Carcinoma, Lymphoma, Sarcoma
Conditions
Brief summary
2.1 Primary Objectives 1. To measure the human dosimetry of 64Cu-DOTA-U3-1287 in subjects with advanced solid tumors (Cohort 1 only) 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. To determine the safety and tolerability of 64Cu-DOTA-U3-1287 (all cohorts) 2.2 Secondary Objectives 1. To determine the relationship between U3-1287 serum concentration and HER3 receptor occupancy (as measured by PET/CT) in subjects with advanced solid tumors 2. 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) 3. To characterize the PK exposure of U3 1287 when administered intravenously to patients with advanced solid malignancies. 4. To measure the rate of anti-U3-1287 human antibody development in subjects with advanced solid tumors treated with U3 1287 monotherapy 2.3 Exploratory Objectives 1. To assess tumor volume changes after U3-1287 treatment by CT or magnetic resonance imaging (MRI) (Part 2 only) 2. To assess blood, body fluid/tissue, and tumor specimens for potential biomarkers (e.g., proteins and transcripts) that predict response to U3-1287 3. 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
Interventions
DRUG64Cu-DOTA-U3-1287
DRUGU3-1287 (unlabeled)
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 * Patient must have an LVEF of ≥ 50% * Patient must be ≥ 18 years old * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 6 months following the completion of study treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Patient must be willing and able to undergo the imaging studies outlined in the protocol (in the opinion of the investigator) * Patient must be able to understand and willing to sign an institutional review board (IRB) approved informed consent form * Patient must have archival tissue available for HER3 expression analysis
Exclusion criteria
* 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 any unresolved toxicities \> grade 1 with the exception of grade 2 lymphopenia and/or alopecia from prior anti-cancer therapy Note: Grade 2 or 3 toxicities from prior therapy that are considered irreversible (defined as having been present and stable for \> 3 months), such as ifosfamide-related proteinuria, or treatment related neuropathy, may be allowed if they are not otherwise described in the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Human dosimetry of 64Cu-DOTA-U3-1287 in subjects with advanced solid tumors (Cohort 1 only) | 2 days | Measurement of the human dosimetry at 3 hours post dose, 24 hours post dose and 48 hours post dose. |
| 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)) | 9 days | 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 |
| Safety and tolerability of 64Cu-DOTA-U3-1287 (all cohorts) | From first receiving study treatment until the 8-week follow-up after the conclusion of treatment or death | Based on adverse events according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relationship between U3-1287 serum concentration and HER3 receptor occupancy in subjects with advanced solid tumors | 9 days | Measured by PET/CT at 24 hours post dose Day 1 and 24 hours post dose Day 8 |
| 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 | Defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1. Screening, after two dose (6 weeks) of U3-1287 during Part 2, and every 9 weeks thereafter. |
| PK exposure of U3-1287 when administered intravenously to patients with advanced solid malignancies. | Various timepoints depending on cohort | Cohort 1 Part 1 = Day 1 predose, end of infusion, hour 3, 24 hours, 48 hours, and 72 hours. Cohort 1 Part 2 = Day 8 predose, 5 minutes pre-end of infusion, hour 6, day 9, day 15, day 22, and then every 3 weeks. Cohorts 2-5 Part 1 = Day 1 predose, end of infusion, 24 hours, Day 8 predose, end of infusion, and Day 9. Cohorts 2-5 Part 2 = Day 29 predose, end of infusion, Day 30, and every 3 weeks. |
| 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 | Pre-infusion on Day 1 of every cycle and end of study treatment visit. For patients positive for anti-U3-1287 neutralizing antibody on the serum sample drawn at the final visit, additional serum samples should be obtained until the level returns to baseline (or becomes negative) or up to 1 year from the last dose of study drug or if the patient starts another therapy for his/her cancer, whichever occurs first. |
Countries
United States
Outcome results
None listed