Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
This study will determine the safety and efficacy of expanded activated autologous NK cells administered after Trastuzumab in patients with HER2-positive breast or gastric cancer. It will also provide valuable insights of the role of NK cell infusions in adult solid tumors.
Full description
Recently, targeted immunotherapies have become part of the therapeutic arsenal in adult solid tumors, and have shown promising activity in melanomas and prostate cancers. Trastuzumab is a monoclonal antibody that targets HER2 and is used routinely in combination with chemotherapy in HER2 over-expressing breast and gastric cancer. Trastuzumab is known to induce antibody dependent cell cytotoxicity (ADCC), among its various mechanisms for tumor cell kill. As such, trastuzumab may suitably be combined with immunotherapy as a strategy to harness the host's immune system against HER2-positive tumor cells.There is mounting evidence that natural killer (NK) cells have powerful anti-cancer activity. In patients with leukemia undergoing allogeneic hematopoietic stem cell transplant, several studies have demonstrated NK-mediated anti-leukemic activity. Allogeneic NK cell infusions in patients with primary refractory or multiple-relapsed leukemia have been shown to be well tolerated and void of graft-versus-host disease (GVHD) effects. In this study, we seek to enhance the antitumor activity of a commonly used antibody to treat HER2+ breast and gastric cancer, trastuzumab, administered in combination with infusion of activated and expanded autologous NK cells.This is a lead-in phase I followed by a phase II study. Up to 9 patients will be enrolled in phase I to test two different doses of NK cells to be infused into the patient. This will then be followed by a phase II study where 20 patients will be enrolled. Eligible patients will undergo apheresis about 9 days (up to 11 days) prior to cycle 1 therapy to harvest NK cells. The collected NK cells will be expanded and activated ex vivo. On day 1 of cycle 1, the patient will receive herceptin and subcutaneous IL2, followed by NK cell infusion on day 2 of cycle 1. This will then be followed by 5 doses of s/c IL2 three times a week to keep the NK cells activated in vivo. The patient will then receive three more cycles of herceptin (every 21 days). In patients who achieve objective tumor response after cycle 2 or cycle 4, a second NK cell infusion along with s/c IL2 will be administered with cycle 4 or cycle 6 herceptin respectively.This study will determine the safety and efficacy of this novel therapeutic strategy in HER2 positive breast and gastric cancer. It will also provide valuable insights of the role of NK cell infusions in adult solid tumors.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Exclusion criteria
Treatment within the last 30 days with any investigational drug
Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy
Major surgery within 28 days of study drug administration
Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy
Lactating or pregnant.
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:
Second primary malignancy that is clinically detectable at the time of consideration for study enrolment
Symptomatic brain metastases
Receipt of steroids during time period of 3 days prior to expanded NK cell infusion to 30 days after infusion (i.e. day -3 to day +30).
Primary purpose
Allocation
Interventional model
Masking
29 participants in 1 patient group
Loading...
Central trial contact
Soo Chin Lee, MBBS; Joan Phee
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal