Trial record 3 of 10 for:    snx5422

Safety and Pharmacology of SNX-5422 Plus Everolimus in Subjects With Neuroendocrine Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Esanex Inc.
Sponsor:
Information provided by (Responsible Party):
Esanex Inc.
ClinicalTrials.gov Identifier:
NCT02063958
First received: February 13, 2014
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

Study is designed to determine the maximum tolerated dose (MTD) of SNX-5422 when given in combination with everolimus.


Condition Intervention Phase
Cancer
Drug: SNX-5422
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label, Dose-escalation Study of SNX 5422 and Everolimus in Subjects With Neuroendocrine Tumors.

Resource links provided by NLM:


Further study details as provided by Esanex Inc.:

Primary Outcome Measures:
  • Number of patients with dose limiting toxicities [ Time Frame: First 28 day cycle ] [ Designated as safety issue: Yes ]
    Number of patients with dose limiting toxicities defined as adverse events or laboratory abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 ≥ Grade 3 that are not clearly related to disease progression or delay by more than 4 weeks in receiving the next scheduled cycle due to persisting toxicities and attributable to the combination of SNX-5422 and everolimus despite optimal medical supportive management.


Secondary Outcome Measures:
  • Number of patients with adverse events as a measure of tolerability [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]
    Frequency and severity of adverse events

  • Changes in ECG, vital signs, laboratory or physical examination [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]
    Changes in ECG, vital signs, laboratory or physical examination from baseline

  • Tumor response [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
    Measurements from tumor imaging within 1 month prior to the screening visit will be used as the baseline assessment. This assessment will be performed using Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Follow-up imaging of known sites of the disease, preferably by CT scan, will be performed at intervals appropriate to the subject's disease and clinical findings.


Estimated Enrollment: 15
Study Start Date: February 2014
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SNX-5422
Open-label administration of SNX-5422 capsules dosed in the morning once every other day (qod) for 21 days (11 doses), followed by a 7 day drug free period. Dose escalation will be based on safety defined as 1 or less dose limiting toxicities during the first 28 day cycle at any dose level. Dose escalation will not exceed a dose of 100 mg/m2 SNX-5422 qod even if the MTD has not been identified. Subjects will receive daily oral everolimus in the PM about the same time every day for 28 days.
Drug: SNX-5422
Capsule dosed every other day for 21 days out of a 28 day cycle. Dose escalation based on safety not to exceed a dose of 100 mg/m2. Maintenance therapy of SNX-5422 at the MTD will be allowed for all patients not experiencing significant toxicity.

Detailed Description:

Heat shock protein 90 (Hsp90) plays a central role in the maturation and maintenance of numerous proteins, for example HER2 and mutated EGFR, that are critical for tumor cell viability and growth; SNX-5422 is a pro-drug of SNX-2112, a potent, highly selective, small-molecule inhibitor of the molecular chaperone heat shock protein 90 (Hsp90). Hsp90 has been found to be expressed in 95% of subjects with pancreatic neuroendocrine tumors.

This study will determine the MTD of SNX-5422 when given in combination with everolimus in patients with neuroendocrine tumors.The clinical starting dose of 50 mg/m2 qod for SNX-5422 in combination with daily everolimus is 50% of the SNX-5422 qod mono-therapy MTD. The choice to continue once every other day SNX-5422 dosing is based on the safety and efficacy profiles from prior studies, so that drug holidays are interspersed into weekly dosing. The planned subsequent dose levels are 75% and 100% of the SNX-5422 qod mono-therapy MTD.

  Eligibility

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

Inclusion Criteria:

  • Males or non-pregnant, non-breastfeeding females 18 years-of-age or older.
  • Archived neuroendocrine tumor sample or biopsy sample (will also be used for genetic testing).
  • Pathologic evidence of locally advanced or metastatic neuroendocrine tumor of gastro-entero-pancreatic or pulmonary origin.
  • Measurable (RECIST) indicator lesion not previously irradiated.
  • Life expectancy of at least 3 months.
  • No more than 4 prior lines of systemic anti-cancer therapy.
  • Karnofsky performance score ≥70.
  • Adequate baseline laboratory assessments, including

    • Absolute neutrophil count (ANC) ≥1.5 x 109/L.
    • WBC >3000/microliter
    • Platelet count of ≥100 x 109/L.
    • Total bilirubin level ≤1.5 times institutional upper limit of normal (ULN), alanine aminotransferase or aspartate aminotransferase ≤2 x ULN
    • Hemoglobin ≥9 mg/dL.
    • Creatinine <1.5 X upper limit of normal or estimated plasma creatinine clearance of ≥40 mL/min
  • Signed informed consent form
  • Recovered from toxicities of previous anticancer therapy
  • Subjects with reproductive capability must agree to practice adequate contraception methods.

Exclusion Criteria:

  • Subjects in whom everolimus is contraindicated.
  • Subjects with clinically significant interstitial lung disease, or obstructive disease without sufficient reserve
  • Carcinoid with hormone related symptoms
  • Neuroendocrine cancer of the thyroid or thymus.
  • Rare pancreatic neuroendocrine cancers such as, insulinomas, glucagonomas, gastrinomas.
  • Prior treatment with any Hsp90 inhibitor.
  • Prior failed treatment with mTOR inhibitors
  • CNS metastases that are symptomatic and /or requiring escalating doses of steroids.
  • Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
  • Conventional chemotherapy or radiation within 4 weeks.
  • Palliative radiation within 2 weeks.
  • The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422
  • Screening ECG QTc interval ≥470 msec for females, ≥450 msec for males.
  • At increased risk for developing prolonged QT interval, including hypokalemia or hypomagnesemia, unless corrected to within normal limits prior to first dose of SNX-5422; congenital long QT syndrome or a history of torsade de pointes; currently receiving anti-arrhythmics or other medications that may be associated with QT prolongation.
  • Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.
  • Gastrointestinal diseases or conditions that could affect drug absorption, including gastric bypass.
  • Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
  • History of documented adrenal dysfunction not due to malignancy.
  • Known seropositive for human immunodeficiency virus (HIV) or hepatitis C virus (HCV).
  • History of chronic liver disease.
  • Active hepatitis A or B.
  • Current alcohol dependence or drug abuse.
  • Use of an investigational treatment from 30 days prior to the first dose of SNX-5422 and during the study.
  • Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination.
  • Other serious concurrent illness or medical condition.
  • Psychological, social, familial, or geographical reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.
  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: NCT02063958

Contacts
Contact: Eric Orlemans, PhD eorlemans@esanexpharma.com

Locations
United States, District of Columbia
Georgetown University Medical Center Not yet recruiting
Washington, District of Columbia, United States, 20007
Contact: Guiseppe Giaccone, MD    202-687-5791    gg496@georgetown.edu   
Contact: Sharon G Levy, RN    202-687-8921    sgl5@georgetown.edu   
Principal Investigator: Guiseppe Giaccone, MD         
United States, New Jersey
hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Martin Gutierrez, MD    551-996-5900    mgutierrez@hackensackUMC.org   
Principal Investigator: Martin Gutierrez, MD         
Sponsors and Collaborators
Esanex Inc.
  More Information

No publications provided

Responsible Party: Esanex Inc.
ClinicalTrials.gov Identifier: NCT02063958     History of Changes
Other Study ID Numbers: SNX5422-CLN-009
Study First Received: February 13, 2014
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Esanex Inc.:
Neuroendocrine tumor
Hsp90

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014