Locally Advanced Pancreatic Carcinoma(LAPC)
Conditions
Brief summary
This is a phase II, single-arm, open-label, clinical study to investigate the efficacy and tolerability of a combination of liposomal irinotecan (nal-IRI) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-nal-IRI) for treatment of patients with locally advanced pancreatic carcinoma (LAPC).
Detailed description
This is a phase II, single-arm, open-label, clinical study to investigate the efficacy and tolerability of a combination of liposomal irinotecan (nal-IRI) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-nal-IRI) for treatment of patients with locally advanced pancreatic carcinoma (LAPC). Each subject will be screened for eligibility by evaluation including medical history, physical examination, performance status, blood tests, computed tomographic (CT) scans, and electrocardiogram. Within 28 days of screening, the consented subjects will have a central venous access device placed and then start treatment. For every 2-week cycle of FOLFOX-nal-IRI, each subject will receive nal-IRI (irinotecan free base 50 mg/m2 intravenously over 90 minutes), oxaliplatin (60 mg/m2 intravenously over 2 hours), leucovorin (400 mg/m2 intravenously over 2 hours), and 5-fluorouracil 2,400 mg/m2 intravenously over 46 hours). Tumor response/surgical assessment will be evaluated after every 4 cycles of treatment with CT scans using RECIST 1.1 criteria. If the tumor becomes surgically resectable and the subject is a surgical candidate as determined by a multidisciplinary team, the subject will undergo surgery (at which point he/she would enter survival follow-up). If the tumor remains unresectable and there is no tumor progression, each subject will be treated up to a total of 12 cycles of FOLFOX-nal-IRI. Following treatment with 12 cycles of FOLFOX-nal-IRI, if tumor remains unresectable, the subjects may receive further treatment (chemotherapy using the same regimen or of the treating physician's choice, or chemoradiation therapy) or observation as determined by the physician. During the course of treatment, if the subjects develop unacceptable toxicity and/or disease progression, the treatment will be discontinued, and the subjects will be further managed at the discretion of the treating oncologists.
Interventions
DRUGFOLFOX regimen
FOLFOX (Oxaliplatin, Leucovorin, 5-Fluorouracil)
DRUGLiposomal Irinotecan
Liposomal Irinotecan
Sponsors
Ipsen
Nelson Yee
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a phase II, single-arm, open-label, clinical study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. * Age ≥ 18 years at the time of consent. * ECOG Performance Status of 0-1 within 28 days prior to registration. * Histological or cytological confirmation of pancreatic carcinoma. * Measurable disease according to RECIST v1.1 within 28 days prior to registration. * Previously untreated pancreatic carcinoma considered as locally advanced unresectable according to NCCN guidelines. * Demonstrate adequate organ function as defined in the table below; All screening labs to be obtained within 14 days prior to initiation of study treatment. * Hematological * Absolute Neutrophil Count (ANC): \>/=1500/uL * Hemoglobin (Hgb): \>/=8 g/dL with blood transfusion permitted * Platelet (Plt): \>/=100,000/uL * Renal * Serum creatinine: \</=1.5 x upper limit of normal (ULN) OR * Calculated creatinine clearance using the Cockcroft-Gualt formula: \>/=50 mL/min for subjects with creatinine levels \>1.5 ULN * Hepatic * Total bilirubin: \</=1.5 x ULN (biliary drainage is allowed for biliary obstruction). Patients with Gilbert's syndrome with a total bilirubin \</=3.0 x ULN and direct bilirubin within normal limits are permitted * Aspartate aminotransferase (AST): \</=2.5 x ULN * Alanine aminotransferase (ALT): \</=2.5 x ULN * Albumin: \>/=3.0 g/dL * Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT): \</=1.5 x ULN unless subject is receiving anticoagulant therapy, as long as PT, INR or PTT is within therapeutic range of intended use of anticoagulants * Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days of study registration and within 72 hours of Cycle 1 Day 1. NOTE: Female subjects are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. * Female subjects of childbearing potential and males must be willing to abstain from behaviors that could lead to pregnancy (heterosexual activity, sperm donation, in vitro fertilization, etc.) or to use 2 forms of effective methods of contraception from the time of informed consent until 9 months (females) or 6 months (males) after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. * As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. The subject should be able to understand the purpose and risks of the study and provide a signed and dated informed consent form.
