BYL719 in Combination With Gemcitabine and (Nab)-Paclitaxel in Locally Advanced and Metastatic Pancreatic Cancer

NCT02155088 | Completed Phase 1 FDA Drug

• 1 other identifier: MCC-17815
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to see primarily if BYL719 is safe to be given to patients in combination with gemcitabine and nab-paclitaxel. Gemcitabine and nab-paclitaxel is an FDA-approved regimen to treat pancreatic cancer. Secondary goals will be to find out the effect on tumor of this new drug combination of BYL719, gemcitabine and nab-paclitaxel. In the first part of the study, different doses of BYL719 will be tested. In the second part of the study, all patients will be started at the same dose of BYL719.

Conditions

Pancreatic Cancer

Keywords

Locally Advanced; Metastatic; Recurrent; Pancreas

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  The MTD is defined as the highest dose level at which one or none of 6 patients experience a Dose Limiting Toxicity (DLT).

  Up to 4 months per participant

Secondary Outcomes (3)

• Overall Response Rate (ORR)

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

• Progression-Free Survival (PFS)

  Up to 3 years

Study Arms (1)

Combination Therapy: BYL719, Gemcitabine, (Nab)-Paciltaxel

EXPERIMENTAL

Dose escalation, followed by expansion, of BYL719 in combination with Gemcitabine and (Nab)-Paclitaxel. BYL719: once daily. Gemcitabine: Days 1,8, 15 of 28-day cycle. (Nab)-Paclitaxel: Days 1,8, 15 of 28-day cycle.

Drug: BYL719; Drug: Gemcitabine; Drug: (nab)-paclitaxel

Interventions

BYL719 DRUG

Dose escalation beginning at 250 mg/day

Also known as: a-specific P13K inhibitor

Combination Therapy: BYL719, Gemcitabine, (Nab)-Paciltaxel

Gemcitabine DRUG

Dose escalation beginning at 800 mg/m\^2

Also known as: Gemzar

Combination Therapy: BYL719, Gemcitabine, (Nab)-Paciltaxel

(nab)-paclitaxel DRUG

125 mg/m\^2 dose

Also known as: Abraxane

Combination Therapy: BYL719, Gemcitabine, (Nab)-Paciltaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is able to swallow and retain oral medication
• Histologically documented diagnosis of pancreatic adenocarcinoma.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Required baseline laboratory status according to protocol document

You may not qualify if:

• Prior sensitivity or intolerance to PI3K inhibitors
• Potential participants with central nervous system (CNS) involvement may participate if the patient is: \>/= 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment; Clinically stable with respect to the CNS tumor at the time of screening; Not receiving steroid therapy.
• Prior treatment with any cytotoxic chemotherapy for treatment of pancreatic cancer except as an adjuvant therapy. Should not have received gemcitabine within 6 months of starting the study treatment. 5-Fluorouracil or radiation treatment should be received more than 4 weeks prior to receiving the study drug.
• Potential participants who have received radiotherapy ≤ 4 weeks prior to starting study drugs, with exception of palliative radiotherapy, who have not recovered from side effects of such therapy to baseline or Grade ≤ 1 and/or from whom ≥ 30% of the bone marrow was irradiated.
• Potential participants who have undergone major surgery ≤ 4 weeks prior to starting study treatment or who have not recovered from side effects of such procedure.
• Have received investigation agent within 30 days prior to enrollment
• Clinically significant cardiac disease or impaired cardiac function
• QT interval adjusted according to Fredericia (QTcF) \> 480 msec on screening ECG
• Potential participants with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting plasma glucose (FPG)\> 140 mg/dL or history of documented steroid-induced diabetes mellitus.
• Any other condition that would, in the Investigator's judgment, preclude participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g. infection/inflammation, intestinal obstruction, unable to swallow oral medication, social/psychological complications.
• Impaired GI function or GI disease that may significantly alter the absorption of oral BYL719 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus \[HBV\]-DNA and/or positive HbsAg, quantifiable hepatitis C virus \[HCV\]-RNA).
• Known positive serology for human immunodeficiency virus (HIV)
• Known severely impaired lung function (spirometry and diffusing capacity of lung for carbon monoxide\[DLCO\] 50% or less of normal and O2 saturation 88% or less at rest on room air).
• Currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Novartis: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasm Metastasis; Recurrence

Interventions

Alpelisib; Gemcitabine; Taxes; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Richard Kim, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2014
• First Posted: June 4, 2014
• Study Start: October 30, 2014
• Primary Completion: December 1, 2016
• Study Completion: January 31, 2020
• Last Updated: April 8, 2021

Record last verified: 2021-04

Locations

US (1)