E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
First-Line Metastatic Pancreatic Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Pancreatic cancer that has spread to other areas of the body. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073364 |
E.1.2 | Term | Ductal adenocarcinoma of pancreas |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
|
E.2.2 | Secondary objectives of the trial |
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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1b
DLTs
Safety (including but not limited to) TEAEs, SAEs,
and clinical laboratory abnormalities
Phase 2
OS |
|
E.5.1.1 | 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. |
|
E.5.2 | 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 |
|
E.5.2.1 | 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. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Phase 1b of the study is open label. Phase 2 is double-blind |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
Italy |
Spain |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |