First-Line Metastatic Pancreatic Cancer MedDRA version: 20.0 Level: PT Classification code 10073364 Term: Ductal adenocarcinoma of pancreas System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Lartruvo
Product Name: olaratumab
Product Code: LY3012207
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: olaratumab
CAS Number: 1024603-93-7
Other descriptive name: OLARAT
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] have histological or cytological diagnosis of adenocarcinoma of the exocrine pancreas that is metastatic (Stage IV) and not amenable to resection with curative intent and be patients for whom nab-paclitaxel-gemcitabine therapy is considered by the investigator to be an appropriate treatment. Patients with previous radical surgery for pancreatic cancer are eligible after progression is documented. [2] if present, clinically significant or symptomatic amounts of ascites should be drained prior to Day 1 [3] have sufficient available material from an archived formalin-fixed paraffinembedded (FFPE) tumor tissue for biomarker-related studies. If such tissue is not available, a newly obtained core or excisional biopsy of a tumor lesion must be performed in the Phase 2 portion of the study. [4] The patient has measurable or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1, Eisenhauer et al. 2009). Tumors within a previously irradiated field will be designated as “nontarget” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiotherapy. [5] have had no prior systemic treatment for metastatic disease. Prior adjuvant or neo-adjuvant chemotherapy or radiochemotherapy use of gemcitabine monotherapy is allowed if completed = 3 months prior to enrollment. Prior treatment with 5-Fluorouracil (5-FU) administered as a radiation sensitizer in the adjuvant setting is allowed, if completed =3 months prior to enrollment and no lingering toxicities are present. [6] prior radiation therapy for treatment of cancer is allowed to <25% of the bone marrow (Cristy and Eckerman 1987). Patients must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiotherapy must be completed =3 months prior to study entry. [7] have a performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) scale (Oken et al. 1982) [8] have discontinued all previous treatments for cancer and recovered from the acute effects of therapy. Patients must have discontinued from previous treatments (radiotherapy/ [9] have adequate organ function [10] are at least 18 years old at the time of screening/randomization [11] If male, the patient is sterile (including vasectomy) or agrees to use an effective method of birth control. Refer to Appendix 1 for definitions of effective method [12] If female: o is not of childbearing potential due to surgical sterilization confirmed by medical history (at least 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) or menopause o is of childbearing potential, has a negative serum or urine pregnancy test within 72 hours prior to the first dose of study treatment, agrees to use a highly effective method of birth control during the study and for up to 120 days following the last dose of the study treatment, and is not breastfeeding. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Refer to Appendix 1 for definitions of effective method of contraception and highly effective method of contraception. [13] have given written informed consent/assent prior to any study-specific procedures [14] has a life expectancy of at least 3 months in the opinion of the investigators Are the trial subjects under 18? no Number of
Exclusion criteria
Exclusion criteria: [15] have received first line treatment for metastatic pancreatic cancer. [16] have received prior treatment with FOLFOX or FOLFIRINOX. [17] have a serious concomitant systemic disorder (for example, active infection including human immunodeficiency virus, or cardiac disease) or other condition that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol [18] have known central nervous system (CNS) malignancy or metastasis (screening not required) [19] have current hematologic malignancies, acute or chronic leukemia [20] have participated within the last 30 days in a clinical trial involving an investigational product. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed. [21] are women with a positive pregnancy test or who are lactating [22] have endocrine pancreatic tumors or ampullary cancer [23] are currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study [24] have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ), unless in complete remission and off all therapy for that disease for a minimum of 1 year [25] have known allergy to nab-paclitaxel, gemcitabine, or any ingredient of olaratumab, nab-paclitaxel, or gemcitabine formulations
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase Ib: To determine a recommended Phase 2 dose of olaratumab in combination with nab-paclitaxel and gemcitabine Phase II: To compare the efficacy of olaratumab plus nab-paclitaxel and gemcitabine with placebo plus gemcitabine and nab-paclitaxel;Secondary Objective: Phase 1b ? to characterize the safety and toxicity profile of olaratumab plus nab-paclitaxel and gemcitabine ? to evaluate the PK and immunogenicity of olaratumab plus nab-paclitaxel and gemcitabine ? to document the antitumor activity observed with olaratumab plus nab-paclitaxel and gemcitabine Phase 2 ? to assess time-to-event variables ? to document the antitumor activity observed with olaratumab plus nab-paclitaxel and gemcitabine ? to assess PROs: pain, HRQoL, and health status ? to determine safety and tolerability of olaratumab in combination with nab-paclitaxel and gemcitabine ? to assess the PK and immunogenicity;Primary end point(s): Phase 1b ? DLTs ? Safety (including but not limited to) TEAEs, SAEs, and clinical laboratory abnormalities Phase 2 ? OS;Timepoint(s) of evaluation of this end point: DLT-evaluable Population: The DLT-evaluable population will include all enrolled patients who complete Cycle 1 or discontinue due to a DLT prior to completing Cycle 1 treatment. Safety population: All enrolled patients who receive any quantity of study treatment, regardless of their eligibility for the study, will be included in the safety analysis. Safety evaluation will be performed based on the actual initial therapy a patient has received, regardless of any other cohort to which he or she was assigned. The primary analysis of OS will be performed when a minimum of 113 OS events have been observed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1b ? Safety monitoring, including TEAEs, SAE, and deaths ? Minimum serum/plasma concentration of olaratumab plus nab-paclitaxel and gemcitabine ? OS, PFS, ORR, and DoR Phase 2 ? PFS, DoR ? ORR ? mBPI-sf, EORTC-QLQ-C30, and EQ-5D-5L ? TEAEs, AESI, SAEs, clinical laboratory tests, vital signs, physical examinations, hospitalization, and deaths ? Minimum serum/plasma concentration of olaratumab plus nab-paclitaxel and gemcitabine;Timepoint(s) of evaluation of this end point: An interim analysis that includes both safety and efficacy will be conducted. The analysis will occur after at least 70 OS events have been observed among Phase 2 patients. The interim analysis will not be used for purposes of formally testing any efficacy hypotheses, but descriptive efficacy results will be considered in order to decide whether or not a separate Phase 3 trial evaluating olaratumab in combination with nab-paclitaxel and gemcitabine should be initiated. | — |
Countries
Germany, Italy, Spain, United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly
Outcome results
None listed