Pancreatic Ductal Adenocarcinoma
Conditions
Brief summary
This is a phase II open-label study evaluating the efficacy and safety of nab-paclitaxel cisplatin, and gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma.
Detailed description
This is a phase II open-label study evaluating the efficacy and safety of nab-paclitaxel cisplatin, and gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma. An individual cycle of therapy will be defined as Days 1 and 8 every 21 days. Multiple cycles may be administered until the patient is withdrawn from therapy. Overall response rates as well as individual categories of response complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) will be determined using RECIST 1.1. Time-to-event endpoints, including progression-free survival (PFS) and overall survival (OS) will be assessed using the Kaplan-Meier method. Evaluation of stable disease at 9 weeks will also be assessed. Toxicity (adverse events) will be recorded using the NCI CTCAE, version 5.0.
Interventions
DRUGNabCG (nab-Paclitaxel + Cisplatin + Gemcitabine)
Cisplatin 25mg/m2 in 500 mL of NS over 60 minute IV infusion on days 1 and 8 repeated every 21 days. Gemcitabine 1000mg/m2 in 500 mL\* over 30 minute IV infusion on days 1 and 8 repeated every 21 days. Post cisplatin hydration: IV fluids up to 1000 mL (with additives as clinically indicated) IV given as infusion on days cisplatin is administered on days 1 and 8 repeated every 21 days.
Sponsors
HonorHealth Research Institute
Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 105 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years of age; male or female 2. Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. 3. Capable of providing informed consent and complying with trial procedures. 4. Karnofsky Performance Status (KPS) of ≥ 70%. 5. Life expectancy ≥ 12 weeks. 6. Measurable tumor lesions according to RECIST 1.1 criteria. 7. \< Grade 2 pre-existing peripheral neuropathy per NCI CTCAE, Version 5.0 8. Patient has acceptable coagulation status as indicated by an international normalized ratio (INR) ≤1.5 x ULN. Patients on anticoagulation can be included at the discretion of the investigator. 9. Patients must have normal organ and marrow function as defined below: * Absolute neutrophil count ≥1,500/mm3 * Platelet concentration ≥100,000/mm3 with no platelet transfusions within 7 days prior to laboratory sample * Hemoglobin \> 9.0g/dL * Hematocrit level \> 27% * Total bilirubin within 1.25 times institutional upper limit of normal (ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 10 × institutional ULN * Serum creatinine \<1.5 mg/dl 10. Females of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy \[the surgical removal of the uterus\] or bilateral oophorectomy \[the surgical removal of both ovaries\] or (2) has not been naturally postmenopausal for at least 24 consecutive months \[i.e., has had menses at any time during the preceding 24 consecutive months\]) must: 1. Either commit to true abstinence\* from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting IP therapy (including dose interruptions), and while on study medication or for a longer period if required by local regulations following the last dose of IP; and 2. Have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy. This applies even if the subject practices true abstinence\* from heterosexual contact. 11. Male subjects must practice true abstinence\* or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following discontinuation from study treatment, even if he has undergone a successful vasectomy.
Exclusion criteria
1. Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatments in the neoadjuvant and/or adjuvant setting with gemcitabine and/or Fluorouracil (5-FU) based therapies or gemcitabine and/or 5FU administered as a radiation sensitizer are allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. 2. Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment. 3. Exposure to any investigational agent within 4 weeks prior to initiation of study treatment. 4. Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit). 5. History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for ≥5 years. 6. Current, serious, clinically significant cardiac arrhythmias as determined by the investigator. 7. History of HIV infection. 8. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals. 9. Major surgery within 4 weeks prior to initiation of study treatment. 10. Any condition in the opinion of the principal investigator that might interfere with the patient's participation in the study or in the evaluation of the study results. 11. Any condition in the opinion of the principal investigator that is unstable and could jeopardize the patient's participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12- Month Overall Survival (OS) | 12 months | Evaluate the 12-month OS rate in patients with metastatic Pancreatic ductal adenocarcinoma (PDA) treated with nab-paclitaxel plus cisplatin plus gemcitabine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity Adverse Events (Grade ≥ 3) | 12-months | Adverse events (grade ≥ 3) that were possibly, probably, or definitely related to study drug or study procedure, by severity (highest grade per person, per event term), n (%) |
