6 months

Collaborators and Investigators

• Sponsor: The Catholic University of Korea
• Investigators: Principal Investigator: Suk Young Park, MD, PhD, The Catholic University of Korea; Study Director: Hoon Kim, MD, PhD, The Catholic University of Korea

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): February 1, 2020

Study Registration Dates

• First Submitted: February 1, 2015
• First Submitted That Met QC Criteria: February 23, 2015
• First Posted (Estimate): February 24, 2015

Study Record Updates

• Last Update Posted (Estimate): February 3, 2017
• Last Update Submitted That Met QC Criteria: February 1, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Autologous Ex vivo-expanded NK cell enriched lymphocytes
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: CUMC-ANKL-002