| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Pancreatic Ductal Adenocarcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| A type of pancreatic cancer that originated in the cells of tubes or ducts in the pancreas, and has spread beyond the pancreas |
|
| 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 | LLT |
| E.1.2 | Classification code | 10033599 |
| E.1.2 | Term | Pancreatic adenocarcinoma metastatic |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
STAGE 1:
•To evaluate disease control rate of the abemaciclib treatment arms versus the standard-of-care arm (gemcitabine or capecitabine)
STAGE 2
•To evaluate progression-free survival of the abemaciclib treatment arms versus the standard of care arm (gemcitabine or capecitabine) |
|
| E.2.2 | Secondary objectives of the trial |
STAGE 1:
To evaluate objective response rate of the abemaciclib treatment arms versus the SOC arm
Evaluate safety and tolerability of the abemaciclib treatment arms
PK of abemaciclib and its metabolites, LY3023414,
and galunisertib
Exposure-response for abemaciclib, LY3023414, and galunisertib
STAGE 2
To evaluate DCR of the abemaciclib treatment arms versus the SOC arm
To evaluate CBR of the abemaciclib treatment arms versus the SOC arm
To evaluate objective response rate of the abemaciclib treatment arms versus the SOC arm
To evaluate duration of response of the abemaciclib treatment arms versus the SOC arm
To evaluate OS of the abemaciclib treatment arms versus the SOC arm
Evaluate the kinetics of (CA) 19-9
Safety and tolerability
To evaluate pain and symptom burden of the
abemaciclib treatment arms by best response group
(partial response, stable disease, or progressive disease) versus the SOC arm
PK of abemaciclib ,metabolites, LY3023414,
and galunasertib
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] have cytologically or histologically confirmed diagnosis of ductal adenocarcinoma of the pancreas.
[2] have metastatic disease with documented disease progression following previous treatment with at least one, but no more than 2 prior therapies for metastatic disease, with at least one of the prior therapies having been either gemcitabine-based or fluoropyrimidine-based therapy. Neoadjuvant and/or adjuvant therapies for localized resectable or unresectable PDAC each count as a line of therapy if multiagent chemotherapy regimens were administered (and neoadjuvant regimen was different than adjuvant regimen) and if the patient progressed with metastatic disease during treatment or within 6 months of completion of (neo)adjuvant therapy.
[3] have the presence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
[4] have a performance status (PS) of 0 to 1 on the ECOG scale
[5] is a patient for whom treatment with monotherapy chemotherapy such as gemcitabine or capecitabine is a reasonable choice.
[6] have discontinued all previous treatments for cancer (including cytotoxic chemotherapy, molecularly targeted therapy, radiotherapy, immunotherapy, and investigational therapy) for at least 14 days prior to receiving the initial dose of study treatment, and recovered from the acute effects of therapy (treatment-related toxicity resolved to baseline) except for residual alopecia or peripheral neuropathy.
[7} have adequate organ functions
[8] are at least 18 years old at the time of screening or of an age acceptable according to local regulations, whichever is older.
[9] men must be sterile or agree to use an effective method of contraception or a highly effective method of contraception during the study and for at least 6 months following the last dose of study drug.
[10] women of child-bearing potential must:
a. have a negative serum pregnancy test within 7 days prior to study treatment initiation, and
b. agree to use a highly effective method of contraception during the study and for at least 6 months following the last dose of study drug.
[11] have given written informed consent prior to any study-specific procedures.
[12] are able to swallow capsules and tablets.
[13] are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures. |
|
| E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria:
[14] have a serious concomitant systemic disorder or preexisting condition (for example, active infection including human immunodeficiency virus, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis) that, in the opinion of the investigator, would compromise the patient’s safety or ability to adhere to the protocol.
[15] have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhytmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
Exception: Patients with controlled atrial fibrillation for ≥ 30 days prior to study treatment initiation are eligible.
[16] Deleted Criterion.
[17] have insulin-dependent diabetes mellitus. Patients with type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetics as documented by hemoglobin A1c (HbA1c) <7%.
[18] have symptomatic central nervous system metastasis. Screening of asymptomatic patients is not required for enrollment.Screening is not required for enrollment.
[19] have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 2 years.
[20] have had major surgery within 7 days prior to initiation of study drug to allow for postoperative healing of the surgical wound and site(s).
[21] 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. If a patient is currently enrolled in a clinical trial involving nonapproved use of a device, then agreement with the investigator and Lilly clinical research physician (CRP) is required to establish eligibility.
[22] have received treatment with a drug that has not received regulatory approval for any indication within 14 days prior to receiving the initial dose of study treatment.
[23] have previously received treatment with any CDK4 and 6 inhibitor, TGF-inhibitor, or PI3K and/or mTOR inhibitor or have a known hypersensitivity to any component of the investigational products in this study.
[24] have a known hypersensitivity to investigator's choice of standard of care (gemcitabine or capecitabine) in anticipation that the patient may be randomized to Arm D.
[25] are pregnant or breastfeeding |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately 16 weeks following the last patient to enter treatment in stage 1. For Stage 1 and Stage 2, tumor scans will occur approximately every 8 weeks. Initial evaluations will compare disease control rate (DCR; complete response [CR]+partial response [PR]+stable disease [SD]).
The primary analysis of Stage 2 will be conducted when at least 120 total PFS events have occurred for the combination of each individual abemaciclib-containing arm and the standard-of-care arm, or all planned
patients have been enrolled in Stage 2, whichever comes later. |
|
| E.5.2 | Secondary end point(s) |
STAGE 1
ORR
Evaluate safety and tolerability of the abemaciclibtreatment arms
Exposure of abemaciclib, LY3023414, and galunasertib
STAGE 2
DCR, CBR, ORR, DOR, OS
safety endpoints evaluated will include but are not limited to the following:
TEAEs and SAEs
Clinical laboratory tests and vital signs
modified Brief Pain Inventory short form (mBPI-sf)
and the European Organization for Research and
Treatment of Cancer Quality of Life Questionnaire-
Core 30 (EORTC QLQ-C30)
Exposure of abemaciclib, LY3023414, and
galunasertib
Drug exposure and efficacy outcomes such as
objective response rate or progression-free survival
and safety outcomes such as neutropenia and
diarrhea |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Approximately 16 weeks following the last patient to enter treatment in stage 1. For Stage 1 and Stage 2, tumor scans will occur approximately every 8 weeks. Initial evaluations will compare disease control rate (DCR; complete response [CR]+partial response [PR]+stable disease [SD]).
The primary analysis of Stage 2 will be conducted when at least 120 total PFS events have occurred for the combination of each individual abemaciclib-containing arm and the standard-of-care arm, or all planned
patients have been enrolled in Stage 2, whichever comes later. |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| 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 |
| Argentina |
| Australia |
| Belgium |
| Brazil |
| France |
| Hungary |
| Israel |
| Spain |
| Taiwan |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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