| Complete Response Rate (CR) | 63 days | Complete response rate as defined by CT scan using RECIST 1.1 criteria and CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) down to normal limits (from at least \> 2X ULN). |
| Disease Control Rate (CR, PR, SD) at 9 Weeks | 63 days | To determine the preliminary efficacy (Disease control rate of CR+ PR+SD X 9 weeks) of the combination of nanoparticle albumin- bound paclitaxel + cisplatin + gemcitabine (NABPLAGEM) in patients with stage IV metastatic pancreatic cancer.complete response rate( RECIST 1.1), disease control rate at 9 weeks, Change and rates of normalization in CA 19-9 (or Ca125 or CEA if not expressers of CA 19-9) |
| Change in CA 19-9 or CA 125 | End of Study (36 months) | Change in carbohydrate antigen 19-9 (CA 19-9) or cancer antigen 125 (CA 125). Both CA 19-9 and CA 125 are markers of tumor burden and treatment response. |
| Rate of Tumor Marker Normalization | 12 months | Complete response rate as defined by CT scan using RECIST 1.1 criteria and CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) down to normal limits (from at least \> 2X ULN). |
| Quality of Life: MD Anderson Symptom Inventory (MDASI-GI) | Baseline to Midpoint (C4/D1) | The MD Anderson Symptom Inventory for gastrointestinal cancer (MDASI-GI) is a site-specific MDASI module. Along with the core MDASI's 13 symptom items and 6 interference items, the MDASI-GI also assesses 5 symptoms specific to gastrointestinal cancer. Average Symptom severity Scores were measured to assess change in symptoms over time (Core Symptom Scoring: 0 - Not Present to 10 - As Bad as you can imagine; Overall symptom distress (Interference) Scoring: 0-Did not interfere to 10-Interfeard completely; Gastrointestinal Module: 0 (symptom has not been present) to 10 (the symptom was as bad as you can imagine it could be)). |
| Pain Control: Brief Pain Inventory (BPI) | Baseline to Midpoint (C4/D1) | The Brief Pain Inventory (BPI) rapidly assesses the severity of pain and its impact on functioning. The BPI has been translated into dozens of languages, and it is widely used in both research and clinical settings. Average scores were measured (Scoring scale: Pain Severity: 0 - No Pain to 10 - Pain as bad as you can imagine; Pain Interference 0-Does not interfere to 10 - Completely Interferes) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORGayle Jameson, ACNP-BC
HonorHealth Research Institute
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 25 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous Median (range) | 66.8 years |
| Brief Pain Inventory (BPI) Pain interference | 3.1 pain score STANDARD_DEVIATION 2.9 |
| Brief Pain Inventory (BPI) Pain severity | 2.7 pain score STANDARD_DEVIATION 2.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| KPS - Karnofsky Performance Status 100% | 5 Participants |
| KPS - Karnofsky Performance Status 70% | 2 Participants |
| KPS - Karnofsky Performance Status 80% | 17 Participants |
| KPS - Karnofsky Performance Status 90% | 18 Participants |
| MD Anderson's Symptom Inventory-GI (MDASI-GI) Core symptom severity score | 2.5 symptom score STANDARD_DEVIATION 1.7 |
| MD Anderson's Symptom Inventory-GI (MDASI-GI) Gastrointestinal module score | 1.8 symptom score STANDARD_DEVIATION 1.7 |
| MD Anderson's Symptom Inventory-GI (MDASI-GI) Overall symptom distress (interference) score | 3.1 symptom score STANDARD_DEVIATION 2.9 |
| Neutrophil-to-lymphocyte ratio (NLR) ≤ 5 | 22 Participants |
| Neutrophil-to-lymphocyte ratio (NLR) > 5 | 20 Participants |
| Primary tumor location on pancreas Body | 15 Participants |
| Primary tumor location on pancreas Head | 16 Participants |
| Primary tumor location on pancreas Head and Body | 1 Participants |
| Primary tumor location on pancreas Tail | 10 Participants |
| Prior Cancer Treatment Adjuvant chemotherapy | 4 Participants |
| Prior Cancer Treatment Prior PDA surgery | 3 Participants |
| Prior Cancer Treatment Radiotherapy | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 37 Participants |
| Region of Enrollment United States | 42 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 28 Participants |
| Tumor Markers cancer antigen (CA) 19-9 (or CA 125, or CEA) CA 125 > 35* | 5 Participants |
| Tumor Markers cancer antigen (CA) 19-9 (or CA 125, or CEA) CA 19-9 < 35 | 6 Participants |
| Tumor Markers cancer antigen (CA) 19-9 (or CA 125, or CEA) CA 19-9 > 35 | 35 Participants |
| Tumor Markers cancer antigen (CA) 19-9 (or CA 125, or CEA) CA 19-9 not collected | 1 Participants |
| Tumor Markers cancer antigen (CA) 19-9 (or CA 125, or CEA) CEA > 3* | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 37 / 42 |
| other Total, other adverse events | 42 / 42 |
| serious Total, serious adverse events | 28 / 42 |
Outcome results
None listed