Reactivating NK Cells in Treating Refractory Head and Neck Cancer

NCT02507154 | Unknown Phase 1 DMC

• 1 other identifier: NK0906
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine the safety and efficacy of expanded activated autologous NK cells administered after cetuximab in patients with EGFR-positive nasopharyngeal carcinoma or head and neck squamous cell carcinoma.

Conditions

Nasopharyngeal Cancer; Head and Neck Squamous Cell Carcinoma

Keywords

cetuximab; NK cells; nasopharyngeal cancer; head and neck squamous cell cancer

Outcome Measures

Primary Outcomes (2)

• Safety as measured by clinical examination including hematology, renal and liver function tests, adverse events and any significant biochemical abnormalities or toxicities

  During cycle 1 (21 days) and for at least 21 days following a second NK cell infusion if administered, patients will be reviewed twice a week. Clinical examination including hematology, renal and liver function tests will be performed. Any adverse events (using NCI CTC grading) and concomitant medications notation will be recorded. Any significant biochemical abnormalities or toxicities will be monitored till resolution of these findings or 30 days after patient withdraws from this study, whichever occurs later. During cycles with cetuximab monotherapy, patients with be reviewed once every cycle (21 days).

  12- 18 weeks

• Objective tumor response

  In this study, treatment response will be determined using RECIST 1.1 criteria, after two and four cycles of therapy. The endpoints of the study are objective tumor response including overall response rate (ORR), partial response (PR), duration of complete response (DCR) and duration of partial response (DPR). Complete response is defined by complete resolution of target lesion while partial response is defined by reduction of the target lesion by at least 20% from its baseline. Duration of tumor response will be censored at the date of the last follow-up visit for tumor responders who are still alive and who have not progressed.

  Up to 24 months

Study Arms (1)

Cetuximab + NK cells

EXPERIMENTAL

During cycle 1, patient will receive intravenous cetuximab and subcutaneous IL-2 on day 1, followed by NK cell infusion on day 2, with subcutaneous IL-2 for an additional 5 doses three times a week to support NK cell viability and expansion in vivo. Following NK cell infusion, cetuximab will be administered weekly for another 2 weeks. During cycle 2 and 3, one cycle of cetuximab monotherapy will be administered 3 weeks apart. Patients who demonstrate objective tumor response or stable disease after cycle 3 will receive a second infusion of NK cells along with cetuximab during cycle 4 therapy at the same dose and schedule as in cycle 1. This will be followed by 2 additional cycles of cetuximab monotherapy (3 weeks apart).

Drug: Cetuximab + NK cells

Interventions

Cetuximab + NK cells DRUG

Also known as: Erbitux

Cetuximab + NK cells

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>21
• Histologically confirmed diagnosis of EGFR-positive nasopharyngeal carcinoma or EGFR positive HNSCC (based on \>80% immunohistochemistry of biopsy of recurrent tumor Ventana (Roche) clone 3C6
• Recurrent cancer that is not surgically salvageable
• Metastatic disease (after one course of palliative chemotherapy has been completed)
• Presence of measurable tumor by RECIST 1.1 criteria
• At least two weeks since receipt of any biological therapy, chemotherapy, and/or radiation
• Adequate organ function
• Haemoglobin ≥ 9g/dL ANC ≥ 1500/µL Platelet count ≥ 100,000/µL Creatinine clearance ≥60ml/minute Total bilirubin ≤ 1.5 x upper limit normal (ULN) AST ≤ 5 x upper limit normal ALT ≤ 2 x upper limit normal INR and PTT \<1.5 x upper limit normal (ULN)
• ECOG performance status of 0-2
• Life expectancy of at least 60 days
• Localized radiotherapy for palliative pain management is permissible
• Written consent to participate on study
• Physiological dose of steroid replacement is permissible

You may not qualify if:

• Treatment within the last 30 days with any investigational drug
• Hypersensitivity to cetuximab or any excipients of the NK cell product
• Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy
• Major surgery within 28 days of study drug administration
• Radiotherapy to the target lesions during study or within 3 weeks prior to study treatment.
• Autologous bone marrow transplant
• Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy
• Lactating or pregnant
• Unwilling to use adequate barrier contraception measures during study period.
• Second primary malignancy that is clinically detectable at the time of consideration for study enrolment
• Receipt of immunosuppressives or steroids (=1mg/kg) during time period of 3 days prior to expanded NK cell infusion to 30 days after infusion (i.e. day -3 to day +30).
• Symptomatic brain metastases
• Electrocardiogram with clinically significant findings.
• Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator; serious cardiac illness or medical conditions including but not limited to:
• Patients with dyspnea at rest.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, 119228, Singapore

RECRUITING

Related Publications (1)

• Lim CM, Liou A, Poon M, Koh LP, Tan LK, Loh KS, Petersson BF, Ting E, Campana D, Goh BC, Shimasaki N. Phase I study of expanded natural killer cells in combination with cetuximab for recurrent/metastatic nasopharyngeal carcinoma. Cancer Immunol Immunother. 2022 Sep;71(9):2277-2286. doi: 10.1007/s00262-022-03158-9. Epub 2022 Jan 30.

  PMID: 35098345 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Chwee Ming Lim, MBBS

CONTACT

6772 2631; chwee_ming_lim@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2015
• First Posted: July 23, 2015
• Study Start: July 1, 2015
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: August 21, 2018

Record last verified: 2018-08

Locations

SG (1)