Evaluation of 64Cu-DOTA-U3-1287 in Subjects With Advanced Solid Tumors

NCT01479023 | Terminated Phase 1

• 1 other identifier: 201202074
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

2.1 Primary Objectives

1. 1.To measure the human dosimetry of 64Cu-DOTA-U3-1287 in subjects with advanced solid tumors (Cohort 1 only)
2. 2.To calculate HER3 receptor occupancy (via quantification of the tumor-localized PET signal produced by 64Cu-DOTA-U3-1287 in the absence and presence of competing unlabeled U3-1287 in subjects with advanced solid tumors (Cohorts 2 through 5))
3. 3.To determine the safety and tolerability of 64Cu-DOTA-U3-1287 (all cohorts)
4. 4.To determine the relationship between U3-1287 serum concentration and HER3 receptor occupancy (as measured by PET/CT) in subjects with advanced solid tumors
5. 5.To measure the tumor response rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in subjects with advanced solid tumors treated with U3-1287 (Part 2 only)
6. 6.To characterize the PK exposure of U3 1287 when administered intravenously to patients with advanced solid malignancies.
7. 7.To measure the rate of anti-U3-1287 human antibody development in subjects with advanced solid tumors treated with U3 1287 monotherapy
8. 8.To assess tumor volume changes after U3-1287 treatment by CT or magnetic resonance imaging (MRI) (Part 2 only)
9. 9.To assess blood, body fluid/tissue, and tumor specimens for potential biomarkers (e.g., proteins and transcripts) that predict response to U3-1287
10. 10.To obtain tumor samples for DNA extraction for analysis of potential predictors of response to U3-1287 and any related genes as suggested by emerging data

Conditions

Carcinoma; Sarcoma; Lymphoma

Outcome Measures

Primary Outcomes (3)

• Human dosimetry of 64Cu-DOTA-U3-1287 in subjects with advanced solid tumors (Cohort 1 only)

  Measurement of the human dosimetry at 3 hours post dose, 24 hours post dose and 48 hours post dose.

  2 days

• HER3 receptor occupancy (via quantification of the tumor-localized PET signal produced by 64Cu-DOTA-U3-1287 in the absence and presence of competing unlabeled U3-1287 in subjects with advanced solid tumors (Cohorts 2 through 5))

  Calculation of HER3 receptor occupancy (via quantification of the tumor-localized PET signal produced by 64Cu-DOTA-U3-1287 in the absence and presence of competing unlabeled U3-1287

  9 days

• Safety and tolerability of 64Cu-DOTA-U3-1287 (all cohorts)

  Based on adverse events according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  From first receiving study treatment until the 8-week follow-up after the conclusion of treatment or death

Secondary Outcomes (4)

• Relationship between U3-1287 serum concentration and HER3 receptor occupancy in subjects with advanced solid tumors

  9 days

• Tumor response rate in subjects with advanced solid tumors treated with U3-1287 (Part 2 only)

  Followed for 8 weeks following last administration of study or until death, whichever occurs first

• PK exposure of U3-1287 when administered intravenously to patients with advanced solid malignancies.

  Various timepoints depending on cohort

• Rate of anti-U3-1287 human antibody development in subjects with advanced solid tumors treated with U3-1287 monotherapy

  Up to 1 year from the last dose of study drug

Study Arms (7)

Cohort 1

EXPERIMENTAL

64Cu-DOTA-U3-1287 at a radiotracer dosage of 8-15 mCI and ≤ 0.2 mg of DOTA-U3-1287 on Day 1. Patient will have option to continue to Part 2 (extension phase).

Drug: 64Cu-DOTA-U3-1287; Drug: U3-1287 (unlabeled)

Cohort 2

EXPERIMENTAL

64Cu-DOTA-U3-1287 at the radiotracer dosage defined by Cohort 1 and ≤ 0.2 mg of DOTA-U3-1287 on Day 1. 9.0 mg/kg unlabeled U3-1287 followed by a second dose of ≤ 0.2 mg 64Cu-DOTA-U3-1287 on Day 8. Patient will have option to continue to Part 2 (extension phase).

Drug: 64Cu-DOTA-U3-1287; Drug: U3-1287 (unlabeled)

Cohort 3

EXPERIMENTAL

64Cu-DOTA-U3-1287 at the radiotracer dosage defined by Cohort 1 and ≤ 0.2 mg of DOTA-U3-1287 on Day 1. 12.0 mg/kg unlabeled U3-1287 followed by a second dose of ≤ 0.2 mg 64Cu-DOTA-U3-1287 on Day 8. Patient will have option to continue to Part 2 (extension phase).

Drug: 64Cu-DOTA-U3-1287; Drug: U3-1287 (unlabeled)

Cohort 3a

EXPERIMENTAL

64Cu-DOTA-U3-1287 at the radiotracer dosage defined by Cohort 1 and ≤ 0.2 mg of DOTA-U3-1287 on Day 1. 15.0 mg/kg unlabeled U3-1287 followed by a second dose of ≤ 0.2 mg 64Cu-DOTA-U3-1287 on Day 8. Patient will have option to continue to Part 2 (extension phase).

Drug: 64Cu-DOTA-U3-1287; Drug: U3-1287 (unlabeled)

Cohort 4

EXPERIMENTAL

64Cu-DOTA-U3-1287 at the radiotracer dosage defined by Cohort 1 and ≤ 0.2 mg of DOTA-U3-1287 on Day 1. 18.0 mg/kg unlabeled U3-1287 followed by a second dose of ≤ 0.2 mg 64Cu-DOTA-U3-1287 on Day 8. Patient will have option to continue to Part 2 (extension phase).

