Adnexal Diseases, Digestive System Diseases, Digestive System Neoplasms, Ovarian Diseases, Ovarian Neoplasms, Pancreatic Diseases, Pancreatic Neoplasms
Conditions
Keywords
Pancreatic cancer, Ovarian cancer
Brief summary
The purpose of this multicenter imaging sub study is to evaluate the biodistribution and organ pharmacokinetics of 89Zr-MMOT0530A in patients with unresectable pancreatic or platinum-resistant ovarian cancer. MMOT0530A is a monoclonal antibody that targets an antigen overexpressed in pancreatic and ovarian cancer. Subsequent to imaging with 89Zr-MMOT0530A, patients will be treated with DMOT4039A in the DMO4993g protocol (clinicaltrials.gov identifier NCT01469793) after this study. DMOT4039A is an antibody-drug conjugate composed of the monoclonal antibody MMOT0530A and the mitotic agent monomethyl auristatin (MMAE). By imaging patients with the monoclonal antibody MMOT0530A before treatment, the correlation between tumor uptake of 89Zr-MMOT0530A and response to DMOT4039A therapy will be assessed.
Detailed description
A challenge in current drug development using molecular targeted therapies is the high level of heterogeneity that is present in specific tumor types. The ability to safely and accurately predict the presence or absence of the target is essential for the therapeutic effect of the newly developed drugs. DMOT0439A is one of those novel designed molecular targeted drugs; an antibody-drug conjugate composed of the monoclonal antibody MMOT0530A and the mitotic agent monomethyl auristatin (MMAE). In the DMO4993g protocol (clinicaltrials.gov identifier NCT01469793), the safety and efficacy of DMOT4039A is assessed in patients with unresectable pancreatic or platinum-resistant ovarian cancer. By performing a 89Zr-MMOT0530A PET scan prior to treatment with DMOT4039A, the uptake of the tracer in the primary and metastatic tumor lesions can be evaluated. This is likely to provide important information about target expression, whole body drug distribution and the correlation between tumor uptake and response to therapy. Ultimately the use of a 89Zr- MMOT0530A PET as a complimentary tool for patient selection and risk stratification can be evaluated. In part A of this study, the optimal tracer dose of 89Zr- MMOT0530A and schedule for PET imaging will be determined. In part B patients will have PET imaging before treatment in the DMO4993g study on the dose and time points as assessed in part A.
Interventions
DRUG89Zr-MMOT0530A
Injection of 89Zr-MMOT0530A followed by 2 or 3 PET scans at different time points
Sponsors
Amsterdam UMC, location VUmc
Genentech, Inc.
University Medical Center Groningen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/= 18 years of age * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Histologically documented, incurable, locally advanced or metastatic disease for which no standard therapy exists, consisting of one of the following: Unresectable pancreatic ductal adenocarcinoma or platinum-resistant ovarian cancer * Measureable disease, defined as at least one bi-dimensionally measurable non-lymph node lesion \>/= 1 cm in long-axis diameter on spiral CT scan or at least one bi-dimensionally measurable lymph node measuring \>/= 1.5 cm in short-axis diameter on spiral CT scan * Adequate hematological, renal and liver function
Exclusion criteria
* Treatment with anti-tumor therapy, including chemotherapy, biologic, experimental or hormonal therapy, within 4 weeks prior to Day 1 * Known active infection * Current Grade \>/= 2 toxicity (except for alopecia, anorexia and fatigue) from prior therapy or Grade \>/= 2 neuropathy * Untreated or active cerebral nervous system (CNS) metastases * Pregnant or breastfeeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The in vivo biodistribution measured in SUV values and organ pharmacokinetics (PK) of 89Zr-MMOT0530A | Approximately 1 year | * The accumulation, distribution and localization of 89Zr-MMOT0530A in tumor tissue, organs and blood circulation, as assessed by PET. * The quantitative uptake of 89Zr-MMOT0530A expressed in SUV (Standardized Uptake value). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The 89Zr-MMOT0530A tumor uptake measured in SUV related to the response to DMOT4039A therapy according to RECISt 1.1 criteria | Approximately 1 year | The correlation between the 89Zr-MMOT0530A tumor uptake and response to therapy by performing an 89Zr-MMOT0530A PET scan before DMOT4039A therapy, related to CT/MRI response according to RECIST 1.1 criteria. |
| Number of patients with adverse events after 89Zr-MMOT0530A injection as a measure of safety and tolerability | Approximately 1 year | Safety will be assessed by evaluation of incidence of adverse events. |
Countries
Netherlands
Outcome results
None listed