Breast CancerPhase 1/2NCT02030561
NK Cell Infusions With Trastuzumab for Patients With HER2+ Breast and Gastric Cancer
A Phase 1/2 study testing Trastuzumab + NK cells in people with Breast Cancer and Gastric Cancer, run by National University Hospital, Singapore at 2 sites in Singapore.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- Breast Cancer, Gastric Cancer
- What is being tested?
- Trastuzumab + NK cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesSingapore
- Study dates
- Jan 2014to Aug 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-65
- Histologically confirmed diagnosis of HER2-positive breast or gastric cancer (defined as IHC 3+ or HER2 FISH amplification ratio >2.2)
- Metastatic disease
- Presence of measurable tumour by RECIST 1.1 criteria
- Must have failed at least two lines of trastuzumab-containing systemic therapy (documented relapse while receiving adjuvant or neoadjuvant trastuzumab for HER2 positive breast cancer is eligible)
- At least two weeks since receipt of any biological therapy, chemotherapy, and/or radiation therapy
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- Left ventricular ejection fraction ≥50%
- Adequate organ function ANC ≥ 1500/µL Platelet count ≥ 100,000/µL Creatinine clearance ≥60ml/minute Total bilirubin ≤ 1.5 x upper limit normal (ULN) AST ≤ 2 x upper limit normal ALT ≤ 2 x upper limit normal
- ECOG performance status of 0-1
- Life expectancy of at least 60 days
- Negative serum or urine pregnancy test result within 14 days prior to enrolment for women who are of childbearing potential
- Ability to provide informed consent. Otherwise, a legally authorized representative (LAR) must be present throughout the consent process and is allowed to give consent on the patient's behalf.
- Patients with reproductive potential must agree to use an approved contraceptive method
- Ability to comply with study procedures
Who cannot join
- 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:
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- Patients with dyspnea at rest.
- History of documented congestive heart failure
- High risk uncontrolled arrhythmias
- Angina pectoris requiring a medicinal product
- Clinically significant valvular disease
- Evidence of transmural infarction on ECG
- Poorly controlled hypertension
- 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).
Trial locations and contacts
2 sites in 1 country.
Singapore2 sites, 2 recruiting
- Not yet recruiting
National University Hospital
Singapore, Singapore, 119228
Soo Chin Lee, MBBS, (65) 6779 5555, Soo_Chin_Lee@nuhs.edu.sg
Soo Chin Lee, MBBS
- Recruiting
National University Hospital
Singapore, 119228
Soo Chin Lee, MBBS, +65 6779 5555, Soo_Chin_Lee@nuhs.edu.sg
Dario Campana, MBBS
About this study
Official title: Phase I/II Study of Expanded, Activated Autologous Natural Killer Cell Infusions With Trastuzumab for Patients With HER2+ Breast and Gastric Cancer
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.
Read the detailed 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.
- Conditions
- Breast Cancer, Gastric Cancer
- Being tested
- Trastuzumab + NK cells
- Keywords
- NK cells, trastuzumab, immunotherapy
- Medical subject headings
- Breast Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab + NK cellsDrug
Also called Herceptin
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab + NK cells | Experimental | During cycle 1, Day 1 patient will receive intravenous trastuzumab and subcutaneous IL-2 on day 1, followed by NK cell infusion on day 2, followed by subcutaneous IL-2 for an additional 5 doses three times a week to support NK cell viability and expansion in vivo.
From cycles 2-4, patient will receive trastuzumab monotherapy alone every 21 days, except for patients who achieve objective tumor response after 2 cycles of therapy, who will then receive an additional infusion of NK cells along with trastuzumab during cycle 4 therapy at the same dose and schedule as in cycle 1.
Patients will be taken off study after cycle 4, unless the patient has objective tumor response after 4 cycles of therapy with only stable disease after cycle 2, in which case the patient will be given another 2 cycles of trastuzumab with an additional NK cell infusion during cycle 6 therapy at the same dose and schedule as in cycle 1. Receives: Drug: Trastuzumab + NK cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Serious and Non-Serious Adverse Events
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 with
- Limited physical examination to include blood pressure, heart rate, weight
- Full blood count, renal function and liver function tests
- Toxicity rating using the NCI CTC scale
- Concomitant medication notation and number of units required for transfusions
Any significant abnormalities or significant toxicities have to be followed until recovery to baseline or 30 days after patient withdraws from the study, whichever occurs later.
During other cycles when only trastuzumab is administered (without NK cells infusion or IL-2) Patients will be reviewed once every cycle of every 3-weekly cycle
Measured: Up to 12-18 weeks
Duration of Tumor Response Measure
Among tumor responders, the duration of tumor response is measured from the date of enrolment until the first date of documented disease progression or death due to any cause, whichever occurs first. 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.
