NCT01413451

Brief Summary

Background: \- Amatuximab is a cancer treatment drug that targets mesothelin. High levels of this substance are found on some kinds of tumor cells. Lab studies have shown that amatuximab helps the immune system to kill cells that have high levels of mesothelin. However, more research is needed to determine how safe and effective amatuximab is for treating tumors with high levels of mesothelin. Objectives: \- To assess the safety and effectiveness of amatuximab in treating tumors with high levels of mesothelin. Eligibility: \- Individuals at least 18 years of age who have a type of cancer that overexpresses mesothelin. Design:

  • Participants will be screened with a medical history and physical exam. They will also have blood tests and tumor assessment studies.
  • Participants will have two intravenous doses of amatuximab several hours apart. Researchers will monitor them closely and do frequent blood draws. On the same day and also within 48 hours of the second dose, participants will have imaging studies. These studies will measure how well the amatuximab is working against the cancer.
  • Participants will have a third imaging study of the cancer about 1 week after the infusions.
  • Participants will have a followup visit 2 weeks after receiving amatuximab. This visit will require blood samples. Four weeks after receiving the drug, researchers will review patients symptoms or side effects. This interview can be done in person or by phone.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
7

participants targeted

Target at below P25 for early_phase_1

Timeline
Completed

Started Jul 2011

Typical duration for early_phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 12, 2011

Completed
28 days until next milestone

First Submitted

Initial submission to the registry

August 9, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 10, 2011

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 15, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 15, 2013

Completed
Last Updated

December 17, 2019

Status Verified

November 15, 2013

Enrollment Period

2.3 years

First QC Date

August 9, 2011

Last Update Submit

December 14, 2019

Conditions

Carcinoma, Pancreatic DuctalMesotheliomaOvarian NeoplasmsCarcinoma, Non-Small-Cell Lung

Keywords

Monoclonal IgG AntibodyBiodistributionPharmacokineticsHACASafetyMesotheliomaOvarian CancerPancreatic Duct CancerNon-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

  • Biodistribution of radiolabelled amatuximab in tumor and nontumor tissues.

  • Tumor

  • Background ratio of maximum counts

Secondary Outcomes (4)

  • CTCAE V.4 events

  • Observation of HACA

  • PKs

  • Antibody uptake vs. IHC mesothelin expression

Interventions

Amatuximab (MORab-009)DRUG

Eligibility Criteria

Age18 Years - 100 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Female or male subjects, greater than or equal to 18 years of age.
  • Histologically-confirmed diagnosis of pancreatic adenocarcinoma, mesothelioma, mesothelin-positive ovarian cancer, or NSCLC. A new biopsy is not required; the diagnostic biopsy sample will be sufficient. IHC confirmation of mesothelin-positivity is not necessary for pancreatic adenocarcinoma and mesothelioma as nearly 100% of pancreatic adenocarcinomas and mesotheliomas express mesothelin. Mesothelin expression in ovarian cancer and NSCLC will be tested by IHC and any degree of positivity (1+, 2+, or 3+) will be accepted.
  • Subjects are required to have measurable disease that has progressed through prior therapy and that includes a non-hepatic lesion for imaging that is greater than or equal to 1.5 cm, as defined by Modified Response Evaluation Criteria in Solid Tumors (RECIST).
  • Eastern Cooperative Oncology Group (ECOG) performance status or 0, 1, or 2.
  • Female subjects of childbearing potential and all male subjects are required to consent to use a medically acceptable method of contraception throughout the study period and for 30 days after amatuximab administration. A barrier method of contraception is required.
  • Laboratory and clinical results within the 2 weeks prior to Day of Infusion as follows:
  • Absolute neutrophil count (ANC): greater than or equal to 1.5 times 10(9)/L
  • Platelet count: greater than or equal to 75 times 10(9)/L
  • Hemoglobin: greater than or equal to 9 g/dL
  • Serum bilirubin: less than or equal to 1.5 mg/dL
  • Aspartate transaminase (AST): less than or equal to 3 x upper limit of normal (ULN) (less than or equal to 5 ULN acceptable for pancreatic patients with known liver metastasis only)
  • Alanine transaminase (ALT) less than or equal to 3 times upper limit of normal (ULN) (less than or equal to 5 ULN acceptable for pancreatic patients with known liver metastasis only)
  • Alkaline Phosphatase less than or equal to 5 times ULN
  • Serum creatinine less than or equal to 1.5 mg/dL
  • Subjects are required to be willing and able to provide written informed consent.

