Cabozantinib and Erlotinib for Patients With EGFR and c-Met Co-expressing Metastatic Pancreatic Adenocarcinoma
- Conditions
- Pancreatic Adenocarcinoma Metastatic
- Interventions
- Registration Number
- NCT03213626
- Lead Sponsor
- Patrick Joseph Loehrer Sr.
- Brief Summary
This is an open-label, single arm, phase II trial. Safety will be monitored on an ongoing basis. Laboratory testing (chemistry, hematology tests) will be performed every 2 weeks for the first 8 weeks followed by assessments every 4 weeks. Other safety evaluations including EKGs, urinalysis, coagulation and thyroid function studies will be performed at regular intervals.
Adverse event seriousness, severity grade, and relationship to study treatment will be assessed by the investigator. Severity grade will be defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Tumors will be assessed by contrast enhanced CT or MRI every 8 weeks. Pre-treatment tissue will be obtained via CT-guided FNA biopsy or collected during resection. However, archival tissue will also be requested, when available and if adequate for testing. Post-treatment tissue will be obtained on Day 15 (i.e., Week 3/Day 1) via CT-guided FNA biopsy. All tumor tissue from eligible patients will be utilized for the correlative studies which are outlined in this trial.
Each subject's course will consist of three periods:
* A Pre-Treatment Period in which subjects are consented and undergo screening assessments to be qualified for the study;
* A Treatment Period in which subjects receive study treatment and undergo study assessments. Patients who meet the eligibility criteria will be treated with cabozantinib orally at 40 mg daily and erlotinib orally at 100 mg daily without breaks;
* A Post-Treatment Period in which subjects no longer receive study treatment but undergo follow-up study assessments and contacts.
- Detailed Description
Primary Objective The primary objective of this trial is to demonstrate a radiographic response rate of 15% or greater for the combination in a selected population.
Secondary Objectives
The secondary objectives of this trial are:
* To estimate progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), overall survival (OS); and
* To assess safety and tolerability of this combination in the target patient population.
Correlative Objectives
The following tests will be performed on blood and tumor tissue samples collected during this trial to correlate with PFS and OS:
* c-Met and EGFR mRNA by RT-qPCR
* plasma HGF and soluble Met receptor
* c-Met and EGFR phosphoprotein levels by IHC
* KRAS mutation status
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 7
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cabozantinib + erlotinib Cabozantinib 40 MG - Cabozantinib + erlotinib Erlotinib 100Mg Tab -
- Primary Outcome Measures
Name Time Method Objective (Radiographic) Response 8 weeks Percent of patients with Objective response and the Binomial Exact 95% confidence interval. Objective response is defined as having a best response of Complete Response (defined as disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10mm) or Partial Response (defined as at least a 30% decrease in the sum of diameters of target lesions from the baseline sum diameters) by RECIST v1.1 criteria.
- Secondary Outcome Measures
Name Time Method Disease Control Rate 8 weeks Percent of patients achieving disease control and the Binomial Exact 95% confidence interval. Disease control is defined as having a best response of Complete Response (defined as disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10mm) or Partial Response (defined as at least a 30% decrease in the sum of diameters of target lesions from the baseline sum diameters) or Stable Disease for at least 4 months (defined by neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression) by RECIST v1.1 criteria.
Progression Free Survival 2 years Duration of time from the start of treatment to time of documented progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Patients who do not progress or die will be censored on their last evaluation date. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated.
Overall Survival 2 years Duration of time from the start of treatment to time of death due to any causes. Patients who do not die will be censored on their last known alive date. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated.
Treatment Related Adverse Events Grade 3 or Above Up to 5 months Number of unique patients who had a treatment related (possible, probable or definite) adverse events with grade \>= 3.
Trial Locations
- Locations (2)
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Indiana University Health Hospital
🇺🇸Indianapolis, Indiana, United States