Pancreatic Cancer
Conditions
Brief summary
The main purpose of this study is to look at the potential effects of paricalcitol (a drug similar to vitamin D) and nivolumab on pancreatic tumors in patients who are treated with gemcitabine and abraxane. The study will also look at the safety of including paricalcitol and nivolumab as part of the gemcitabine and abraxane chemotherapeutic regimen.
Interventions
DRUGNivolumab
Before Surgery Wks 1 &3, After Surgery Wks 1 &3
DRUGNab-Paclitaxel
Wks 1,2,3 before surgery and Wks 1, 2,3 after surgery
DRUGGemcitabine
Wks 1,2,3 before surgery and Wks 1,2,3 after surgery
DRUGParicalcitol
Wks 1,2,3, 4 before surgery and Wks 1,2,3 after surgery
Sponsors
Abramson Cancer Center at Penn Medicine
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previously untreated, apparently resectable adenocarcinoma of the pancreas at registration. * Age greater than or equal to 18 years * ECOG performance status of 0-2. * Standard laboratory criteria for hematologic, biochemical, and urinary indices within a range that, in the opinion of the physician, clinically supports enrollment of the subject on the trial. a. Note: subjects must have: Creatinine \< 2xULN, Neutrophils \>1.5x109/L, total bilirubin \< 3xULN, AST \<5xULN, ALT \<5xULN, and Platelets \>100,000/mm3 * Ability to provide written informed consent
Exclusion criteria
* Subjects with hypercalcemia (blood levels greater than 11.5 mg/dL). In subjects creatinine clearance \<60mL/min, blood calcium levels must be 9.5 mg/dL or lower. * Subjects who are currently pregnant, planning to become pregnant, or breast-feeding 1. Females participants of child-bearing potential are required to use an effective contraception method (see Appendix A) or abstain from intercourse during treatment and for at least 5 months following the last dose 2. Males participants with partners of child-bearing potential are required to use an effective contraception method (see Appendix A) or abstain from intercourse during treatment and for at least 5 months following the last dose 3. Subjects who, in the opinion of the physician, would not be clinically appropriate for receipt of the therapy regimen associated with participation 4. Subjects with contraindications to immune checkpoint therapy, as follows: <!-- --> 1. Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity 2. Prior organ allograft or allogeneic bone marrow transplantation 3. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication 4. Active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma, atopic dermatitis, or endocrinopathies manageable by hormone replacement; other autoimmune conditions may be allowable at the discretion of the principal investigator 5. Condition requiring systemic treatment with either corticosteroids * Systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted. Steroids as anti-emetics for chemotherapy are strongly discouraged (see section 5.1.3) * Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | 18 months | An adverse event (AE) was defined as any unfavorable symptom, sign, illness or experience that occurs at any dose and develops or worsens in severity during the course of the study. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 3 months | Objective response rate by RECIST v 1.1 after neoadjuvant chemotherapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. |
| Progression-free Survival | 1 year | Proportion of patients alive without progression 1 year from the start of study therapy |
| Proportion of Patients Undergoing Surgery | 3 months | Proportion of patients who underwent surgical resection after receiving neoadjuvant therapy |
| Overall Survival | 1 year | Overall survival 1 year after the initiation of study therapy |
| Proportion of Margin Negative Surgical Resections | 3 months | Proportion of patients undergoing surgical resection with surgical margins uninvolved by tumor |
Countries
United States
Participant flow
Recruitment details
Treatment naïve patients with apparently resectable adenocarcinoma of the pancreas with the epithelial subtype were enrolled at the University of Pennsylvania from July 2020 through April 2022.
Pre-assignment details
Patients pre-treated with chemotherapy nivolumab were randomized 1:1 to receive (Arm A) or not receive (Arm B) weekly intravenous paricalcitol. 3 patients were enrolled in the study, therefore, the target enrollment of 20 patients was not reached.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Nivolumab: Before Surgery Wks 1 &3, After Surgery Wks 1 &3
Nab-Paclitaxel: Wks 1,2,3 before surgery and Wks 1, 2,3 after surgery
Gemcitabine: Wks 1,2,3 before surgery and Wks 1,2,3 after surgery
Paricalcitol: Wks 1,2,3, 4 before surgery and Wks 1,2,3 after surgery | 2 |
| Arm B Nivolumab: Before Surgery Wks 1 &3, After Surgery Wks 1 &3
Nab-Paclitaxel: Wks 1,2,3 before surgery and Wks 1, 2,3 after surgery
Gemcitabine: Wks 1,2,3 before surgery and Wks 1,2,3 after surgery | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Arm B | Total | Arm A |
|---|---|---|---|
| Age, Continuous | 57 years | 57 years | 58.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 1 / 2 | 1 / 1 |
Outcome results
Primary
Number of Adverse Events
An adverse event (AE) was defined as any unfavorable symptom, sign, illness or experience that occurs at any dose and develops or worsens in severity during the course of the study. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Time frame: 18 months
Population: participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A | Number of Adverse Events | 19 number of adverse events | Standard Deviation 4.2 |
| Arm B | Number of Adverse Events | 27 number of adverse events | Standard Deviation 0 |
Secondary
Objective Response Rate
Objective response rate by RECIST v 1.1 after neoadjuvant chemotherapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Objective Response Rate | 1 Participants |
| Arm B | Objective Response Rate | 1 Participants |
Secondary
Overall Survival
Overall survival 1 year after the initiation of study therapy
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Overall Survival | 2 Participants |
| Arm B | Overall Survival | 1 Participants |
Secondary
Progression-free Survival
Proportion of patients alive without progression 1 year from the start of study therapy
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Progression-free Survival | 2 Participants |
| Arm B | Progression-free Survival | 1 Participants |
Secondary
Proportion of Margin Negative Surgical Resections
Proportion of patients undergoing surgical resection with surgical margins uninvolved by tumor
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Proportion of Margin Negative Surgical Resections | 1 Participants |
| Arm B | Proportion of Margin Negative Surgical Resections | 1 Participants |
Secondary
Proportion of Patients Undergoing Surgery
Proportion of patients who underwent surgical resection after receiving neoadjuvant therapy
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Proportion of Patients Undergoing Surgery | 2 Participants |
| Arm B | Proportion of Patients Undergoing Surgery | 1 Participants |