Metastatic Pancreatic Cancer, Pancreatic Cancer
Conditions
Brief summary
Pancreatic cancer is one of the leading causes of cancer deaths in the United States with limited treatment options, especially for those patients with metastatic disease. Combination treatment with cabozantinib and atezolizumab, has demonstrated safety for the treatment of other cancers and has shown promise in preclinical studies utilizing patient derived pancreas organoids. In this study, patients with refractory, metastatic pancreatic cancer will receive combination cabozantinib + atezolizumab and the efficacy of this treatment will be assessed through overall response rate (ORR), disease control rate (DCR), median overall survival (mOS), and median progression free survival (mPFS). Safety and tolerability of combination cabozantinib plus atezolizumab in metastatic pancreatic cancer patients will also be assessed and immune profiling pre- and post-treatment will be explored.
Interventions
DRUGCabozantinib + Atezolizumab
All the subjects will be treated with the combination of cabozantinib and atezolizumab until disease progression, unacceptable toxicity or patient consent withdrawal (whichever occurs first).
Sponsors
University of Arizona
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
1. Stage IV pancreatic adenocarcinoma, confirmed by histology or cytology. (Note: the primary pancreatic adenosarcoma must be confirmed by histology or cytology. The stage IV metastatic disease does not necessarily need to be confirmed by histology or cytology). 2. Clinical and/or radiographic progression on and/or intolerance to and/or ineligibility for treatment with at least one of the following: a fluoropyrimidine or gemcitabine based chemotherapy treatment regimens 3. Radiographically measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Images (MRI or CT Scan) must be completed within 28 days prior to treatment start. 4. Age ≥ 18 years 5. Patients who progress on adjuvant treatment and develop metastatic disease within \< 6 months of adjuvant therapy will be considered as having one prior line of treatment and may be eligible pending subject meeting all other inclusion/
Exclusion criteria
. 6. Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment: 1. Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support. 2. White blood cell count ≥ 2500/µL 3. Platelets ≥ 100,000/µL without transfusion. 4. Hemoglobin ≥ 9 g/dL (≥ 90 g/L). 5. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN) with the following exceptions: Patients with documented liver metastases: AST and ALT ≤ 5 x ULN Patients with documented liver or bone metastases: ALP ≤ 5 x ULN 6. Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN). 7. Serum albumin ≥ 2.8 g/dl 8. (PT)/INR or partial thromboplastin time (PTT) test \< 1.3 x the laboratory ULN 9. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation: Males: (140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72) Females: \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72)\] × 0.85 10. Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g 7. For patients receiving therapeutic anticoagulation, they must have a stable anticoagulant regimen. 8. No clinically significant hypertension as per treating physician or if hypertension, adequate control with anti-hypertensives 9. Negative hepatitis B surface antigen (HBsAg) test at screening 10. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test must be performed for patients who have a positive HCV antibody test. 11. ECOG performance status ≤ 1 12. Recovered to baseline or to CTCAE v5.0 ≤ Grade 1 treatment-related toxicity from prior therapies 13. At least two weeks since last dose of prior treatment 14. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 6 months after the last dose of study treatment. 15. Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating (FSH) level \> 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site. 16. Ability to understand and the willingness to sign a written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate or Stable Disease | Participants will be evaluated for response every 3 cycles (each cycle is 21 days) thereafter until disease progression or death from any cause, whichever occurs first (an average of 6 months) | To evaluate the efficacy of cabozantinib plus atezolizumab in patients with refractory metastatic pancreatic cancer through overall response rate (ORR) changes or stable disease (SD) after 9 weeks of treatment. ORR is defined using the RECIST 1.1 criteria as the proportion of subjects with an investigator-assessed partial or complete response (PR or CR). SD is defined using the RECIST 1.1 criteria: neither sufficient shrinkage (compared to baseline) to qualify for PR or CR nor sufficient increase to qualify for progressive disease (PD; taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Participants will be evaluated for response every 3 cycles (each cycle is 21 days) thereafter until disease progression or death from any cause, whichever occurs first (an average of 6 months) | To evaluate the safety of cabozantinib plus atezolizumab in patients with refractory metastatic pancreatic cancer through the recording of any adverse events (AEs) of grade 3 or higher according to CTCAE version 5.0 and summarized using descriptive statistics. |
| Number of Participants With Toxicities | Participants will be evaluated for response every 3 cycles (each cycle is 21 days) thereafter until disease progression or death from any cause, whichever occurs first (an average of 6 months) | To evaluate the safety of cabozantinib plus atezolizumab in patients with refractory metastatic pancreatic cancer through the recording of a toxicities according to CTCAE version 5.0 and summarized using descriptive statistics. Toxicities are any adverse event considered related or possibly related to either atezolizumab or cabozantinib. |
| Disease Control Rate | Participants will be evaluated for response every 3 cycles (each cycle is 21 days) thereafter until disease progression or death from any cause, whichever occurs first (an average of 6 months) | To assess the disease control rate (DCR) in patients with refractory metastatic pancreatic cancer treated with combination cabozantinib plus atezolizumab. DCR is defined as the percentage of patients who achieve complete response, partial response, or stable disease. DCR is the sum of the complete, partial and stable disease rates. |
| Survival | Participants will be evaluated for response every 3 cycles (each cycle is 21 days) thereafter until disease progression or death from any cause, whichever occurs first (an average of 6 months) | To further define survival outcomes of median overall survival (mOS) and median progression free survival (mPFS) in patients with refractory metastatic pancreatic cancer who receive combination therapy with cabozantinib plus atezolizumab. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRachna Shroff, MD
University of Arizona
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 70 Years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Number of Prior Therapies | 3 Prior therapies STANDARD_DEVIATION 2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 29 / 30 |
| serious Total, serious adverse events | 19 / 30 |
Outcome results
None listed