Conditions

Neoplasms Neoplasm Metastasis Pancreatic Cancer

Keywords

NeoplasmsNeoplasm MetastasisPancreatic Cancer

Outcome Measures

Primary Outcomes (2)

Phase 1b: Recommended Phase 2 Dose
The recommended Phase 2 dose was the highest dose where less than 1/3 of participants experienced dose limiting toxicities (DLTs). The recommended dose was determined based on a review of overall toxicity, dose reductions, omissions, and pharmacokinetic information from Phase 1b.
Time of first phase 1b dose until time of last phase 1b dose (up to 1 year)
Phase 2: Overall Survival (OS)
Overall survival is defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact.
Baseline to date of death from any cause (up to 2 years)

Secondary Outcomes (10)

Phase 1b: Pharmacokinetics: Area Under the Concentration-Time Curve at Steady State From Time Zero to 24 Hours (AUC[0-24], ss) and Time Zero to Infinity (AUC[0-∞], ss)
Cycle 1 Days 14 (predose; 0.5, 2, 3, and 6 hours post dose), 24h (Days 15) and 48h (Days 16)
Phase 1b: Pharmacokinetics: Maximum Plasma Drug Concentration at Steady State (Cmax,ss)
Cycle 1 Days 14 (predose; 0.5, 2, 3, and 6 hours post dose), 24h (Days 15) and 48h (Days 16)
Phase 1b: Number of Participants With Tumor Response
Baseline to end of Phase 1b (up to 1 year)
Phase 2: Progression Free Survival (PFS)
Baseline to first date of progressive disease or death due to any cause (up to 2 years)
Phase 2: Percentage Change From Baseline in Tumor Size (CTS)
Baseline, end of Cycle 2 (up to 56 days)
+5 more secondary outcomes

Study Arms (5)

Phase 1b: 80 mg Galunisertib + Gemcitabine

EXPERIMENTAL

Cohort 1: 40 mg Galunisertib was administered orally twice daily (BID) for 14 days followed by 14 days of rest (28 day cycle). Gemcitabine at a dose of 1000 mg/m\^2 was administered intravenously once per week for 7 weeks followed by 1 week of rest and then once per week for 3 weeks of every 4 weeks.

Drug: GalunisertibDrug: Gemcitabine

Phase 1b: 160 mg Galunisertib + Gemcitabine

EXPERIMENTAL

Cohort 2: 80 mg Galunisertib was administered orally twice daily for 14 days followed by 14 days of rest (28 day cycle). Gemcitabine at a dose of 1000 mg/m\^2 was administered intravenously once per week for 7 weeks followed by 1 week of rest and then once per week for 3 weeks of every 4 weeks.

Drug: GalunisertibDrug: Gemcitabine

Phase 1b: 300 mg Galunisertib + Gemcitabine

EXPERIMENTAL

Cohort 3: 150 mg Galunisertib was administered orally twice daily for 14 days followed by 14 days of rest (28 day cycle). Gemcitabine at a dose of 1000 mg/m\^2 was administered intravenously once per week for 7 weeks followed by 1 week of rest and then once per week for 3 weeks of every 4 weeks.

Drug: GalunisertibDrug: Gemcitabine

Phase 2: Recommended dose of Galunisertib + Gemcitabine

EXPERIMENTAL

Galunisertib recommended dose (300 mg) determined from phase 1, administered orally twice daily for 14 days followed by 14 days of rest (28 day cycle). Gemcitabine at a dose of 1000 mg/m\^2 was administered intravenously once per week for 7 weeks followed by 1 week of rest and then once per week for 3 weeks of every 4 weeks.

Drug: GalunisertibDrug: Gemcitabine

Phase 2: Placebo + Gemcitabine

EXPERIMENTAL

Placebo administered orally twice daily for 14 days followed 14 days of rest (28 day cycle). Gemcitabine at a dose of 1000 mg/m\^2 was administered intravenously once per week for 7 weeks followed by 1 week of rest and then once per week for 3 weeks of every 4 weeks.

