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A Study of Nab-Paclitaxel and Gemcitabine With or Without Olaratumab (LY3012207) in Participants With Metastatic Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03086369
Recruitment Status : Completed
First Posted : March 22, 2017
Results First Posted : January 11, 2022
Last Update Posted : June 28, 2022
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Cancer Drug: Olaratumab Drug: Nab-paclitaxel Drug: Gemcitabine Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 184 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 22, 2017
Actual Primary Completion Date : January 5, 2021
Actual Study Completion Date : June 17, 2021


Arm Intervention/treatment
Experimental: 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.
Drug: Olaratumab
Administered IV
Other Name: LY3012207

Drug: Nab-paclitaxel
Administered IV

Drug: Gemcitabine
Administered IV

Experimental: 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.
Drug: Olaratumab
Administered IV
Other Name: LY3012207

Drug: Nab-paclitaxel
Administered IV

Drug: Gemcitabine
Administered IV

Experimental: 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.
Drug: Olaratumab
Administered IV
Other Name: LY3012207

Drug: Nab-paclitaxel
Administered IV

Drug: Gemcitabine
Administered IV

Experimental: 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.
Drug: Olaratumab
Administered IV
Other Name: LY3012207

Drug: Nab-paclitaxel
Administered IV

Drug: Gemcitabine
Administered IV

Placebo Comparator: 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.
Drug: Nab-paclitaxel
Administered IV

Drug: Gemcitabine
Administered IV

Drug: Placebo
Administered IV




Primary Outcome Measures :
  1. 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).

  2. 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 Outcome Measures :
  1. Phase 1b/2: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Olaratumab [ Time Frame: 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

  2. Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies [ Time Frame: Baseline through Follow-up (Up To 29 Months) ]
    Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies

  3. Phase 1b: Overall Survival (OS) [ Time Frame: 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.

  4. Phase 2: Progression-Free Survival (PFS) [ Time Frame: 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.

  5. Phase 1b/2: Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) [ Time Frame: 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.

  6. Phase 1b/2: Duration of Response (DoR) [ Time Frame: 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.

  7. Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score" [ Time Frame: 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.

  8. 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. [ Time Frame: 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.

  9. Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L) [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03086369


Locations
Show Show 34 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] March 20, 2019
Statistical Analysis Plan  [PDF] April 3, 2020

Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03086369    
Other Study ID Numbers: 15844
I5B-MC-JGDP ( Other Identifier: Eli Lilly and Company )
2016-001099-31 ( EudraCT Number )
First Posted: March 22, 2017    Key Record Dates
Results First Posted: January 11, 2022
Last Update Posted: June 28, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Paclitaxel
Olaratumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs