Clinical Trials /

Phase 1/2 Trial of Selinexor (KPT-330) With Docetaxel for Non-small Cell Lung Cancer (NSCLC)

NCT03095612

Description:

This study is being done to evaluate the safety of the investigational study drug, selinexor when given with docetaxel to patients who have been previously treated for advanced KRAS mutant lung cancer.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/2 Trial of Selinexor (KPT-330) With Docetaxel for Non-small Cell Lung Cancer (NSCLC)
  • Official Title: An Investigator-Sponsored, Phase 1/2 Trial of the Oral XPO1 Inhibitor Selinexor (KPT-330) in Combination With Docetaxel for Previously Treated, Advanced KRAS Mutant Non-small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: STU 032017-003
  • NCT ID: NCT03095612

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
SelinexorKPT-330Selinexor in Combination with Docetaxel

Purpose

This study is being done to evaluate the safety of the investigational study drug, selinexor when given with docetaxel to patients who have been previously treated for advanced KRAS mutant lung cancer.

Detailed Description

      This is a phase 1/2 clinical trial of the oral XPO1 inhibitor selinexor (KPT-330) in
      combination with docetaxel for previously treated, advanced KRAS mutant non-small cell lung
      cancer (NSCLC). It is a single-arm, non-blinded study, which will compare safety and outcomes
      with historical controls (docetaxel monotherapy). The multi-center study will be conducted
      within the Academic Thoracic Oncology Medical Investigator Consortium (ATOMIC).
    

Trial Arms

NameTypeDescriptionInterventions
Selinexor in Combination with DocetaxelExperimentalSelinexor will be administered once weekly starting one week before chemotherapy initiation in combination with docetaxel. Docetaxel will be given once every 3 weeks. Treatment will be administered in 21-day cycles. Selinexor dose escalation: 60, 80, 100, 40 mg once weekly. Docetaxel 75 mg/m2 IV, 60 every 3 weeks.
  • Selinexor

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must meet all of the following inclusion criteria to be eligible to enroll in
             this study:

               1. Written informed consent in accordance with federal, local, and institutional
                  guidelines. The patient must provide informed consent prior to the first
                  screening procedure.

               2. Age ≥ 18 years

               3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

               4. Histologically or cytologically confirmed advanced (stage 4, according to the
                  American Joint Committee on Cancer [AJCC] version 7.0 Staging manual) NSCLC

               5. Molecular identification of a KRAS mutation (codons 12, 13, or 61)

               6. Tissue available for analysis at time of enrollment for biomarker analysis (may
                  be obtained via biopsy prior to initiation of treatment, or submission of
                  available archival tissue): 10-15 slides, or 5 slides with 3 sections per slide

               7. At least one and up to two previous lines of systemic cytotoxic therapy for
                  advanced NSCLC, of which one must have been a platinum-based doublet therapy. Up
                  to four total previous lines of systemic therapy (including immunotherapy and
                  molecularly targeted therapy)

               8. Radiographic or clinical disease recurrence or progression during or after the
                  last line of systemic therapy

               9. Adequate hematologic function (absolute neutrophil count [ANC] ≥ 1500 cells/μL;
                  hemoglobin ≥ 9 g/dL; platelets ≥ 100,000/μL. Use of PRBC transfusion to achieve
                  Hgb ≥9.0 mg/dL is allowed.

              10. Adequate renal function (calculated creatinine clearance ≥ 30 mL/min using the
                  Cockcroft-Gault equation)

              11. Adequate hepatic function (total bilirubin ≤ upper limit of normal [ULN], alanine
                  aminotransferase [ALT] ≤ 2 × ULN and aspartate aminotransferase [AST] ≤ 2 × ULN).
                  ALT and/or AST may be ≤ 5 × ULN if due to liver metastases. If ALT or AST is > 2
                  and ≤ 5 × ULN in patients with liver metastases, alkaline phosphatase must be ≤
                  2.5 × ULN (unless elevated alkaline phosphatase clearly due to skeletal—rather
                  than hepatic—process; eg, normal GGT, presence of multiple bone metastases,
                  absence of bulky and/or central liver metastases). Patients with Gilbert's
                  syndrome are allowed if total bilirubin ≤ 2 × ULN and direct bilirubin is ≤ ULN.