Exclusion criteria
* Known hypersensitivity to irinotecan liposome, other liposomal products, oxaliplatin, 5-fluorouracil, leucovorin, or any ingredients in those preparations. * Pre-existing peripheral neuropathy (Grade 3 or 4) during screening. * Major surgery within 4 weeks of starting treatment. * Active uncontrolled cardiac arrhythmia or congestive heart failure (class 3 or 4 as defined by the New York Heart Association Functional Classification); or history of myocardial infarction, unstable angina; or acute coronary syndrome within 6 months prior to enrollment. * Known history of human immunodeficiency virus (HIV), or hepatic cirrhosis caused by active infection with hepatitis B virus (HBV, as defined by HBsAg positivity or positive DNA). Testing is not required for study entry if there is no clinical suspicion. Note: hepatic cirrhosis caused by other factors (ex. alcoholic cirrhosis) may be considered on a case-by-case basis if, in the opinion of the treating investigator, the disease is unlikely to compromise the subject's safety or put the study outcomes at unnecessary risk. * Any medical condition, life-threatening illness, or organ dysfunction, which in the investigator's opinion, can compromise the subject's safety or put the study outcomes at unnecessary risk. * Uncontrolled active systemic infection. * Concomitant medications that are prohibited in this study and they cannot be switched to alternative medications. * Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). * Known additional malignancy that is active and/or progressive requiring treatment within 2 years of screening for this study; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, low-grade prostate cancer, or other cancer for which the subject has been disease-free for at least five years. Additional exceptions could be considered if agreed by sponsor-investigator and site investigator assuming the disease is considered extremely unlikely to confound evaluation of disease status. * Treatment with any investigational drug within 30 days prior to registration, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing of this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Up to 22 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Disease Control Rate (DCR) = CR +PR+SD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) at 16 Weeks | 16 weeks | 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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Overall Response (OR) = CR + PR. |
| Objective Response Rate (ORR) at 24 Weeks | 24 weeks | 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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Overall Response (OR) = CR + PR. |
| Stable Disease Rate (SDR) at 8 Weeks | 8 Weeks | 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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Stable disease rate (SDR) is determined by the proportion of subjects with no progression of disease as defined by RECIST 1.1, at 8 weeks following initiation of FOLFOX-nal-IRI. |
| Stable Disease Rate (SDR) at 16 Weeks | 16 Weeks | 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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Stable disease rate (SDR) as determined by the proportion of subjects with no progression of disease as defined by RECIST 1.1, at 16 weeks following initiation of FOLFOX-nal-IRI. |
| Stable Disease Rate (SDR) at 24 Weeks | 24 Weeks | 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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Stable disease rate (SDR) as determined by the proportion of subjects with no progression of disease as defined by RECIST 1.1, at 24 weeks following initiation of FOLFOX-nal-IRI. |
| Objective Response Rate (ORR) at 8 Weeks | 8 weeks | 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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Overall Response (OR) = CR + PR. |
| Response of Serum CA19-9 Levels | Up to 7 months | A CA 19-9 test measures the amount of a protein called CA19-9 (cancer antigen 19-9) in a sample of blood. Healthy people can have small amounts of CA 19-9 in their blood. High levels of CA 19-9 are often a sign of pancreatic cancer. Increasing CA 19-9 levels mean the tumor is growing, whether decreasing CA 19-9 levels may mean the tumor is shrinking. The Mean of the percentage change from baseline in serum CA19-9 levels associated with best confirmed response (PR, SD, PD) per RECIST 1.1 are reported in the outcome measure data table. |
| Progression-Free Survival (PFS) | Up to 22 months | 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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Progression-free survival (PFS) as determined by the time interval from the date of first dose of study drug to first documented disease progression or death from any cause, whichever occurs first. |
| Overall Survival (OS) | Up to 31 months | Overall survival (OS) is defined as time from the first dose of study drug to date of death from any cause. |
| Number of Participants With Adverse Events | Up to 7 months | Adverse events will be assessed to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5. |
| Quality of Life (QoL) Assessment: Global Health Status (EORTC QLQ-C30) | Treatment Cycle 1 (14 days), Treatment Cycle 5 (70 days), Treatment Cycle 9 (126 days), Follow-Up (7 Months) | This secondary outcome measure evaluates overall quality of life using the Global Health Status scale from the EORTC QLQ-C30. Scores range from 0 to 100, with higher scores indicating better global health and quality of life. Mean (SD) scores are reported by assessment period, including only those participants who reached the defined time points (e.g., Cycle 9). |
| Proportion of Subjects Able to Undergo Surgical Resection | 12 months | Rate of resectability as determined by the proportion of subjects who undergo surgical resection of tumors. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FOLFOX + Irinotecan Oxaliplatin 60 mg/m2 Intravenously (IV) over 2 hours
Liposomal Irinotecan (free base) 50 mg/m2 IV over 90 minutes after completion of oxaliplatin
Leucovorin 400 mg/m2 IV over 30 minutes after completion of liposomal irinotecan
5-Fluorouracil 2,400 mg/m2 IV over 46 hours via infusion pump at home
All drugs administered on day 1 of each 14 day cycle.
