Safety and Tolerability Study in Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01803282
First received: February 27, 2013
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

This is an open-label, multicenter, sequential dose-escalation, and expansion study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of GS-5745 alone and in combination with chemotherapy.

The study consists of 2 parts (Parts A and B). Participants can only qualify for and participate in 1 part.

Part A is a sequential dose escalation to determine the maximum tolerated dose of GS-5745 in participants with advanced solid tumors that are refractory to or intolerant to standard therapy or for which no standard therapy exists. In Part A, participants will receive GS-5745 only. Part A will consist of between 12 to 54 participants.

Part B is a dose expansion to obtain additional safety and tolerability data with GS-5745 in participants with advanced pancreatic adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, or esophagogastric adenocarcinoma. In Part B, participants will receive GS-5745 in combination with standard-of-care chemotherapy. Part B will consist of between 70 to 145 participants.


Condition Intervention Phase
Tumors
Pancreatic Cancer
Non-small Cell Lung Cancer
Esophagogastric Cancer
Drug: GS-5745
Drug: Chemotherapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5745 as Monotherapy and in Combination With Chemotherapy in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Safety as evaluated by incidence of AEs, assessment of clinical laboratory test findings, physical examination, 12-lead ECG, and vital signs measurements [ Time Frame: Baseline to completion of follow up evaluation. If follow up evaluation is not completed, baseline to date of first documented progression or date of death from any cause, whichever came first ] [ Designated as safety issue: No ]
    AEs that begin on or after the first study drug administration and within 30 days after last study drug administration will be summarized by dose level (Part A) and tumor type (Part B).


Estimated Enrollment: 199
Study Start Date: March 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GS-5745
Participants will receive GS-5745 by intravenous (IV) infusion over approximately 30 minutes every 2 weeks.
Drug: GS-5745
GS-5745 is a humanized monoclonal antibody against matrix metalloproteinase 9.
Experimental: GS-5745 with chemotherapy
Participants will receive GS-5745 by IV infusion every 2-3 weeks in combination with chemotherapy.
Drug: GS-5745
GS-5745 is a humanized monoclonal antibody against matrix metalloproteinase 9.
Drug: Chemotherapy

In Part B, GS-5745 will be given in combination with one of the following chemotherapy regimens:

  • Pancreatic adenocarcinoma: gemcitabine and nab-paclitaxel
  • Esophagogastric adenocarcinoma: mFOLFOX6
  • Lung adenocarcinoma: carboplatin and pemetrexed
  • Lung squamous cell carcinoma: carboplatin and paclitaxel

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female > 18 years of age
  2. Part A: histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available
  3. Part B Pancreatic Adenocarcinoma:

    a. Presence of histologically confirmed inoperable locally advanced or metastatic pancreatic adenocarcinoma

  4. Part B NSCLC:

    1. Stage IIIB with malignant pleural effusion/pleural seeding or stage IV histologically confirmed NSCLC
    2. Absence of known epidermal growth factor receptor (EGFR) mutation
    3. Absence of known translocation or inversion events involving the ALK gene locus (resulting in EML4-ALK fusion)
  5. Part B Esophagogastric Adenocarcinoma:

    1. Histologically confirmed inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the gastrooesophageal junction) or relapsed gastric adenocarcinoma
    2. Human epidermal growth factor receptor 2 (HER2)-negative tumor (primary tumor or metastatic lesion)
  6. All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before the start of study drug dosing (with the exception of alopecia [Grade 1 or 2 permitted] and neurotoxicity [Grade 1 or 2 permitted])
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
  8. Life expectancy of > 3 months in the opinion of the Investigator
  9. Adequate organ function defined as follows:

    1. Hematologic: Platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 9.0 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
    2. Hepatic: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN
    3. Renal: Serum Creatinine ≤ 1.5 x ULN
  10. Coagulation: international normalized ratio (INR) ≤ 1.6 (unless receiving anticoagulation therapy). Subjects on full-dose oral anticoagulation must be on a stable dose (minimum duration 14 days). If receiving warfarin, the subject must have an INR ≤ 3.0 and no active bleeding (ie, no bleeding within 14 days prior to first dose of study drug). Subjects on low molecular weight heparin will be allowed.
  11. For female subjects of childbearing potential, willingness to use a protocol-recommended method of contraception from the screening visit throughout the study treatment period and for 90 days following the last dose of study drugs. Note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone [FSH] levels within the institutional postmenopausal range and a negative serum or urine Beta-HCG), or is menopausal (age > 55 years with amenorrhea for > 6 months).
  12. For male subjects of childbearing potential having intercourse with females of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of study drug, throughout the study treatment period, and for 90 days following the last dose of study drugs, and to refrain from sperm donation from the start of study drug, throughout the study treatment period, and for 90 days following the last dose of study drugs. Note: A male subject is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy, or has ongoing testicular suppression with a depot luteinizing hormone releasing hormone (LH RH) agonist (eg, goserelin acetate [Zoladex®]), leuprolide acetate [Lupron®]), or triptorelin pamoate [Trelstar®]).
  13. Willingness to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions
  14. Evidence of a signed informed consent form

