Enzalutamide in Combination With Gemcitabine and Nab-Paclitaxel for the Treatment of Advanced Pancreatic Cancer

NCT02138383 | Completed Phase 1

• 1 other identifier: MCC-17696
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to find out the dose of enzalutamide that can be safely given with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer. Researchers also want to find out the side effects of these drugs when given together. This study will help in finding out the effect on tumor of the combination of enzalutamide, gemcitabine and nab-paclitaxel. In the first part of the study, different doses of enzalutamide will be tested. In the second part of the study, all patients will be started at the same dose of enzalutamide.

Conditions

Pancreatic Cancer

Keywords

advanced pancreatic cancer; pancreas; malignant neoplasm; endocrine system

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  To determine the maximally tolerated dose (MTD) of enzalutamide in combination with gemcitabine and nab-paclitaxel in advanced pancreatic cancer.

  Up to 18 months

Study Arms (1)

Dose Escalation and Dose Expansion

EXPERIMENTAL

Dose Escalation: To find the dose of enzalutamide that can be safely given with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer. Dose Expansion: To find the effect on tumor of the combination of enzalutamide, gemcitabine and nab-paclitaxel.

Drug: Enzalutamide; Drug: Gemcitabine; Drug: Nab-paclitaxel

Interventions

Enzalutamide DRUG

The starting dose of enzalutamide will be 80 mg (Level 1) daily, taken orally. The dose escalation schedule is a standard 3 + 3 design. In the first part of the study, different doses of enzalutamide will be tested. In the second part of the study, all patients will be started at the same dose of enzalutamide.

Also known as: MDV3100, XTANDI®, androgen receptor (AR) antagonist

Dose Escalation and Dose Expansion

Gemcitabine DRUG

The starting dose of gemcitabine will be 1000 mg/m\^2 administered intravenously on days 1, 8 and 15 of each cycle.

Also known as: nucleoside inhibitor, GEMZAR®

Dose Escalation and Dose Expansion

Nab-paclitaxel DRUG

The starting dose of nab-paclitaxel will be 125 mg/m\^2 administered intravenously on days 1, 8 and 15 of each cycle.

Also known as: albumin bound paclitaxel, microtubule inhibitor, Abraxane®

Dose Escalation and Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed pancreatic adenocarcinoma that is metastatic or unresectable. In the dose expansion phase, the tumor must express Androgen Receptor (AR) by immunohistochemistry. If ≥1% of the tumor cells express AR, it will be considered positive for this trial.
• Must have measurable disease per Response Criteria in Solid Tumors (RECIST) criteria version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status \<2 (Karnofsky \>60%)
• Life expectancy of greater than 3 months
• Must have normal organ and marrow function
• Prior treatment with gemcitabine alone or 5-Fluorouracil with radiation as an adjuvant therapy will be allowed; 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.
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of the study treatment.
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Prior treatment with any cytotoxic chemotherapy except as an adjuvant therapy. Participant 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.
• May not be receiving any other investigational agents within 4 weeks of starting the study treatment and during the study period.
• Untreated brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, nab-paclitaxel or enzalutamide.
• Have undergone major surgery within 4 weeks prior to starting the study treatment.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; history of myocardial infarction within 6 months of starting study treatment.
• Known history of human immunodeficiency virus (HIV) infection or active hepatitis B or hepatitis C
• Any history of seizure. History of loss of consciousness or transient ischemic attack within 12 months of starting the study drug.
• Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice an effective method of birth control
• Chronic treatment with immunosuppressant drugs
• Other malignancy requiring active treatment
• Any significant medical condition, laboratory abnormality, or psychiatric illness, that would prevent participating in the study, including the inability to swallow capsules
• Any active infection not controlled by antibiotics
• Concomitant medications that lower seizure threshold

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Astellas Pharma Inc: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms

Interventions

enzalutamide; Receptors, Androgen; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Tubulin Modulators

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Receptors, Steroid; Receptors, Cytoplasmic and Nuclear; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

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: May 12, 2014
• First Posted: May 14, 2014
• Study Start: May 22, 2014
• Primary Completion: December 15, 2016
• Study Completion: October 7, 2019
• Last Updated: August 17, 2021

Record last verified: 2021-08

Locations

US (1)