You may not qualify if:

  • Subjects are ineligible to participate in this study if any of the following criteria are met:
  • Known allergy or hypersensitivity to monoclonal antibodies;
  • Prior treatment with amatuximab;
  • Prior treatment with SS1(dsFv)PE38 (SS1P);
  • Known brain metastases;
  • Known prosthetic devices that would prohibit imaging of lesion of interest due to radiographic artifact;
  • Evidence of other active malignancy requiring treatment;
  • Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class III or IV, angina not well controlled by medication, or myocardial infarction within 6 months);
  • ECG demonstrating clinically significant arrhythmias. Subjects with chronic atrial arrhythmia, (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia), are eligible;
  • Active serious systemic disease, including active bacterial or fungal infection within 2 weeks before study entry;
  • Active viral hepatitis or symptomatic human immunodeficiency virus (HIV) infection;
  • Treatment within 3 months with immunomodulatory therapy (e.g., interferons, immunoglobulin therapy, Interleukin 1 receptor antagonist (IL-1RA) or systemic corticosteroids). Short-term systemic corticosteroids or topical or intra-articular steroids are acceptable, at the discretion of the Investigator;
  • Chemotherapy, biologic therapy, radiation therapy or immunotherapy within 3 weeks prior to dosing with amatuximab;
  • Breast-feeding, pregnant, or likely to become pregnant during the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

  • Hassan R, Ebel W, Routhier EL, Patel R, Kline JB, Zhang J, Chao Q, Jacob S, Turchin H, Gibbs L, Phillips MD, Mudali S, Iacobuzio-Donahue C, Jaffee EM, Moreno M, Pastan I, Sass PM, Nicolaides NC, Grasso L. Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin. Cancer Immun. 2007 Dec 19;7:20.

    PMID: 18088084BACKGROUND

  • Hassan R, Ho M. Mesothelin targeted cancer immunotherapy. Eur J Cancer. 2008 Jan;44(1):46-53. doi: 10.1016/j.ejca.2007.08.028. Epub 2007 Oct 22.

    PMID: 17945478BACKGROUND

  • Gubbels JA, Belisle J, Onda M, Rancourt C, Migneault M, Ho M, Bera TK, Connor J, Sathyanarayana BK, Lee B, Pastan I, Patankar MS. Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors. Mol Cancer. 2006 Oct 26;5(1):50. doi: 10.1186/1476-4598-5-50.

    PMID: 17067392BACKGROUND

MeSH Terms

Conditions

Carcinoma, Pancreatic DuctalMesotheliomaOvarian NeoplasmsCarcinoma, Non-Small-Cell Lung

Interventions

amatuximab

Condition Hierarchy (Ancestors)

Carcinoma, DuctalAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms, Ductal, Lobular, and MedullaryPancreatic NeoplasmsDigestive System NeoplasmsNeoplasms by SiteEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System DiseasesAdenomaNeoplasms, MesothelialOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesGonadal DisordersCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Raffit Hassan, M.D.

    National Cancer Institute (NCI)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH

Study Record Dates

First Submitted

August 9, 2011

First Posted

August 10, 2011

Study Start

July 12, 2011

Primary Completion

November 15, 2013

Study Completion

November 15, 2013

Last Updated

December 17, 2019

Record last verified: 2013-11-15

Locations

US(1)