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RX-3117 in Combination With Abraxane® in Subjects With Metastatic Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT03189914
Recruitment Status : Recruiting
First Posted : June 16, 2017
Last Update Posted : December 5, 2018
Sponsor:
Information provided by (Responsible Party):
Rexahn Pharmaceuticals, Inc.

Brief Summary:
This will be a Phase 1b/2a multicenter 2-stage study. Phase 1 will be conducted as a dose-finding, open-label study of oral RX-3117 administered in combination with Abraxane® to subjects with metastatic pancreatic cancer. After completion of the Phase 1 portion, a Phase 2a study will be conducted using a 2 stage, open-label design, of RX 3117 and Abraxane® in combination to treat subjects with metastatic pancreatic cancer as first line therapy.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Cancer Drug: RX-3117 Phase 1 Phase 2

Detailed Description:

This will be a Phase 1b/2a multicenter 2-stage study. Phase 1 will be conducted as a dose-finding, open-label study of oral RX-3117 administered in combination with Abraxane® to subjects with metastatic pancreatic cancer. The recommended phase 2 dose (RP2D) and schedule of RX-3117, in combination with Abraxane®, will be determined based on the safety profile, dose modification, and pharmacokinetics (PK). Phase 1 will be conducted using a combination of the single agent maximum tolerated dose (MTD) for RX-3117 and the Abraxane dose as per the package insert for patients with pancreatic cancer in combination with gemcitabine.

After completion of the Phase 1 portion, a Phase 2a study will be conducted using a 2 stage, open-label design, of RX 3117 and Abraxane® in combination to treat subjects with metastatic pancreatic cancer as first line therapy. Approximately 10 subjects will participate in the Stage 1 at the dose identified in Phase 1 (RP2D). Subjects will be treated for up to 8 cycles of combined therapy. An interim analysis will be conducted after 10 evaluable subjects have been treated at the RP2D, have completed a minimum of 4 cycles of therapy, or have discontinued therapy due to progressive disease before completing 4 cycles. If an adequate number of Responders are observed out of the initial 10 evaluable subjects, then 40 additional subjects will be enrolled to participate in Stage 2. Subjects will be treated for up to 8 cycles of combined therapy.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-Label, Safety, Pharmacokinetic, Pharmacodynamic and Efficacy Study of RX-3117 in Combination With Abraxane® in Subjects With Metastatic Pancreatic Cancer
Actual Study Start Date : October 2, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

Arm Intervention/treatment
Experimental: RX-3117 + Abraxane

RX-3117: oral, 500 - 700 mg/ day for 5 days on/ 2 days off for 3 weeks. 1 washout week/ cycle.

Abraxane: 75 - 125 mg/m^2, infused once per week for 3 weeks. 1 washout week/ cycle.

Drug: RX-3117
RX-3117 will be administered orally in combination with Abraxane.
Other Name: Abraxane




Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (Phase 1 and 2) [ Time Frame: 9 months ]
    Type, frequency, severity, timing of onset, duration and relationship to study therapies of any adverse events (AEs)

  2. Number of participants with Clinical laboratory abnormalities (Phase 1 and 2) [ Time Frame: 9 months ]
    Type, frequency, severity, timing of onset, duration and relationship to study therapies of any clinical laboratory abnormalities

  3. Number of participants with Vital sign abnormalities (Phase 1 and 2) [ Time Frame: 9 months ]
    Type, frequency, severity, timing of onset, duration and relationship to study therapies of any vital signs including heart rate, respiration rate, and blood pressure

  4. Number of participants with Electrocardiogram (ECG) abnormalities (Phase 1 and 2) [ Time Frame: 1 month ]
    Type, frequency, severity, timing of onset, duration and relationship to study therapies of any electrocardiograms (ECGs)

  5. Incidence of dose-limiting toxicities (DLTs) (Phase 1) [ Time Frame: 4 weeks ]
  6. Number of participants with Progression Free Survival (PFS) and/or objective clinical response (Phase 2) [ Time Frame: 9 months ]