FOLFOX regimen: FOLFOX (Oxaliplatin, Leucovorin, 5-Fluorouracil)
Liposomal Irinotecan: Liposomal Irinotecan | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | FOLFOX + Irinotecan |
|---|---|
| Age, Continuous | 65 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 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 | 24 Participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 28 |
| other Total, other adverse events | 28 / 28 |
| serious Total, serious adverse events | 15 / 28 |
Outcome results
Primary
Disease Control Rate (DCR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Disease Control Rate (DCR) = CR +PR+SD
Time frame: Up to 22 months
Population: In accordance with the Statistical Analysis Plan, the analysis population for the endpoint Disease Control Rate was defined as all participants who received at least one dose of trial drug and undergo at least one post-baseline disease assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX + Irinotecan | Disease Control Rate (DCR) | 73 Percentage of participants |
Secondary
Number of Participants With Adverse Events
Adverse events will be assessed to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Time frame: Up to 7 months
Population: The analysis population for Adverse Events was defined as all patients who received at least one dose of study treatment regardless of the dosage.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FOLFOX + Irinotecan | Number of Participants With Adverse Events | 28 Participants |
Secondary
Objective Response Rate (ORR) at 16 Weeks
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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Overall Response (OR) = CR + PR.
Time frame: 16 weeks
Population: All participants who have disease assessment at 16 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX + Irinotecan | Objective Response Rate (ORR) at 16 Weeks | 21 Percentage of participants |
Secondary
Objective Response Rate (ORR) at 24 Weeks
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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Overall Response (OR) = CR + PR.
Time frame: 24 weeks
Population: All participants who have disease assessment at 24 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX + Irinotecan | Objective Response Rate (ORR) at 24 Weeks | 25 Percentage of participants |
Secondary
Objective Response Rate (ORR) at 8 Weeks
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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Overall Response (OR) = CR + PR.
Time frame: 8 weeks
Population: All participants who have disease assessment at 8 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX + Irinotecan | Objective Response Rate (ORR) at 8 Weeks | 16 Percentage of participants |
Secondary
Overall Survival (OS)
Overall survival (OS) is defined as time from the first dose of study drug to date of death from any cause.
Time frame: Up to 31 months
Population: In accordance with the Statistical Analysis Plan, the analysis population for the endpoint Overall Survival was defined as all participants who received at least one dose of trial drug and either undergo at least one post-baseline disease assessment or die before any evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFOX + Irinotecan | Overall Survival (OS) | 18 Months |
Secondary
Progression-Free Survival (PFS)
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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Progression-free survival (PFS) as determined by the time interval from the date of first dose of study drug to first documented disease progression or death from any cause, whichever occurs first.
Time frame: Up to 22 months
Population: In accordance with the Statistical Analysis Plan, the analysis population for the endpoint Progression-Free Survival was defined as all participants who received at least one dose of trial drug and either undergo at least one post-baseline disease assessment or die before any evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFOX + Irinotecan | Progression-Free Survival (PFS) | 8.1 Months |
Secondary
Proportion of Subjects Able to Undergo Surgical Resection
Rate of resectability as determined by the proportion of subjects who undergo surgical resection of tumors.