Exclusion Criteria:

  1. History or evidence of clinically significant disorder, condition, or disease that, in the opinion of the Investigator and Medical Monitor would pose a risk to subject safety or interfere with the study evaluations, procedures, or completion
  2. Pregnant or lactating
  3. Subject with known central nervous system (CNS) metastases, unless metastases are treated and stable and the subject does not require systemic steroids
  4. For Part B, small cell lung cancer
  5. For Part B, diagnosis of pancreatic islet cell neoplasm
  6. For Part B, subjects who have received prior cytotoxic chemotherapy to treat their metastatic disease
  7. Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of study Day 1
  8. History of major surgery within 28 days prior to enrollment
  9. Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires IV antibiotics
  10. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within 28 days or 5 half-lives, whichever is shorter, of study drug dosing (6 weeks for nitrosoureas, mitomycin C, or molecular agents with t½ > 10 days); concurrent use of hormone therapy for breast or prostate cancer is permitted
  11. Clinically significant bleeding within 28 days of Day 1
  12. Subjects known to be positive for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01803282

Locations
United States, Alabama
Alabama Oncology Recruiting
Birmingham, Alabama, United States, 35223
Contact: Bobbie Parks    205-599-4929    bobbie.parks@alabamaoncology.com   
Principal Investigator: Kevin Windsor, MD         
United States, Arizona
Pinnacle Oncology Hematology Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Kristina Will    480-860-5000    kwill@azpoh.com   
Principal Investigator: Michael Gordon, MD         
United States, California
Comprehensive Blood and Cancer Center Recruiting
Bakersfield, California, United States, 93309
Contact: Jami Coughran    661-862-8548    jcoughran@cbccusa.com   
Principal Investigator: Ravindranath Patel, MD         
UCLA Medical Center Recruiting
Santa Monica, California, United States, 90404
Contact: Lisa Yonemoto    310-582-4069    lyonemoto@mednet.ucla.edu   
Principal Investigator: Zev Wainberg, MD         
Stanford University Withdrawn
Stanford, California, United States, 94305
United States, Florida
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Jill Martin    941-377-9993 ext 319    jimartin@flcancer.com   
Principal Investigator: Manish Patel, MD         
United States, Indiana
Indiana University Health Goshen Center for Cancer Care Recruiting
Goshen, Indiana, United States, 46526
Contact: Tracy Thorne    574-364-2439    tthorne@iuhealth.org   
Principal Investigator: Alexander Starodub, MD         
United States, New York
Cornell University Recruiting
New York, New York, United States, 10065
Contact: Hayley Sacks    646-962-9343    has2021@med.cornell.edu.edu   
Principal Investigator: Manish Shah, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Gina Courtney    615-329-6823    gina.courtney@scresearch.net   
Principal Investigator: Johanna Bendell, MD         
Vanderbilt Recruiting
Nashville, Tennessee, United States, 37232
Contact: Shaunita Michael    615-936-5795    shaunita.michael@vanderbilt.edu   
Principal Investigator: Jordan Berlin, MD         
United States, Texas
UT Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Adrian Avila    214-648-5107    adrian.avila@Utsouthwestern.edu   
Principal Investigator: Saad Khan, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Bryant Gordon    801-587-4771    bryant.gordon@hci.utah.edu   
Principal Investigator: Sunil Sharma, MD         
United States, Washington
Northwest Medical Specialties Recruiting
Tacoma, Washington, United States, 98405
Contact: Sue Quinsey    253-428-8738    squinsey@nwmsonline.com   
Principal Investigator: Jorge Chaves, MD         
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Dung Thai, MD, PhD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01803282     History of Changes
Other Study ID Numbers: GS-US-296-0101
Study First Received: February 27, 2013
Last Updated: September 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Solid Tumor
NSCLC
Pancreatic
Esophagogastric

Additional relevant MeSH terms:
Pancreatic Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 16, 2014