Measured: Up to 36 months
Time-to-Event Outcome Measure
Time to documented disease progression is defined as the time from the date of enrolment to the first date of documented disease progression. Time to documented disease progression will be censored at the date of death for patients who have not had documented disease progression. For patients who are still alive at the time of analysis and who have not had documented disease progression, time to documented disease progression will be censored at the date of the last follow-up visit.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionAug 2017 (estimated)
- Study completionAug 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- National University of Singapore
- Responsible party
- Sponsor
- Investigators
- Soo Chin Lee, MBBS, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02030561
- Sponsor's protocol ID
- MC01/21/13
- Other IDs
- 2013/00566
- Status last verified
- Jun 2016
- First submitted
- 7 Jan 2014
- Last updated
- 22 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Beano A, Signorino E, Evangelista A, Brusa D, Mistrangelo M, Polimeni MA, Spadi R, Donadio M, Ciuffreda L, Matera L. Correlation between NK function and response to trastuzumab in metastatic breast cancer patients. J Transl Med. 2008 May 16;6:25. doi: 10.1186/1479-5876-6-25.
PubMed 18485193Voskens CJ, Watanabe R, Rollins S, Campana D, Hasumi K, Mann DL. Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity. J Exp Clin Cancer Res. 2010 Oct 11;29(1):134. doi: 10.1186/1756-9966-29-134.
PubMed 20937115
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Expanded, Activated Autologous Natural Killer Cell Infusions With Trastuzumab for Patients With HER2+ Breast and Gastric Cancer
- ClinicalTrials.gov ID
- NCT02030561
- Acronym / sponsor ID
- MC01/21/13
- Conditions
- Breast Cancer, Gastric Cancer
- Keywords
- NK cells, trastuzumab, immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- National University of Singapore
- Study start
- Jan 2014
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Aug 2018 (estimated)
- First posted
- 8 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab + NK cells | Experimental | Drug: Trastuzumab + NK cellsDuring cycle 1, Day 1 patient will receive intravenous trastuzumab and subcutaneous IL-2 on day 1, followed by NK cell infusion on day 2, followed by subcutaneous IL-2 for an additional 5 doses three times a week to support NK cell viability and expansion in vivo. From cycles 2-4, patient will receive trastuzumab monotherapy alone every 21 days, except for patients who achieve objective tumor response after 2 cycles of therapy, who will then receive an additional infusion of NK cells along with trastuzumab during cycle 4 therapy at the same dose and schedule as in cycle 1. Patients will be taken off study after cycle 4, unless the patient has objective tumor response after 4 cycles of therapy with only stable disease after cycle 2, in which case the patient will be given another 2 cycles of trastuzumab with an additional NK cell infusion during cycle 6 therapy at the same dose and schedule as in cycle 1. |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age 18-65
- Histologically confirmed diagnosis of HER2-positive breast or gastric cancer (defined as IHC 3+ or HER2 FISH amplification ratio >2.2)
- Metastatic disease
- Presence of measurable tumour by RECIST 1.1 criteria
- Must have failed at least two lines of trastuzumab-containing systemic therapy (documented relapse while receiving adjuvant or neoadjuvant trastuzumab for HER2 positive breast cancer is eligible)
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trastuzumab + NK cellsAlso: Herceptin | Drug | Trastuzumab + NK cells |
Primary outcome
Number of Participants with Serious and Non-Serious Adverse Events
Time frame: Up to 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 with * Limited physical examination to include blood pressure, heart rate, weight * Full blood count, renal function and liver function tests * Toxicity rating using the NCI CTC scale * Concomitant medication notation and number of units required for transfusions Any significant abnormalities or significant toxicities have to be followed until recovery to baseline or 30 days after patient withdraws from the study, whichever occurs later. During other cycles when only trastuzumab is administered (without NK cells infusion or IL-2) Patients will be reviewed once every cycle of every 3-weekly cycle
Duration of Tumor Response Measure
Time frame: Up to 36 months
Among tumor responders, the duration of tumor response is measured from the date of enrolment until the first date of documented disease progression or death due to any cause, whichever occurs first. 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.
Time-to-Event Outcome Measure
Time frame: Up to 36 months
Time to documented disease progression is defined as the time from the date of enrolment to the first date of documented disease progression. Time to documented disease progression will be censored at the date of death for patients who have not had documented disease progression. For patients who are still alive at the time of analysis and who have not had documented disease progression, time to documented disease progression will be censored at the date of the last follow-up visit.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2016.
- Background: PubMed 18485193Beano A, Signorino E, Evangelista A, Brusa D, Mistrangelo M, Polimeni MA, Spadi R, Donadio M, Ciuffreda L, Matera L. Correlation between NK function and response to trastuzumab in metastatic breast cancer patients. J Transl Med. 2008 May 16;6:25. doi: 10.1186/1479-5876-6-25.
- Background: PubMed 20937115Voskens CJ, Watanabe R, Rollins S, Campana D, Hasumi K, Mann DL. Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity. J Exp Clin Cancer Res. 2010 Oct 11;29(1):134. doi: 10.1186/1756-9966-29-134.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Soo Chin Lee, MBBS principal investigator
National University Hospital, Singapore
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Trastuzumab + NK cells in people with Breast Cancer and Gastric Cancer, run by National University Hospital, Singapore at 2 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Soo Chin Lee, MBBS ((65) 6779 5555, Soo_Chin_Lee@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Serious and Non-Serious Adverse Events (time frame: Up to 12-18 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02030561, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2016.