Solid Tumors
Conditions
Keywords
HER3
Brief summary
The purpose of this study is to assess the PK, safety, and tolerability of patritumab produced by a new manufacturing process (denoted as Process 2 patritumab). The data from this study will allow Process 2 patritumab to be compared to Process 1 patritumab to allow for any dose adjustments, if needed, and to bridge data from studies previously conducted with Process 1 patritumab to studies to be conducted with Process 2 patritumab. The hypothesis for this study is that the pharmacokinetics of Process 2 patritumab will be comparable to those of Process 1 patritumab.
Detailed description
Process 2 patritumab will be administered intravenously as a single, loading dose of 18 mg/kg over approximately 60 minutes at Cycle 1 Day 1 followed by 9 mg/kg administered every 21 days as a maintenance dose starting at Cycle 2 Day 1. This study will be conducted in 2 phases: a main study and an extension phase. The PK profile of Process 2 patritumab will be compared to historical data for Process 1 patritumab. Specifically, the PK parameters (AUC0-21d and Cmax as primary endpoints) for Process 2 patritumab 18 mg/kg (loading dose) will be compared to the PK parameters of Process 1 patritumab 18 mg/kg. Process 2 patritumab serum concentrations will be compared to Process 1 patritumab serum concentrations collected in the Phase 1 and Phase 2 studies by population PK methods and will be reported separately.
Interventions
DRUGpatritumab
Sponsors
Daiichi Sankyo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have a pathologically documented advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available, or for which the subject refuses standard therapy. * Must have a tumor type that is known to express HER3. These tumors include breast, lung, prostate, ovarian, cervical, endometrial, gastric, pancreatic, bladder, head and neck, liver, colon, and esophageal cancer. Other tumors will be considered based on emerging HER3 expression data. * Must be competent and able to comprehend, sign, and date an IRB-approved ICF (including HIPAA authorization, if applicable) before performance of any study-specific procedures or tests. * Must have an ECOG performance status of ≤ 2 * Women must be one of the following: 1. Postmenopausal (having had no menstrual period for a minimum of 12 months) or surgically sterile, or 2. If of childbearing potential, must have been willing to use maximally effective birth control during the period of therapy and use contraception for 6 months following the last investigational drug infusion and must have had a negative urine or serum pregnancy test upon entry into the study. * Men must be surgically sterile or willing to use a double-barrier contraception method upon enrollment, during the course of the study, and for 6 months following the last investigational drug infusion. * Have hematological function, as follows:6. Men * Absolute neutrophil count of ≥ 1.5 × 109/L * Platelet count ≥ 100 × 109/L * Hemoglobin ≥ 9 g/dL * Have renal function, as follows: * Calculated creatinine clearance rate (CrCl) ≥ 60 mL/minute using the modified Cockcroft-Gault equation or serum creatinine ≤ 1.5 × ULN. * Have hepatic function, as follows: * AST ≤ 2.5 × ULN (if liver metastases are present, \< 5 × ULN) * ALT ≤ 2.5 × ULN (if liver metastases are present, \< 5 × ULN) * Alkaline phosphatase ≤ 2.5 × ULN (if bone or liver metastases are present, \< 5 × ULN) * Bilirubin ≤ 1.5 × ULN * Prothrombin time (PT) or partial thromboplastin time (PTT) ≤ 1.5 × ULN
Exclusion criteria
* Have a history of lymphoma, leukemia, or other hematopoietic malignancy. * Have Have autologous or allogeneic stem cell transplant. * Have any comorbid medical condition that would increase the risk of toxicity in the opinion of the investigator or sponsor. * Have untreated or symptomatic brain metastasis. * Have unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE Version 4.0 Grade 0 or 1, or to levels dictated in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC (0-21 day) of Patritumab | 5 Cycles, each of which lasts 21 Days | AUC (0-21 day) of patritumab obtained after a single infusion of Process 2 patritumab 18 mg/kg (loading dose) |
| Cmax of Patritumab | 5 Cycles, each of which lasts 21 Days | Cmax of patritumab obtained after a single infusion of Process 2 patritumab 18 mg/kg (loading dose) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| volume of distribution [Vz] | 5 Cycles, each of which lasts 21 Days | To assess the secondary PK parameters volume of distribution \[Vz\] |
| Safety and Tolerability of Process 2 patritumab - (electrocardiograms [ECG) | 5 Cycles, each of which lasts 21 Days | To assess the safety and tolerability of Process 2 patritumab (electrocardiograms \[ECG) |
| Antibody Formation | 5 Cycles, each of which lasts 21 Days | To characterize the formation of antibodies to patritumab human antihuman antibodies (HAHA) after infusion of Process 2 patritumab |
| Concentration patritumab at 504 hours | 5 Cycles, each of which lasts 21 Days | To assess the secondary PK parameter concentration of patritumab at 504h \[C504\] |
| AUC to infinity [AUC0-inf] | 5 Cycles, each of which lasts 21 Days | To assess the secondary PK parameters AUC to infinity \[AUC0-inf\] |
| clearance (CL) | 5 Cycles, each of which lasts 21 Days | To assess the secondary PK parameters clearance (CL) |
| concentration at the end of infusion (Ceoi) | 5 Cycles, each of which lasts 21 Days | To assess the secondary PK parameters concentration at the end of infusion (Ceoi) |
| terminal elimination half-life (t 1/2) | 5 Cycles, each of which lasts 21 Days | To assess the secondary PK parameters terminal elimination half-life (t 1/2) |
| echocardiograms/multi-gated acquisition [MUGA] scans of Process 2 patritumab | 5 Cycles, each of which lasts 21 Days | To assess the safety and tolerability of Process 2 patritumab echocardiograms/multi-gated acquisition \[MUGA\] scans |
| adverse events [AEs] of Process 2 patritumab | 5 Cycles, each of which lasts 21 Days | To assess the safety and tolerability of Process 2 patritumab adverse events \[AEs\] of Process 2 patritumab |
| time to Cmax (Tmax) | 5 Cycles, each of which lasts 21 Days | To assess the secondary PK parameters time to Cmax (Tmax) |
| trough concentration (Ctrough) | 5 Cycles, each of which lasts 21 Days | To assess the secondary PK parameters trough concentration (Ctrough) |
Countries
United States
Outcome results
None listed