Secondary Outcome Measures :
  1. Area under the plasma concentration versus time curve (AUC) of RX-3117 and Abraxane® (Phase 1 and Phase 2) [ Time Frame: Cycle 1 Days 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration) and 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration) ]
  2. Time to maximum observed concentration [Tmax] of RX-3117 and Abraxane® (Phase 1 and Phase 2) [ Time Frame: Cycle 1 Days 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration) and 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration) ]
  3. Maximum observed concentration [Cmax] of RX-3117 and Abraxane® (Phase 1 and Phase 2) [ Time Frame: Cycle 1 Days 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration) and 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration) ]
  4. Overall response rate [ORR] (Phase 1 and Phase 2) [ Time Frame: Baseline, and at 8, 6, 24, and 32 weeks ]
  5. Time to response [TTR] (Phase 1) [ Time Frame: Baseline, and at 8, 6, 24, and 32 weeks ]
  6. Duration of response [DOR] (Phase 1 and Phase 2) [ Time Frame: Baseline, and at 8, 6, 24, and 32 weeks ]
  7. Number of participants with Progression-free survival [PFS] (Phase 1) [ Time Frame: Baseline, and at 8, 6, 24, and 32 weeks ]
  8. Time to progression (Phase 2) [ Time Frame: Baseline, and at 8, 6, 24, and 32 weeks ]

Other Outcome Measures:
  1. Exploratory measurement of protein biomarkers related to RX-3117 or pancreatic cancer (Phase 1 and 2) [ Time Frame: Baseline, and at 8, 6, 24, and 32 weeks ]
  2. Tumor burden response (Phase 2) [ Time Frame: Baseline, and at 8, 6, 24, and 32 weeks ]
    Changes in tumor burden response via tumor marker measurement

  3. Quality of Life (QOL) (Phase 1 and 2) [ Time Frame: 9 months ]
    Weekly patient reported quality of life measures using validated QOL questionnaires



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Disease Related

  1. Subject has confirmed histologic or cytologic evidence of metastatic pancreatic cancer and has no prior treatment for metastatic pancreatic cancer.
  2. Subject has measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1.
  3. Subject has a life expectancy of at least 3 months.
  4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

    Demographic

  5. Males or females ≥ 18 years of age
  6. Subject must be able to swallow capsules
  7. Subject must have adequate venous access for intravenous (IV) infusion

    Laboratory

  8. Subject has hemoglobin ≥ 9.0 g/dL at Screening
  9. Subject has absolute neutrophil count (ANC) ≥ 1.5 x 109/L at Screening
  10. Subject has platelet count ≥ 100 x 109/L at Screening
  11. Subject has serum creatinine ≤ 1.5 times the upper limit of normal (ULN) at Screening. Subjects with serum creatinine levels > 1.5 times the ULN must have a 24-hour urine creatinine clearance ≥ 60 mL/min
  12. Subject has serum bilirubin ≤ 1.5 times the ULN (except in subjects with Gilbert's Syndrome who must have serum bilirubin < 3.0 x ULN)
  13. Subject has aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) ≤ 2.5 times the ULN (OR, AST and ALT ≤ 5 times the ULN in the presence of known liver metastases)
  14. Subject has alkaline phosphatase ≤ 2.5 times the ULN (OR ≤ 5 times the ULN in the presence of known liver or bone metastases)
  15. Subject has normal coagulation parameters (prothrombin time [PT] and/or international normalized ratio [INR], and partial thromboplastin time [PTT] within normal limits [<1.2 x ULN])
  16. Subject has potassium concentration within normal range, or correctable with supplements.
  17. Oxygen saturation by pulse oximetry ≥ 92% at rest.
  18. For women of childbearing potential: Negative serum pregnancy test during screening and negative serum or urine pregnancy test at start of study therapy (Cycle1 Day 1).

    Reproductive

  19. For female subjects of childbearing potential, willingness to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from the screening visit throughout the study treatment period and for 30 days following the last dose of study drug.
  20. Female subjects of non-childbearing potential defined as having amenorrhea for at least 24 consecutive months, a documented hysterectomy, or a documented bilateral oophorectomy)
  21. For fertile male subjects having intercourse with females of childbearing potential, willingness to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from the start of study therapy throughout the study treatment period and for 30 days following the last dose of study drug and to refrain from sperm donation from the start of study treatment throughout the study treatment period and for 30 days following the last dose of study drug.