Drug: GemcitabineDrug: Placebo

Interventions

GalunisertibDRUG

Administered orally

Also known as: LY2157299

Phase 1b: 160 mg Galunisertib + GemcitabinePhase 1b: 300 mg Galunisertib + GemcitabinePhase 1b: 80 mg Galunisertib + GemcitabinePhase 2: Recommended dose of Galunisertib + Gemcitabine

GemcitabineDRUG

Administered intravenously

Also known as: Gemzar, LY188011

Phase 1b: 160 mg Galunisertib + GemcitabinePhase 1b: 300 mg Galunisertib + GemcitabinePhase 1b: 80 mg Galunisertib + GemcitabinePhase 2: Placebo + GemcitabinePhase 2: Recommended dose of Galunisertib + Gemcitabine

PlaceboDRUG

Administered orally

Phase 2: Placebo + Gemcitabine

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

For Phase 1b:
Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease; that is refractory to standard therapy and/or therapies known to provide clinical benefit or for which no standard therapy exists; and/or in which gemcitabine therapy at the proposed doses and schedule would be considered appropriate treatment for the metastatic disease (eg, pancreatic cancer)
Patients may have received prior chemotherapy, radiotherapy, cancer-related hormone therapy, or other investigational therapy as treatment. There is no limit in the number of previous lines of therapy.
For Phase 1b and Phase 2:
Have measurable disease or non-measurable disease, defined according to Response Evaluation Criteria In Solid Tumors (RECIST)
Have given written informed consent prior to any study-specific procedures
Have adequate organ function including: Hematologic: absolute neutrophil count (ANC) greater than or equal to 1.5 x 10\^9/L, platelets greater than or equal to 100 x 10\^9/L, and hemoglobin greater than or equal to 9 g/dL. Hepatic: bilirubin less than or equal to 1.5 times upper limit of normal (ULN), and alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT)less than or equal to 2.5 times ULN. If the liver has tumor involvement, AST less than or equal to 5 times ULN and ALT less than or equal to 5 times ULN are acceptable. Patients may have endoscopic or radiologic stenting to treat biliary obstructions. If so, then bilirubin must return to less than or equal to 1.5 times ULN and ALP, AST, and ALT to less than or equal to 5 times ULN prior to enrollment. Renal: serum creatinine within normal limits, less than or equal to 1.5 times ULN.
Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
Patients must have recovered from any Grade 3/4 toxicities of previous therapies
Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
Prior radiation therapy for treatment of cancer is allowed to \<25% of the bone marrow, and patients must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study entry.
Male and female patients with reproductive potential must use an approved contraceptive method during and for 3 months after discontinuation of study treatment. Women of childbearing potential must have a negative beta-human chorionic gonadotropin (B-HCG) pregnancy test documented within 14 days prior to treatment. If condoms are used as a barrier contraceptive, a spermicidal agent should be added to ensure that pregnancy does not occur. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
For Phase 2:
Have histological or cytological diagnosis of adenocarcinoma of the pancreas that is locally advanced (Stage II, III) or metastatic (Stage IV) and not amenable to resection with curative intent. Patients with previous radical surgery for pancreatic cancer are eligible after progression is documented. If they received adjuvant chemotherapy or chemoradiotherapy with gemcitabine, they can be enrolled if the treatment was completed 3 months before or longer
Tumor tissue or unstained slides are available from original biopsy or resection or other tumor biopsies
+1 more criteria

You may not qualify if:

Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or unapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Have moderate or severe cardiac disease:
Myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension
Major abnormalities documented by echocardiography with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction (LVEF) \<50%, evaluation based on the institutional lower limit of normal)
Predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by CT scan or MRI with contrast)
Are unable to swallow tablets or capsules
Are pregnant or breastfeeding
Have any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ), unless in complete remission and off of all therapy for that disease for a minimum of 3 years
Have active infection that would interfere with the study objectives or influence study compliance
Phase 2 only: Endocrine pancreatic tumors or ampullary cancer
Patients with acute or chronic leukemia or with any other disease likely to have a significant bone marrow infiltration (screening not required)
Have previously completed or withdrawn from this study or any other study investigating galunisertib or any other TGF-ß inhibitor
Have known allergy to galunisertib or gemcitabine or any ingredient of galunisertib or gemcitabine formulations

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Eli Lilly and Companylead

Study Sites (24)

Florida Hospital Tampa HPG and Foregut Surgery

Tampa, Florida, 33613, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location