NK Cell Infusions With Trastuzumab for Patients With HER2+ Breast and Gastric Cancer

NCT02030561 | Unknown Phase 1 DMC

• 2 other identifiers: MC01/21/132013/00566
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Breast Cancer; Gastric Cancer

Keywords

NK cells; trastuzumab; immunotherapy

Outcome Measures

Primary Outcomes (3)

• 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

  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.

  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.

  Up to 36 months

Study Arms (1)

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.

Drug: Trastuzumab + NK cells

Interventions

Trastuzumab + NK cells DRUG

Also known as: Herceptin

Trastuzumab + NK cells

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• National University of Singapore: collaborator

Study Sites (2)

National University Hospital

Singapore, Singapore, 119228, Singapore

NOT YET RECRUITING

National University Hospital

Singapore, 119228, Singapore

RECRUITING

Related Publications (2)

• 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.

  PMID: 18485193 BACKGROUND

• Voskens 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.

  PMID: 20937115 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Stomach Neoplasms

Interventions

Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Soo Chin Lee, MBBS

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Soo Chin Lee, MBBS

CONTACT

(65) 6779 5555; Soo_Chin_Lee@nuhs.edu.sg

Joan Phee

CONTACT

(65) 6772 2404; Joan_Phee@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: January 7, 2014
• First Posted: January 8, 2014
• Study Start: January 1, 2014
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2018
• Last Updated: June 22, 2016

Record last verified: 2016-06

Locations

SG (2)