A Phase 1b (Open-Label) / Phase 2 (Randomized, Double-Blinded) Study Evaluating Nab-Paclitaxel and Gemcitabine With or Without Olaratumab in the Treatment of First-Line Metastatic Pancreatic Cancer
Overview
- Phase
- Phase 1
- Intervention
- Olaratumab
- Conditions
- Metastatic Pancreatic Cancer
- Sponsor
- Eli Lilly and Company
- Enrollment
- 184
- Locations
- 34
- Primary Endpoint
- Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •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
- •Discontinued all previous treatments for cancer ≥4 weeks prior.
- •Adequate organ function.
- •Life expectancy of at least 3 months.
Exclusion Criteria
- •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.
Arms & Interventions
Phase1b: Olaratumab 15 mg/kg + Nab-paclitaxel + 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.
Intervention: Olaratumab
Phase1b: Olaratumab 15 mg/kg + Nab-paclitaxel + 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.
Intervention: Nab-paclitaxel
Phase1b: Olaratumab 15 mg/kg + Nab-paclitaxel + 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.
Intervention: Gemcitabine
Phase1b: Olaratumab 20 mg/kg + Nab-paclitaxel + 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.
Intervention: Olaratumab
Phase1b: Olaratumab 20 mg/kg + Nab-paclitaxel + 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.
Intervention: Nab-paclitaxel
Phase1b: Olaratumab 20 mg/kg + Nab-paclitaxel + 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.
Intervention: Gemcitabine
Phase1b (cohort expansion): Olaratumab 20 mg/kg + Nab-paclitaxel + 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.
Intervention: Olaratumab
Phase1b (cohort expansion): Olaratumab 20 mg/kg + Nab-paclitaxel + 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.
Intervention: Nab-paclitaxel
Phase1b (cohort expansion): Olaratumab 20 mg/kg + Nab-paclitaxel + 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.
Intervention: Gemcitabine
Phase 2: Olaratumab + Nab-paclitaxel + 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.
Intervention: Olaratumab
Phase 2: Olaratumab + Nab-paclitaxel + 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.
Intervention: Nab-paclitaxel
Phase 2: Olaratumab + Nab-paclitaxel + 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.
Intervention: Gemcitabine
Phase 2: Placebo + Nab-paclitaxel + 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.
Intervention: Nab-paclitaxel
Phase 2: Placebo + Nab-paclitaxel + 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.
Intervention: Gemcitabine
Phase 2: Placebo + Nab-paclitaxel + 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.
Intervention: Placebo
Outcomes
Primary Outcomes
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: 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)
Time Frame: 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 Outcomes
- Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)(Cycle 1 Day 1, Cycle 7 Day 1)
- 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)
- Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies(Baseline through Follow-up (Up To 29 Months))
- Phase 1b: Overall Survival (OS)(Baseline to Date of Death from Any Cause (Approximately 9 Months))
- Phase 2: Progression-Free Survival (PFS)(Baseline to Disease Progression or Death (Up To 26 Months))
- 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))
- 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))
- 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))
- 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))