A Study of Nab-Paclitaxel and Gemcitabine With or Without Olaratumab (LY3012207) in Participants With Metastatic Pancreatic Cancer
- Conditions
- Metastatic Pancreatic Cancer
- Interventions
- Registration Number
- NCT03086369
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of this study is to determine the safety and efficacy of nab-paclitaxel and gemcitabine with or without olaratumab in the treatment of first-line metastatic pancreatic cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 184
- Histological or cytological diagnosis of adenocarcinoma of the exocrine pancreas that is metastatic (Stage IV) and not amenable to resection with curative intent.
- If present, clinically significant or symptomatic amounts of ascites should be drained prior to Day 1.
- Have had no prior systemic treatment for metastatic disease. Prior adjuvant or neo-adjuvant chemotherapy or radiochemotherapy (other than nab-paclitaxel) is allowed if completed ≥3 months prior to enrollment and no lingering toxicities are present.
- Prior radiation therapy for treatment of cancer is allowed to <25% of the bone marrow.
- Phase 2: archival tumor tissue or be willing to provide a pre-treatment biopsy.
- Measurable or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Discontinued all previous treatments for cancer ≥4 weeks prior.
- Adequate organ function.
- Life expectancy of at least 3 months.
- Serious concomitant systemic disorder.
- Have received first line treatment for metastatic pancreatic cancer.
- Received prior treatment with nab-paclitaxel.
- Have known central nervous system malignancy or metastasis.
- Current hematologic malignancies.
- Participated within the last 30 days in a clinical trial involving an investigational product.
- Women with a positive pregnancy test or lactating.
- Have endocrine pancreatic tumors or ampullary cancer.
- Currently enrolled in another clinical trial.
- Have a known additional malignancy that is progressing or required active treatment within the past 1 year.
- Known allergy to nab-paclitaxel or gemcitabine or any ingredient of study drug formulations.
- Are taking certain anti-coagulant medications such as warfarin and are unable to be switched to other similar medicines.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase1b: Olaratumab 20 mg/kg + Nab-paclitaxel + Gemcitabine Nab-paclitaxel Participants received intravenous infusions of olaratumab 20 mg/kg, nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase 2: Placebo + Nab-paclitaxel + Gemcitabine Nab-paclitaxel Participants received intravenous infusions of placebo, nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase 2: Olaratumab + Nab-paclitaxel + Gemcitabine Nab-paclitaxel Participants received intravenous infusions of olaratumab 20 mg/kg loading dose on days 1, 8, 15 of cycle 1 followed by 15 mg/kg on days 1, 8, 15 of all subsequent cycles, in combination with nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase1b: Olaratumab 15 mg/kg + Nab-paclitaxel + Gemcitabine Nab-paclitaxel Participants received intravenous (IV) infusions of olaratumab 15 milligrams per kilogram (mg/kg), nab-paclitaxel 125 milligrams per meter square (mg/m\^2) and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase 2: Placebo + Nab-paclitaxel + Gemcitabine Placebo Participants received intravenous infusions of placebo, nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase1b (cohort expansion): Olaratumab 20 mg/kg + Nab-paclitaxel + Gemcitabine Nab-paclitaxel Following a protocol amendment, "cohort expansion" arm was added in phase 1b with new participants enrolled to confirm the safety of the olaratumab 20 mg/kg dose prior to opening the Phase 2. Participants received intravenous infusions of olaratumab 20 mg/kg, nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase1b: Olaratumab 15 mg/kg + Nab-paclitaxel + Gemcitabine Olaratumab Participants received intravenous (IV) infusions of olaratumab 15 milligrams per kilogram (mg/kg), nab-paclitaxel 125 milligrams per meter square (mg/m\^2) and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase1b: Olaratumab 15 mg/kg + Nab-paclitaxel + Gemcitabine Gemcitabine Participants received intravenous (IV) infusions of olaratumab 15 milligrams per kilogram (mg/kg), nab-paclitaxel 125 milligrams per meter square (mg/m\^2) and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase1b: Olaratumab 20 mg/kg + Nab-paclitaxel + Gemcitabine Olaratumab Participants received intravenous infusions of olaratumab 20 mg/kg, nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase1b: Olaratumab 20 mg/kg + Nab-paclitaxel + Gemcitabine Gemcitabine Participants received intravenous infusions of olaratumab 20 mg/kg, nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase1b (cohort expansion): Olaratumab 20 mg/kg + Nab-paclitaxel + Gemcitabine Olaratumab Following a protocol amendment, "cohort expansion" arm was added in phase 1b with new participants enrolled to confirm the safety of the olaratumab 20 mg/kg dose prior to opening the Phase 2. Participants received intravenous infusions of olaratumab 20 mg/kg, nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase1b (cohort expansion): Olaratumab 20 mg/kg + Nab-paclitaxel + Gemcitabine Gemcitabine Following a protocol amendment, "cohort expansion" arm was added in phase 1b with new participants enrolled to confirm the safety of the olaratumab 20 mg/kg dose prior to opening the Phase 2. Participants received intravenous infusions of olaratumab 20 mg/kg, nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase 2: Olaratumab + Nab-paclitaxel + Gemcitabine Olaratumab Participants received intravenous infusions of olaratumab 20 mg/kg loading dose on days 1, 8, 15 of cycle 1 followed by 15 mg/kg on days 1, 8, 15 of all subsequent cycles, in combination with nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase 2: Olaratumab + Nab-paclitaxel + Gemcitabine Gemcitabine Participants received intravenous infusions of olaratumab 20 mg/kg loading dose on days 1, 8, 15 of cycle 1 followed by 15 mg/kg on days 1, 8, 15 of all subsequent cycles, in combination with nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met. Phase 2: Placebo + Nab-paclitaxel + Gemcitabine Gemcitabine Participants received intravenous infusions of placebo, nab-paclitaxel 125 mg/m\^2 and gemcitabine 1000 mg/m\^2 on days 1, 8, 15 of a 28-day cycle until disease progression or a criterion for discontinuation were met.