Time frame: 12 months
Population: Out of 28 subjects, only 21 subjects had information for surgical resection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX + Irinotecan | Proportion of Subjects Able to Undergo Surgical Resection | 0.095 Proportion of participants |
Secondary
Quality of Life (QoL) Assessment: Global Health Status (EORTC QLQ-C30)
This secondary outcome measure evaluates overall quality of life using the Global Health Status scale from the EORTC QLQ-C30. Scores range from 0 to 100, with higher scores indicating better global health and quality of life. Mean (SD) scores are reported by assessment period, including only those participants who reached the defined time points (e.g., Cycle 9).
Time frame: Treatment Cycle 1 (14 days), Treatment Cycle 5 (70 days), Treatment Cycle 9 (126 days), Follow-Up (7 Months)
Population: All participants who reached the specified assessment time points (e.g., Cycle 9) were included in this outcome measure (Total 14 subjects). 13 out of these 14 subjects had information at treatment cycle 1, 12 out of these 14 subjects had information at treatment cycle 5, and 12 out of these 14 subjects had information at Follow-Up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FOLFOX + Irinotecan | Quality of Life (QoL) Assessment: Global Health Status (EORTC QLQ-C30) | Treatment Cycle 1 | 66.7 score on a scale | Standard Deviation 26.4 |
| FOLFOX + Irinotecan | Quality of Life (QoL) Assessment: Global Health Status (EORTC QLQ-C30) | Treatment Cycle 5 | 69.4 score on a scale | Standard Deviation 25.5 |
| FOLFOX + Irinotecan | Quality of Life (QoL) Assessment: Global Health Status (EORTC QLQ-C30) | Treatment Cycle 9 | 68.5 score on a scale | Standard Deviation 16.7 |
| FOLFOX + Irinotecan | Quality of Life (QoL) Assessment: Global Health Status (EORTC QLQ-C30) | Follow-Up | 76.4 score on a scale | Standard Deviation 17 |
Secondary
Response of Serum CA19-9 Levels
A CA 19-9 test measures the amount of a protein called CA19-9 (cancer antigen 19-9) in a sample of blood. Healthy people can have small amounts of CA 19-9 in their blood. High levels of CA 19-9 are often a sign of pancreatic cancer. Increasing CA 19-9 levels mean the tumor is growing, whether decreasing CA 19-9 levels may mean the tumor is shrinking. The Mean of the percentage change from baseline in serum CA19-9 levels associated with best confirmed response (PR, SD, PD) per RECIST 1.1 are reported in the outcome measure data table.
Time frame: Up to 7 months
Population: All participants who received at least one dose of trial drug, undergo at least one post-baseline disease assessment, and have post-baseline serum CA19-9 information.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FOLFOX + Irinotecan | Response of Serum CA19-9 Levels | Best response: PR | -69 Percentage Change from Baseline | Standard Deviation 37.41 |
| FOLFOX + Irinotecan | Response of Serum CA19-9 Levels | Best response: SD | -41 Percentage Change from Baseline | Standard Deviation 40.87 |
| FOLFOX + Irinotecan | Response of Serum CA19-9 Levels | Best response: PD | 31 Percentage Change from Baseline | Standard Deviation 8.04 |
Secondary
Stable Disease Rate (SDR) at 16 Weeks
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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Stable disease rate (SDR) as determined by the proportion of subjects with no progression of disease as defined by RECIST 1.1, at 16 weeks following initiation of FOLFOX-nal-IRI.
Time frame: 16 Weeks
Population: All participants who have disease assessment at 16 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX + Irinotecan | Stable Disease Rate (SDR) at 16 Weeks | 89 Percentage of participants |
Secondary
Stable Disease Rate (SDR) at 24 Weeks
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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Stable disease rate (SDR) as determined by the proportion of subjects with no progression of disease as defined by RECIST 1.1, at 24 weeks following initiation of FOLFOX-nal-IRI.
Time frame: 24 Weeks
Population: All participants who have disease assessment at 24 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX + Irinotecan | Stable Disease Rate (SDR) at 24 Weeks | 80 Percentage of participants |
Secondary
Stable Disease Rate (SDR) at 8 Weeks
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; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Stable disease rate (SDR) is determined by the proportion of subjects with no progression of disease as defined by RECIST 1.1, at 8 weeks following initiation of FOLFOX-nal-IRI.
Time frame: 8 Weeks
Population: All participants who have disease assessment at 8 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX + Irinotecan | Stable Disease Rate (SDR) at 8 Weeks | 84 Percentage of participants |