Drug: 64Cu-DOTA-U3-1287; Drug: U3-1287 (unlabeled)

Cohort 5

EXPERIMENTAL

64Cu-DOTA-U3-1287 at the radiotracer dosage defined by Cohort 1 and ≤ 0.2 mg of DOTA-U3-1287 on Day 1. TBD (to be determined) mg/kg unlabeled U3-1287 followed by a second dose of ≤ 0.2 mg 64Cu-DOTA-U3-1287 on Day 8. Patient will have option to continue to Part 2 (extension phase).

Drug: 64Cu-DOTA-U3-1287; Drug: U3-1287 (unlabeled)

Part 2 (extension phase)

EXPERIMENTAL

Loading dose of 18.0 mg/kg unlabeled U3-1287 followed by 9.0 mg/kg unlabeled U3-1287 every 3 weeks.

Drug: 64Cu-DOTA-U3-1287; Drug: U3-1287 (unlabeled)

Interventions

64Cu-DOTA-U3-1287 DRUG

Cohort 1; Cohort 2; Cohort 3; Cohort 3a; Cohort 4; Cohort 5; Part 2 (extension phase)

U3-1287 (unlabeled) DRUG

Cohort 1; Cohort 2; Cohort 3; Cohort 3a; Cohort 4; Cohort 5; Part 2 (extension phase)

Eligibility Criteria

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

You may qualify if:

• Patient must have measurable disease as defined by RECIST 1.1, with the additional requirement of at least one lesion ≥ 1.5 cm on CT scan or detectable on FDG-PET performed within 30 days prior to screening
• Patient must have a tumor where HER3 expression is expected (this includes breast, colon, lung, prostate, ovarian, cervical, endometrial, gastric, pancreatic, bladder, head and neck, liver, and esophageal cancer, but other tumors will be considered based on emerging HER3 expression data)
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Patient must have pathologically documented, definitively diagnosed, advanced solid tumors that are refractory to standard treatment or for which no curative therapy is available
• Patient must have adequate hematologic and organ function as follows:
• Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL
• Serum creatinine ≤ 2 x IULN
• AST ≤ 2.5 x IULN (≤ 5.0 x IULN if attributable to liver metastasis)
• ALT ≤ 2.5 x IULN (≤ 5.0 x IULN if attributable to liver metastasis)
• Alkaline phosphatase ≤ 2.0 x ULN (if bone or liver metastases are present, \< 5 x ULN)
• Total bilirubin ≤ 1.5 IULN
• Amylase or lipase ≤ 2.0 x IULN
• Prothrombin time (PT) or partial thromboplastin time (PTT) ≤ 1.5 x IULN

You may not qualify if:

• Patient must not have the liver and/or spleen as the only site(s) of disease (as PET/CT imaging of 64Cu-DOTA-U3-1287 may be difficult in these anatomic locations)
• Patient must not have untreated or symptomatic primary central nervous system metastases or symptoms of brain metastases; any stereotactic radiation or whole brain radiation therapy must have been completed at least 4 weeks prior to study entry
• Patient must not have ascites or pleural effusion requiring medical intervention
• Patient must not have had a myocardial infarction within 6 months of Day 1 or any unstable or uncontrolled disease/condition related to or impacting cardiac function (i.e., unstable angina, congestive heart failure, New York Heart Association \> class II, uncontrolled hypertension \[diastolic \> 95 mmHg; systolic \>140 mmHg\])
• Patient not have cardiac arrhythmia or clinically significant ECG abnormalities
• Patient must not be known to be positive for human immunodeficiency virus (HIV) infection, hepatitis C virus, or chronic active hepatitis B infection
• Patient must not have a known sensitivity to any components of the formulation
• Patient must not be receiving any concomitant antitumor treatment or chemotherapy, radiotherapy, and hormonal therapy (with the exception of Lupron for prostate cancer and SERMS for breast cancer subjects) within 4 weeks of Day 1 (6 weeks for nitrosoureas or mitomycin and 2 weeks for small molecule tyrosine kinase inhibitors)
• Patient must not be receiving any concomitant immunosuppressant therapy (cyclosporine A, FK506, etc., or chronic \> 5 mg/d of prednisone)
• Patient must not be receiving any other concomitant investigational procedures and must not have participated in any other clinical trial with an investigational device or agent within 4 weeks of the first dose of 64Cu-DOTA-U3-1287
• Patient must not have had any previous exposure to U3-1287
• Patient must not have had any previous treatment with HER3 antagonists
• Patient must not have had G-CSF support therapy within 2 weeks of Day 1
• Patient must not have received red blood cell (RBC) transfusion within 2 weeks of Day 1
• Patient must not have received platelet transfusion within 2 weeks of Day 1

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Lockhart AC, Liu Y, Dehdashti F, Laforest R, Picus J, Frye J, Trull L, Belanger S, Desai M, Mahmood S, Mendell J, Welch MJ, Siegel BA. Phase 1 Evaluation of [(64)Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors. Mol Imaging Biol. 2016 Jun;18(3):446-53. doi: 10.1007/s11307-015-0912-y.

  PMID: 26567113 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma; Sarcoma; Lymphoma

Interventions

patritumab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective and Soft Tissue; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• A. Craig Lockhart, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2011
• First Posted: November 24, 2011
• Study Start: April 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: March 1, 2013
• Last Updated: December 20, 2013

Record last verified: 2013-12

Locations

US (1)