- Primary Outcome Measures
Name Time Method Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) Cycle 1 (Up to 28 days) A DLT is defined as an adverse event that is likely related to the study medication or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE version 4.03:
1. Any febrile neutropenia
2. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by clinically significant hemorrhage
3. Grade 4 neutropenia lasting 7 days or longer
4. Nonhematologic Grade ≥3 toxicity, except for toxicities such as nausea, vomiting, transient electrolyte abnormalities, diarrhea which can be controlled with optimal medical management within 48 hours; non-clinically significant, treatable, or reversible laboratory abnormalities including liver function tests, uric acid, electrolytes, etc.
5. Any other significant toxicity deemed to be dose-limiting (e.g., any toxicity that is possibly related to the study medication that requires the withdrawal of the participant from the study during Cycle 1).Phase 2: Overall Survival (OS) Baseline to Date of Death from Any Cause (Up To 29 Months) OS is defined as the time from the date of randomization to the date of death from any cause. If the participant is alive or lost to follow-up at the time of data analysis, OS data will be censored on the last date the participant is known to be alive. For any participant who has withdrawn consent for further follow-up of survival data, OS will be censored at the last date for which the participant consented to be followed for the study.
- Secondary Outcome Measures
Name Time Method Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L) Cycle 1 Day 1, Cycle 7 Day 1 The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of health status are each assessed with 5 response options (1=no problem, 2=slight, 3=moderate, 4=severe, and 5=extreme problem) and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status. Additionally, current health status was assessed on a visual analogue scale (VAS) ranging from 0 to 100 with a higher score representing better health status.
Phase 1b/2: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Olaratumab Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15 PK: Cmin of olaratumab
Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies Baseline through Follow-up (Up To 29 Months) Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies
Phase 1b: Overall Survival (OS) Baseline to Date of Death from Any Cause (Approximately 9 Months) OS is defined as the time from the date of randomization to the date of death from any cause. If the participant is alive or lost to follow-up at the time of data analysis, OS data will be censored on the last date the participant is known to be alive. For any participant who has withdrawn consent for further follow-up of survival data, OS will be censored at the last date for which the participant consented to be followed for the study.
Phase 2: Progression-Free Survival (PFS) Baseline to Disease Progression or Death (Up To 26 Months) PFS is defined as the time from randomization to the first date of radiologic disease progression (as defined by Response Evaluation Criteria In Solid Tumors, Version 1.1 \[RECIST v.1.1\]) or death due to any cause in the absence of progressive disease (PD). PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants who did not progress or are lost to follow-up were censored at the day of their last radiographic tumor assessment, if available, or date of randomization if no post-baseline radiographic assessment is available. If death or PD occurs after 2 or more consecutive missing radiographic visits, censoring will occur at the date of the last radiographic visit prior to the missed visits.
Phase 1b/2: Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) Baseline through Disease Progression or Death (Up To 26 Months) ORR is the best overall tumor response of CR or PR as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.
Phase 1b/2: Duration of Response (DoR) From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 19 Months) DoR is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence.
Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score" Baseline through Follow-up (Up To 21 Months) The mBPI-sf is a 11-item instrument used as a multiple-item measure of cancer pain intensity ranging from 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). Time to first worsening of the mBPI-sf "worst pain score" (TWP) was defined as the time from the date of randomization to the first date of either a "worst pain" score increase of greater than or equal to (≥) 2 points from baseline or an analgesic drug class increase of ≥1 level. If the participant has not worsened by either of these criteria, TWP was censored for analysis on the last date the mBPI-sf was administered.
Phase 2: Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Symptom Scales. Baseline through Follow-up (Up To 21 Months) The EORTC QLQ-C30 is a self-reported general cancer instrument consisting of 30 items covered by 1 of 3 dimensions: global health status/quality of life (2 items), functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, or financial impact). Time to first worsening of Symptom Burden was defined as the time from randomization to the first observation of worsening on symptom scales (i.e.,) increase of at least 10 points from baseline. For symptom scales, a linear transformation was used to obtain total score ranging from 0 to 100, a high score represents a high level of symptomatology or problems.
Trial Locations
- Locations (34)
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Sarah Cannon Research Institute SCRI
🇺🇸Nashville, Tennessee, United States
Tennessee Oncology PLLC
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
TRIO - Translational Research in Oncology-US, Inc.
🇺🇸Los Angeles, California, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
TGen Clinical Research Services at Scottsdale Healthcare
🇺🇸Scottsdale, Arizona, United States
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
St Jude Medical Center
🇺🇸Fullerton, California, United States
Smilow Cancer Hospital at Yale-New Haven
🇺🇸New Haven, Connecticut, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
H Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Fort Wayne Oncology & Hematology
🇺🇸Fort Wayne, Indiana, United States
Monter Cancer Center
🇺🇸Lake Success, New York, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Univ of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Sanford Research/USD
🇺🇸Sioux Falls, South Dakota, United States
University of Utah School of Medicine
🇺🇸Salt Lake City, Utah, United States
Chattanooga Oncology Hematology Associates
🇺🇸Chattanooga, Tennessee, United States
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Cancer Center of Santa Barbara with Sansum Clinic
🇺🇸Santa Barbara, California, United States
University of Wisconsin-Madison Hospital and Health Clinic
🇺🇸Madison, Wisconsin, United States
Central Coast Medical Oncology Corporation
🇺🇸Santa Maria, California, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialists and Research Institute
🇺🇸Saint Petersburg, Florida, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Charité Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States