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

Lilly

Status and phase: Completed; Phase 2; Phase 1

Conditions: Metastatic Pancreatic Cancer

Treatments: Drug: Gemcitabine; Drug: Nab-paclitaxel; Drug: Placebo; Drug: Olaratumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03086369

15844

2016-001099-31 (EudraCT Number)

I5B-MC-JGDP (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 184 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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184 participants in 5 patient groups, including a placebo group

Phase1b: Olaratumab 15 mg/kg + Nab-paclitaxel + Gemcitabine

Experimental group

Description:

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.

Treatment:

Drug: Olaratumab

Drug: Gemcitabine

Drug: Nab-paclitaxel

Phase1b: Olaratumab 20 mg/kg + Nab-paclitaxel + Gemcitabine

Experimental group

Description:

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.

Treatment:

Drug: Olaratumab

Drug: Gemcitabine

Drug: Nab-paclitaxel

Phase1b (cohort expansion): Olaratumab 20 mg/kg + Nab-paclitaxel + Gemcitabine

Experimental group

Description:

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.

Treatment:

Drug: Olaratumab

Drug: Gemcitabine

Drug: Nab-paclitaxel

Phase 2: Olaratumab + Nab-paclitaxel + Gemcitabine

Experimental group

Description:

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.

Treatment:

Drug: Olaratumab

Drug: Gemcitabine

Drug: Nab-paclitaxel

Phase 2: Placebo + Nab-paclitaxel + Gemcitabine

Placebo Comparator group

Description:

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.

Treatment:

Drug: Gemcitabine

Drug: Placebo

Drug: Nab-paclitaxel