Pancreatic Adenocarcinoma, Metastatic Pancreatic Cancer, Basal Cell Neoplasm
Conditions
Keywords
safety, tolerability, efficacy, EGFR inhibitors, gemcitabine, nab-paclitaxel
Brief summary
This Phase I/II clinical trial is being conducted at multiple centers to find out whether adding a low dose of EGFR blocking drugs to the standard chemotherapy combination of gemcitabine and nab paclitaxel (GnP) is safe, tolerable, and helpful for people with advanced pancreatic cancer. All participants are first tested with a tool called PurIST, which classifies tumors as either "basal-like" or "classical." People with basal-like tumors will receive GnP plus erlotinib during Phase I so researchers can determine the safest and most effective dose. Once that dose is identified, the study moves to Phase II, where people with basal-like tumors will be randomly assigned to receive either GnP alone or GnP with erlotinib. Phase II may also test new drug combinations if new treatments become approved during the study period. Overall, the trial plans to include up to about 52 basal-like patients in Phase I, roughly 82 basal-like patients in Phase II, and at least 52 classical patients, with the possibility of enrolling more if needed. People whose tumors are classified as classical will continue with standard treatments recommended by their doctors or other clinical trials. Across the entire study, researchers will carefully track long-term outcomes such as overall survival, how long patients live before the cancer progresses, and how well their tumors respond to treatment.
Interventions
DRUGGemcitabine
1000 mg/m2, intravenously on day 1 and day 15, for subjects with basal-like cell type pancreatic carcinoma.
DRUGNab paclitaxel
125 mg/m2 intravenously on day 1 and day 15 for subjects with basal-like cell type pancreatic carcinoma.
DRUGErlotinib
50 mg per oral daily. for subjects with basal-like cell type pancreatic carcinoma.
DRUGNALIRIFOX
Subjects with classical pancreatic adenocarcinoma will receive. NALIRIFOX is liposomal irinotecan with 5-fluorouracil/leucovorin and oxaliplatin. Dosing and plan will be decided by the treating physician.
DRUGFolfirinox
Subjects with classical pancreatic adenocarcinoma will receive. Dosing and plan will be decided by the treating physician.
Sponsors
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
a two-stage U-BOIN design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent was obtained to participate in the study and HIPAA authorization for release of personal health information. Subjects is willing and able to comply with study procedures based on the judgment of the investigator. * Age ≥ 18 years at the time of consent. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 Histological or cytological evidence/confirmation of unresectable, borderline resectable, or metastatic (basal-like and classical) pancreatic adenocarcinoma. * The subject must consent to a mandatory pre-study biopsy if archival tissue is not available or sufficient. * Subjects may have received prior standard-of-care (SOC) neoadjuvant therapy and may have received up to two cycles of first-line FOLFIRINOX or NALIRIFOX. * A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study treatment have been off of corticosteroids for ≥ 2 weeks and are asymptomatic.
Exclusion criteria
* Disease is not measurable according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 * Not having histological or cytological evidence/confirmation of metastatic pancreatic adenocarcinoma. * Treatment with any investigational drug or prior cancer treatment within 28 days prior to study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events per Common Terminology Criteria for Adverse Events (NCI-CTCAE) | First day of study treatment through the 28 days after last treatment | Adverse Events (AEs) will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, in Phase I subjects with basal-like settings. The number of participants with adverse events (AE) will be reported. . |
| Dose-limiting toxicity (DLT) | Up to 28 days | DLTs are defined using adverse events as at least possibly related to erlotinib administration in Phase I subjects. If an apparent DLT is clearly due to an underlying disease and is unrelated to the product infusion, then the investigator will specify that the event is not a DLT. Toxicities related to treatment and assessed Adverse Events per Common Terminology Criteria for Adverse Events (NCI-CTCAE) will be used for assessment. The safety evaluation period for dose-limiting toxicity (DLT) assessment and determination of optimal best dose (OBD) will encompass toxicities related to treatment with low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel starting on the day of treatment initiation through the end of treatment. |
| Overall survival- classical metastatic pancreatic adenocarcinoma | 2 years | Overall survival of subjects with classical metastatic pancreatic adenocarcinoma is defined as the length of time from the start of treatment until death. |
| Progression-free survival | 2 years | Progression-free survival in subjects on low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel with basal-like metastatic pancreatic adenocarcinoma is defined as the length of time between the start of treatment until progression or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The number of Adverse Events (AEs) in subjects with basal like pancreatic carcinoma | First day of study treatment through the 28 days after last treatment | The number of Adverse Events (AEs) in subjects with basal-like pancreatic carcinoma treated with low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel as defined by CTCAE v5. |
| Overall survival in subjects with basal-like metastatic pancreatic adenocarcinoma | 2 years | Overall survival in subjects with basal-like metastatic pancreatic adenocarcinoma on low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel is defined as the length of time from the start of treatment until death (basal-like arm only). |
| The objective response in subjects with classical pancreatic adenocarcinoma | Up to 12 weeks | The objective response in subjects with classical pancreatic adenocarcinoma treated with standard-of-care triplet chemotherapy (FOLFIRINOX or NALIRIFOX) as defined as complete response (CR) + partial response (PR) as determined by RECIST 1.1 criteria. |
| The number of Adverse Events (AEs) in subjects with classical pancreatic adenocarcinoma | First day of study treatment through the 28 days after last treatment | The number of Adverse Events (AEs) in subjects with classical pancreas carcinoma treated with standard-of-care triplet therapy as defined by CTCAE v5.0. |
| Progression-free survival (PFS) in subjects with classical pancreatic adenocarcinoma | 2 years | Progression-free survival (PFS) after standard-of-care triplet chemotherapy (FOLFIRINOX or NALIRIFOX) in patients with classical metastatic pancreatic adenocarcinoma is defined as the length of time between the start of standard-of-care triplet therapy until progression or death. |
| The objective response rate- basal-like pancreatic carcinoma | Up to 12 weeks | The objective response rate in Stage 2 subjects with basal-like histology, treated with low-dose erlotinib at the OBD when administered with bi-weekly gemcitabine/nab-paclitaxel as defined as complete response (CR) + partial response (PR) as determined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1 criteria. RECIST indicates if the subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), 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. |
Countries
United States
Contacts
CONTACTCatherine A Griffin
PRINCIPAL_INVESTIGATORAshwin Somasundaram, MD
UNC Lineberger Comprehensive Cancer Center
Outcome results
None listed