Pancreatic Cancer, Pancreatic Cancer Metastatic
Conditions
Brief summary
This is a phase 1, open-label clinical trial determining the recommended Phase 2 dose of Gemcitabine with Nab-paclitazel with or without Pitavastatin in subjects with unresectable pancreatic adenocarcinoma (uPDAC). These are subjects who are already receiving Gemcitabine for treatment of their disease.
Interventions
DRUGPitavastatin
Given PO
Sponsors
University of California, Irvine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose Escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years old * Provision of a signed and dated ICF by the participant * Has a diagnosis of histologically or cytologically confirmed metastatic, recurrent, or locally advanced PDAC * Receiving a gemcitabine-based treatment regimen for a minimum of 2 and a maximum of 4 cycles without radiographic progression (ie SD or better). * Measurable disease per RECIST 1.1 * Adequate organ (hematologic, hepatic, renal) function defined below: * Hemoglobin ≥ 9.0 g/dL (transfusion is allowed) * Platelets ≥ 100,000/mcL (transfusion is allowed) * ANC ≥ 1500/mcL * AST/ALT ≤ 3 x ULN (≤ 5 x ULN is allowable in cases of liver metastasis or Gilbert's Syndrome) * Serum bilirubin ≤ 1.5 x ULN * Serum albumin ≥ 3.0 g/dL * Serum creatinine ≤ 1.5 x ULN OR creatinine clearance \> 60 mL/min * ECOG PS 0-2 * 2 lines or less of prior treatment. Prior curative intent treatment (surgery and, if given in the adjuvant setting, systemic therapy and/or radiation) is permitted, regardless of time to recurrence, and does not constitute a line of therapy. This includes participants with residual disease after surgery, who received systemic therapy, chemoembolization, or radiotherapy.
Exclusion criteria
* Uncontrolled significant clinical illness * Clinically significant autoimmune disease * Major surgery within 4 weeks of the first dose of registration * Known prior malignancy active within the previous 3 years, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. * Concomitant use of statin therapy (to be discontinued 2 weeks prior to the start of C1D1). * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HbsAg) are eligible. * Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. * Patients with a known history of HIV. * Known active metastases in the central nervous system (unless stable by brain imaging studies for at least 1 month after last treatment) * Patients with QT interval corrected by Fridericia's formula (QTcF) \> 470 msec for both men and women on screening ECG are excluded. * A woman of childbearing potential who has a positive pregnancy test prior to initiating study treatment. * Breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening visit through 5 months after the last dose of study treatment. * Medicines known to inhibit or induce either CYP2C8, CYP2C9, or CYP3A4 * History of prior organ or stem cell transplant. * Has an active infection requiring systemic therapy. Systemic treatment used prophylactically is allowable. * Patients who are unable to swallow or retain oral medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase II Dose | 2 years | Determine the recommended phase II dose (RP2D) of Pitavastatin in combination with Gemcitabine and nab-paclitaxel in treatment of uPDAC and determine any adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients with Adverse Events | 2 years | Number of Patients who received at least one dose of Gemcitabine and Nab-paclitaxel with Pitavastatin with any reported Adverse Events (AEs) using the CTCAE version 5.0 for reporting of nonhematologic AEs and modified criteria for hematologic AEs. |
| Number of Patients who Discontinued Treatment Due to Reported Adverse Events | 2 years | Number of Patients who received at least one dose of Gemcitabine and Nab-paclitaxel with Pitavastatin requiring discontinuation of therapy due to reported AEs using the CTCAE version 5.0 for reporting of nonhematologic AEs and modified criteria for hematologic AEs. |
| Objective Response Rate (ORR) by RECIST v1.1 | 2 years | Sum of Complete Response (CR) and Partial Response (PR) by RECIST v 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. ORR = CR + PR for each dose cohort. |
| Progression-Free Survival | 2 years | Determine the progression-free survival (PFS) for each cohort. PFS is measured from the date of randomization to the first date of disease progression. |
Countries
United States
Contacts
CONTACTChao Family Comprehensive Cancer Center University of California, Irvine
CONTACTUniversity of California Irvine Medical
PRINCIPAL_INVESTIGATORJennifer Valerin, MD, PhD
Chao Family Comprehensive Cancer Center
Outcome results
None listed