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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02667873
Recruitment Status : Terminated (Enrollment completed)
First Posted : January 29, 2016
Last Update Posted : February 11, 2022
Sponsor:
Information provided by (Responsible Party):
Stemline Therapeutics, Inc.

Study Description
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Brief Summary:
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

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: SL-801 Phase 1

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 28-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 approximately 70 adult patients at multiple study centers in the US.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of SL-801, a Novel Inhibitor of XPO1 Nuclear Export, in Patients With Advanced Solid Tumors
Actual Study Start Date : February 2016
Actual Primary Completion Date : January 2022
Actual Study Completion Date : January 2022
Arms and Interventions
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Arm Intervention/treatment
Experimental: SL-801
The starting dose regimen of SL-801 (i.e., the dose regimen in Cohort 1) is 5 mg/day on Days 1-4 and 8-11 every 21 days. In the 2nd portion of the dose escalation stage, patients receive SL-801 PO once daily on days 1-2, 8-9, 15-16 and 22-23 of a 28-day cycle. The starting dose will be 70 mg/day (the next planned dose level).The SL-801 dose regimen for a particular patient is dependent on the cohort in which the patient is enrolled
 Drug: SL-801
SL-801 is a small molecule inhibitor of the nuclear export protein Exportin-1 (XPO1).
Other Name: felezonexor


Outcome Measures
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Primary Outcome Measures :
  1. safety and tolerability: percentage of patients experiencing treatment-related and treatment-emergent adverse events [ Time Frame: up to 5 years ]
    The percentage of patients experiencing treatment-related and treatment-emergent adverse events

  2. maximum tolerated dose [ Time Frame: up to 5 years ]
    To identify the maximum tolerated dose (MTD) of SL-801 or determine the maximum tested dose at which multiple dose-limiting toxicities (DLTs) are not observed.


Secondary Outcome Measures :
  1. Duration of Response [ Time Frame: up to 5 years ]
    to evaluate the duration of response

  2. Progression Free Survival [ Time Frame: up to 5 years ]
    to evaluate progression free survive

  3. Overall Response Rate [ Time Frame: up to 5 years ]
    to evaluate overall response rate

  4. Overall Survival [ Time Frame: up to 5 years ]
    to evaluate overall survival

  5. Pharmacokinetic Profile [ Time Frame: up to 5 years ]
    Determine the maximum concentration of SL-801 in plasma


Eligibility Criteria
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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:

  • 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 28 days prior to study entry (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 28 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) or management of immune-mediated toxicities due to immunotherapy. Low-dose corticosteroid (defined as < 10mg/day of prednisone or equivalent) 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.
Contacts and Locations
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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): NCT02667873


Locations
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United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520
United States, Florida
Florida Cancer Specialist
Sarasota, Florida, United States, 34236
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Mary Crowely Cancer Research Centers- Medical City
Dallas, Texas, United States, 75230
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Washington
University of Washington, Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Stemline Therapeutics, Inc.
More Information
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Publications:
International Conference on Harmonisation. E8: General Considerations of for Clinical Trials, July 1997.
Lassen UN, Mau-Soerensen M, Kung AL, Wen PY, Lee EQ, Plotkin SR, et al. A phase 2 study on efficacy, safety and intratumoral pharmacokinetics of oral selinexor (KPT-330) in patients with recurrent glioblastoma (GBM). J Clin Oncol 33, 2015 (suppl; abstr 2044)
Tan DSP, Pang M-Y, Yong WP, Soo RA, Chee CE, Thian YL et al. Phase I study of the safety and tolerability of the Exportin 1 (XPO1) inhibitor Selinexor (SXR) in Asian patients (pts) with advanced solid cancers. J Clin Oncol 33, 2015 (suppl; abstr 2542).

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Responsible Party: Stemline Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02667873    
Other Study ID Numbers: STML-801-0115
First Posted: January 29, 2016    Key Record Dates
Last Update Posted: February 11, 2022
Last Verified: January 2022
Additional relevant MeSH terms:
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Neoplasms