Reactivating NK Cells in Treating Refractory Head and Neck Cancer (NKEXPHNC)
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|ClinicalTrials.gov Identifier: NCT02507154|
Recruitment Status : Unknown
Verified August 2018 by National University Hospital, Singapore.
Recruitment status was: Recruiting
First Posted : July 23, 2015
Last Update Posted : August 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Nasopharyngeal Cancer Head and Neck Squamous Cell Carcinoma||Drug: Cetuximab + NK cells||Phase 1 Phase 2|
Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system that are responsible for direct and indirect cytolytic killing of virally-transformed and/or cancer cells. Harnessing NK cells in cancer immunotherapy therefore, provides a direct cytotoxic effect on cancer cells which further stimulates further downstream adaptive anti-tumor immune responses against the cancer. In order to effect a more targeted killing of these tumor cells, using a monoclonal antibody (mAb) to direct these NK cells to the target site is feasible, provided a specific tumor antigen can be identified. In nasopharyngeal Carcinoma (NPC) and head and neck squamous cell carcinoma (HNSCC) where epidermal growth factor receptor (EGFR) is ubiquitously expressed, combining NK cell therapy with cetuximab (a chimeric mouse/human anti-EGFR monoclonal antibody) to direct these NK cells against these EGFR tumor targets is possible. In this study, we seek to enhance the antitumor activity of cetuximab to treat EGFR-positive head and neck cancers by combing infusion of activated expanded autologous NK cells with cetuximab. Patients selected for this trial are those with refractory NPC and HNSCC where no feasible therapeutic options are available. This is a lead-in phase I followed by a phase II study. The phase I study will enroll 9 patients and will test the feasibility and safety of this combination strategy and determine the tolerated dose of NK cell infusion (1x1^06/kg or 1x10^7/kg NK cells) in adult EGFR positive NPC and HNSCC patients. For the first 3 patients, each new patient will only be enrolled at least 3 weeks after treatment of the preceding patient to allow sufficient time to monitor toxicities. Initial phase of treatment consists of 7 weeks of cetuximab monotherapy. At week 8, clinical evaluation will be done to determine patients who are suitable to continue this study with NK cell therapy, based on the severity of toxicities encountered. Eligible patients will undergo apheresis (Day -10) to harvest NK cells. The collected NK cells will be expanded and activated in the laboratory. During cycle 1, cetuximab will be given on day 1 with subcutaneous IL-2 (three times per week for 2 weeks); followed by expanded NK cells on day 2. The purpose of IL-2 is to sustain activity of these NK cells in-vivo. Cetuximab will be administered weekly for additional 2 weeks following the NK cell infusion during cycle 1. For cycle 2 and 3, cetuximab monotherapy will be administered every 21 days. Clinical evaluation will be performed upon completion of cycle 3. Patients with stable disease or with partial response will be allowed to continue with a second NK infusion dose as per cycle 1, followed by additional 2 more cycles of cetuximab monotherapy (every 21 days).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of Expanded, Activated Autologous Natural Killer Cell Infusions With Cetuximab for Patients With EGFR-Positive Nasopharyngeal Carcinoma or Head and Neck Squamous Cell Carcinoma|
|Actual Study Start Date :||July 2015|
|Estimated Primary Completion Date :||August 2019|
|Estimated Study Completion Date :||August 2019|
Experimental: Cetuximab + NK cells
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
Other Name: Erbitux
- Safety as measured by clinical examination including hematology, renal and liver function tests, adverse events and any significant biochemical abnormalities or toxicities [ Time Frame: 12- 18 weeks ]
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).
- Objective tumor response [ Time Frame: Up to 24 months ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02507154
|Contact: Chwee Ming Lim, MBBS||6772 firstname.lastname@example.org|