    Ethical

  22. In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject's cancer.
  23. Before any study-specific procedure, the appropriate written informed consent must be obtained

Exclusion Criteria:

Disease Related

  1. Subject has primary brain tumors or clinical evidence of active brain metastasis
  2. Subject has undergone major surgery within 4 weeks of the start of study treatment. Laparoscopy and central venous catheter placement are not considered major surgery

    Medications

  3. Subject has a history of systemic corticosteroid use within 7 days before Day 1 of Cycle 1

    General

  4. Subject has an active infection requiring parenteral or oral antibiotics within 2 weeks before planned start of study therapy
  5. Subject has uncontrolled diabetes as assessed by the investigator
  6. Subject has a second malignancy other than curatively resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ carcinoma of the cervix, or other cancers treated with curative intent and no known active disease within 3 years before planned start of study therapy
  7. Subject has an active infection of hepatitis B, hepatitis C or human immunodeficiency virus
  8. Female subjects who are pregnant, planning a pregnancy or breast feeding during the study
  9. Subject has a high cardiovascular risk, including, but not limited to, subjects with congestive heart failure (New York Heart Association [NYHA] Class III or IV), cardiac arrhythmia, unstable angina, coronary stenting or acute coronary syndromes within 6 months before planned start of study therapy or r myocardial infarction within one year before planned start of study therapy
  10. Subject has a history of peripheral artery disease (e.g., claudication, Leo Buerger's disease).
  11. Subject has a history of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
  12. Subject has known acute or chronic pancreatitis.
  13. Subject has persistent diarrhea, malabsorption, or known sub-acute bowel obstruction ≥ NCI CTCAE Grade 2, despite medical management.
  14. Subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery and bariatric surgery)
  15. All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before the start of study therapy (with the exception of alopecia [Grade 1 or 2 permitted], or neurotoxicity [Grade 1 or 2 permitted], or anemia [Grade 2 permitted])
  16. Subject has any other medical, psychiatric, or social condition, which in the opinion of the investigator, would preclude participation in the study, pose an undue medical hazard, interfere with the conduct of the study, or interfere with interpretation of the study results
  17. Subject has a history of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies. Any lung disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  18. Subject is currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug.
  19. Subject has a history of hypersensitivity to RX-3117, gemcitabine, azacytidine cytosine arabinoside, paclitaxel, nab-paclitaxel, or their excipients.
  20. Subject is unwilling or unable to comply with study requirements or planned unavailability for follow-up assessments.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03189914


Contacts
Contact: Callie Heaton 240-268-5300 ext 312 heatonc@rexahn.com
Contact: Christine Peterson, PhD 240-268-5300 ext 320 petersonc@rexahn.com

Locations
United States, Arizona
Rexahn Site Recruiting
Tucson, Arizona, United States, 85724
United States, Florida
Rexahn Site Recruiting
Weeki Wachee, Florida, United States, 34607
United States, Illinois
Rexahn Site Recruiting
Joliet, Illinois, United States, 60435
Rexahn Site Recruiting
Skokie, Illinois, United States, 60077
United States, Kentucky
Rexahn Site Recruiting
Lexington, Kentucky, United States, 40503
United States, Massachusetts
Rexahn Site Recruiting
Boston, Massachusetts, United States, 02115
United States, New York
Rexahn Site Recruiting
New York, New York, United States, 10065
United States, South Carolina
Rexahn Site Recruiting
Spartanburg, South Carolina, United States, 29303
United States, Texas
Rexahn Site Recruiting
Arlington, Texas, United States, 76012
United States, Washington
Rexahn Site Recruiting
Spokane, Washington, United States, 99202
United States, Wisconsin
Rexahn Site Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Rexahn Pharmaceuticals, Inc.
Investigators
Study Director: Ely Benaim, MD Rexahn Pharmaceuticals, Inc.

Responsible Party: Rexahn Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03189914     History of Changes
Other Study ID Numbers: RX3117-003
First Posted: June 16, 2017    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rexahn Pharmaceuticals, Inc.:
pancreatic cancer
Abraxane
first line

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Albumin-Bound Paclitaxel
Paclitaxel
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action