Clinical Trials /

A Phase 1 Trial of a Novel XPO1 Inhibitor in Patients With Advanced Solid Tumors

NCT02667873

Description:

Study SL-801-0115 is a dose-escalation study evaluating multiple doses and schedules of orally administered SL-801 in patients with Advanced Solid Tumors

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Trial of a Novel XPO1 Inhibitor in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1 Trial of SL-801, a Novel Inhibitor of XPO1 Nuclear Export, in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: STML-801-0115
  • NCT ID: NCT02667873

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
SL-801SL-801

Purpose

Study SL-801-0115 is a dose-escalation study evaluating multiple doses and schedules of orally administered SL-801 in patients with Advanced Solid Tumors

Detailed Description

      Study SL-801-0115 is a first-in-human, dose-escalation study in patients with advanced
      (i.e., metastatic or locally advanced and unresectable) solid tumors that are resistant to
      or relapsed following available standard systemic therapy or for which there is no standard
      systemic therapy and additional radiation therapy or other loco-regional therapies are not
      considered feasible. Eligible patients will be enrolled and receive treatment with SL-801 in
      a 21-day cycle. SL-801 will be administered orally and the dose regimen will depend on the
      cohort in which the patient is enrolled.

      The study plans to enroll 40-50 adult patients at multiple study centers in the US.
    

Trial Arms

NameTypeDescriptionInterventions
SL-801ExperimentalThe study medication, SL-801 consists of tablets to be administered orally. The initial planned schedule involves administration daily on Days 1 through Day 4 and Days 8 through Day 11 of each cycle of therapy. A cycle of therapy is 21 days. The scheduled starting dose is 5 mg.
  • SL-801

Eligibility Criteria

        Inclusion Criteria:

          -  The patient must have histologic or cytologic evidence of a malignant solid tumor and
             must have disease that is resistant to or relapsed following available standard
             systemic therapy, or for which there is no standard systemic therapy or reasonable
             therapy likely to result in clinical benefit.

          -  The patient must have advanced disease, defined as cancer that is either metastatic,
             OR locally advanced and unresectable (and for which additional radiation therapy or
             other locoregional therapies are not considered feasible).

          -  The patient must have disease that is measurable by standard imaging techniques, per
             the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), or
             evaluable per RECIST 1.1. (For patients with prior radiation therapy, measurable
             lesions must be outside of any prior radiation field[s], unless disease progression
             has been documented at that disease site subsequent to radiation.)

          -  The patient is ≥18 years old.

          -  The patient has an ECOG PS of 0-2.

          -  The patient has adequate baseline organ function, as demonstrated by the following:

               -  Serum creatinine ≤1.5 × institutional upper limit of normal (ULN) or calculated
                  creatinine clearance >30 mL/min.

               -  Serum albumin ≥2.5 g/dL.

               -  Bilirubin ≤1.5 × institutional ULN.

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 ×
                  institutional ULN (patients with hepatic metastases must have AST/ALT ≤5 times
                  ULN).

               -  International normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 × ULN;
                  and either partial thromboplastin time or activated partial thromboplastin time
                  (PTT or aPTT) ≤1.5 × ULN.

          -  The patient has adequate baseline hematologic function, as demonstrated by the
             following:

               -  Absolute neutrophil count (ANC) ≥1.5×10⁹/L

               -  Hemoglobin ≥8 g/dL, with no red blood cell (RBC) transfusions within the prior
                  14 days.

               -  Platelet count ≥100×10⁹/L, with no platelet transfusions within the prior 14
                  days.

          -  If the patient is a woman of child bearing potential (WOCBP), she has had a negative
             serum or urine pregnancy test within 1 week prior to treatment.

          -  The patient (male and female) agrees to use acceptable contraceptive methods for the
             duration of time on the study, and continue to use acceptable contraceptive methods
             for 1 month after the last dose of SL-801.

          -  The patient has signed informed consent prior to initiation of any study-specific
             procedures or treatment.

          -  The patient is able to adhere to the study visit schedule and other protocol
             requirements, including follow-up for survival assessment.

        Exclusion Criteria:

          -  The patient has persistent clinically significant ≥Grade 2 toxicities from previous
             anticancer therapy (excluding Grade 2 chemotherapy-related neuropathy which is
             permitted, and excluding Grade 2-3 laboratory abnormalities if they are not
             associated with symptoms, are not considered clinically significant by the
             Investigator, and can be managed with available medical therapies).

          -  The patient has received treatment with chemotherapy, external-beam radiation, or
             other systemic anticancer therapy within 14 days prior to C1D1 (28 days for prior
             nitrosourea or mitomycin-C). (Patients with advanced prostate cancer who are
             receiving luteinizing hormone releasing hormone [LHRH] agonists are permitted onto
             the study and should continue use of these agents during study treatment).

          -  The patient has received treatment with an investigational systemic anticancer agent
             within 14 days prior to C1D1.

          -  The patient has previously received treatment with SL-801 or another investigational
             agent that inhibits the XPO1/CRM1 pathway.

          -  The patient has an additional active malignancy that may confound the assessment of
             the study endpoints. Patients with a past cancer history (active malignancy within 2
             years prior to study entry) with substantial potential for recurrence must be
             discussed with the Sponsor before study entry. Patients with the following
             concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in
             situ (including transitional cell carcinoma, cervical intraepithelial neoplasia),
             organ-confined prostate cancer with no evidence of progressive disease.

          -  The patient has clinically significant cardiovascular disease (e.g., uncontrolled or
             any New York Heart Association Class 3 or 4 congestive heart failure [Appendix 1],
             uncontrolled angina, history of myocardial infarction, unstable angina or stroke
             within 6 months prior to study entry, uncontrolled hypertension or clinically
             significant arrhythmias not controlled by medication).

          -  The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic
             obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's
             opinion, would put the patient at significant risk for pulmonary complications during
             the study.

          -  The patient has known active or suspected brain or leptomeningeal metastases.
             (Central nervous system [CNS] imaging is not required prior to study entry unless
             there is a clinical suspicion of CNS involvement). Patients with stable, treated
             brain metastases are eligible provided there is no evidence of CNS disease growth on
             imaging for at least 3 months following radiation therapy or other locoregional
             ablative therapy to the CNS.

          -  The patient is receiving immunosuppressive therapy for prophylaxis following a prior
             organ transplant (solid organ or allogeneic stem cell). Low-dose corticosteroid
             therapy is permitted.

          -  The patient has uncontrolled intercurrent illness including, but not limited to,
             uncontrolled infection, disseminated intravascular coagulation, or psychiatric
             illness/social situations that would limit compliance with study requirements.

          -  The patient is pregnant or breast feeding.

          -  The patient has known positive status for human immunodeficiency virus active or
             chronic Hepatitis B or Hepatitis C.

          -  The patient is oxygen-dependent.

          -  The patient has any medical condition which in the opinion of the Investigator places
             the patient at an unacceptably high risk for toxicities.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety
Time Frame:Up to 2 years
Safety Issue:
Description:The percentage of patients experiencing treatment-related and treatment-emergent adverse events

Secondary Outcome Measures

Measure:Determine the half-life of SL-801in plasma
Time Frame:Up to 2 Years
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Overall Response Rate
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:Up to 2 Years
Safety Issue:
Description:
Measure:Determine the maximum concentration of SL-801 in plasma
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Stemline Therapeutics, Inc.

Last Updated

January 31, 2017