              12. Prothrombin time (PT) and/or international normalized ratio (INR) ≤ 1.5 × ULN and
                  activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN if patient is not on
                  anticoagulant therapy (a therapeutic PT and/or INR and aPTT is acceptable if the
                  patient is on anticoagulants)

              13. Female patients of childbearing potential must agree to use 2 methods of
                  contraception (including 1 highly effective and 1 effective method of
                  contraception) and have a negative serum pregnancy test at Screening. Male
                  patients must use an effective barrier method of contraception if sexually active
                  with a female of childbearing potential. For both male and female patients,
                  effective methods of contraception must be used throughout the study and for 3
                  months following the last dose of study treatment. Female patients of
                  child-bearing potential must have a negative serum pregnancy test at screening
                  and agree to use 2 reliable methods of contraception throughout the study and for
                  3 months after their last dose of medication. Female patients are considered NOT
                  of childbearing potential if they have a history of surgical sterility (including
                  hysterectomy and/or bilateral oophorectomy, but not tubal ligation alone) or
                  evidence of post-menopausal status defined as any of the following:

                    -  Natural menopause with last menses >1 year ago and confirmed by FSH blood
                       level

                    -  Radiation-induced oophorectomy with last menses >1 year ago

                    -  Chemotherapy-induced menopause with last menses >1 year ago. Male patients
                       and their partners must use 2 reliable methods of contraception, at least
                       one of them a barrier method (if sexually active with a female of
                       child-bearing potential).

              14. Measurable disease according to RECIST v1.1

              15. Previously treated (surgery and/or radiation therapy) or untreated brain
                  metastases are eligible, provided that patients are asymptomatic and not
                  requiring escalating doses of corticosteroids

              16. Previous treatment-associated clinically significant toxicities resolved to CTCAE
                  grade ≤1 (except alopecia) or to their baseline

              17. At least 3 weeks or 5 half-lives, whichever is shorter, since receiving systemic
                  anticancer therapy, including investigational agents, prior to starting study
                  therapy. At least 2 weeks since receiving radiation therapy prior to starting
                  study therapy

        Exclusion Criteria:

          -  Patients meeting any of the following exclusion criteria are not eligible to enroll in
             this study:

               1. Patients who are pregnant or lactating

               2. Major surgery (excluding skin biopsies and procedures for insertion of central
                  venous access devices) within 2 weeks of first dose of study drug

               3. Any life-threatening illness, medical condition or organ system dysfunction
                  which, in the investigator's opinion, could compromise the patient's safety

               4. Presence of symptomatic brain metastases or brain metastases requiring the
                  escalating doses of corticosteroids to control neurological symptoms

               5. Other concurrent cancer (with the exception of non-melanoma skin cancer and
                  low-risk localized prostate cancer on active surveillance)

               6. Unstable cardiovascular function:

                    -  Symptomatic ischemia, or

                    -  Uncontrolled clinically significant conduction abnormalities (i.e.,
                       ventricular tachycardia on anti-arrhythmics is excluded; 1st degree AV block
                       or asymptomatic LAFB/RBBB are not excluded; asymptomatic rate controlled
                       atrial fibrillation is not excluded), or

                    -  Congestive heart failure (CHF) of NYHA Class ≥3, or

                    -  Myocardial infarction (MI) within 3 months

               7. Uncontrolled (i.e., clinically unstable) infection requiring parenteral
                  antibiotics, antivirals, or antifungals within one week prior to first dose;
                  however, prophylactic use of these agents is acceptable even if parenteral

               8. Pre-existing grade 3 or 4 neuropathy

               9. Active Hepatitis A, B or C infection

              10. Known human immunodeficiency virus (HIV) infection (HIV testing is not required
                  as part of this study)

              11. Patients unable to swallow tablets, patients with malabsorption syndrome, or any
                  other GI disease or GI dysfunction that could interfere with absorption of study
                  treatment

              12. Prior exposure to docetaxel, selinexor, or another selective inhibitor of nuclear
                  transport (SINE) compound

              13. Patients unwilling to comply with study protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:Each 21 day cycle for 2 years
Safety Issue:
Description:A standard 3 + 3 dose escalation schedule will be used for all escalations. The selinexor will be taken starting 1 week for dose escalation at 60, 80, 100, 40 mg once per week every 3 weeks before the first docetaxel infusion. The docetaxel will be given the first day of each 21 day cycle at the dose of either 60 or 75 mg/m2 every 3 weeks.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

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