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Selinexor and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Lung Cancer

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: NCT02536495
Recruitment Status : Withdrawn (PI decision due to funding support)
First Posted : September 1, 2015
Last Update Posted : October 30, 2015
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
Erin Bertino, Ohio State University Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE August 27, 2015
First Posted Date  ICMJE September 1, 2015
Last Update Posted Date October 30, 2015
Study Start Date  ICMJE September 2015
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 27, 2015)
Progression free survival [ Time Frame: Time from the date of study registration to the date of disease progression or to the date of last observation when no event (disease progression) has occurred, assessed up to 3 years ]
PFS will be estimated by the method of Kaplan and Meier (KM). Appropriate one-sided 90% confidence boundary will also be calculated for the final test KM test statistic at 12 weeks.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2015)
  • Disease control rate (Complete Response + Partial Response + stable disease) [ Time Frame: Up to 1 year ]
    An analysis of disease control rate will be performed. These estimates will be accompanied by exact binomial confidence intervals as well.
  • Incidence of adverse events, graded according to the National Cancer Institute CTCAE version 4.03 [ Time Frame: Up to 1 year ]
    Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized by descriptive statistics for each of the disease cohorts. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
  • Objective response rate (complete response [CR] or partial response [PR] by RECIST) [ Time Frame: Up to 1 year ]
    Those who achieve PR or CR will be considered responses and the overall response rate will be calculated as the number of PRs and CRs divided by the total number of evaluable patients. These estimates will be accompanied by exact binomial confidence intervals as well.
  • Overall survival [ Time Frame: Date of study registration to the date of event (i.e., death) or the date of last follow-up if no event has occurred at their last evaluation, assessed up to 3 years ]
    Kaplan-Meier curves will be used to estimate overall survival. Cox proportional hazards models will be further considered to explore a limited set of confounding factors.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 27, 2015)
Changes in tumor suppressor protein expression levels [ Time Frame: Baseline to up to course 2, day 1 ]
Tumor biopsies before and after therapy will be evaluated to assess baseline expression of tumor suppressor proteins and how change in these proteins may correspond with clinical outcomes of interest. Markers will be summarized by descriptive statistics overall and through stratified Kaplan Meier plots to explore differences in PFS. Generalized linear models will model changes in expression levels over time, with potential adjustment for confounding variables.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Selinexor and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Lung Cancer
Official Title  ICMJE An Investigator-Sponsored Phase 1/2 Study of Selinexor (KPT-330) and Docetaxel as Second Line Therapy in Patients With Relapsed Squamous Cell Lung Cancer
Brief Summary This phase I/II trial studies the side effects and best dose of selinexor and docetaxel and to see how well they work when given together in treating patients with squamous cell lung cancer that has come back or spread to other places in the body. Selinexor may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving selinexor together with docetaxel may work better in treating squamous cell lung cancer.
Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the toxicity and determine recommended phase II dose of the combination of docetaxel and selinexor. (Phase I) II. To evaluate the efficacy as measured by progression free survival (PFS) of docetaxel and selinexor in patients with recurrent/metastatic squamous cell lung cancer. (Phase I/II)

SECONDARY OBJECTIVES:

I. To evaluate the objective tumor response rate as determined by radiographic response.

II. To evaluated the disease control rate (complete response, partial responses, and stable disease).

III. To evaluate the overall survival (OS). IV. To evaluate the safety and tolerability of single agent selinexor.

TERTIARY OBJECTIVES:

I. Lung cancer genomics sequencing panel. II. Tumor biopsy (baseline and cycle 2). III. Plasma cytokine analysis, peripheral blood ribonucleic acid (RNA) analysis.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive docetaxel intravenously (IV) on day 1 and selinexor orally (PO) twice daily (BID) on days 1, 3, 7, 9, 13, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly for 3 months, every 3 months for 9 months, and then every 6 months thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Squamous Cell Lung Carcinoma
  • Stage IV Squamous Cell Lung Carcinoma
Intervention  ICMJE
  • Drug: Docetaxel
    Given IV
    Other Names:
    • RP56976
    • Taxotere
    • Taxotere Injection Concentrate
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacological Study
    Correlative studies
  • Drug: Selinexor
    Given PO
    Other Names:
    • CRM1 Nuclear Export Inhibitor KPT-330
    • KPT-330
    • Selective Inhibitor of Nuclear Export KPT-330
    • SINE KPT-330
Study Arms  ICMJE Experimental: Treatment (docetaxel, selinexor)
Patients receive docetaxel IV on day 1 and selinexor PO BID on days 1, 3, 7, 9, 13, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: Docetaxel
  • Other: Laboratory Biomarker Analysis
  • Other: Pharmacological Study
  • Drug: Selinexor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: October 28, 2015)
0
Original Estimated Enrollment  ICMJE
 (submitted: August 27, 2015)
52
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Patients with recurrent or metastatic squamous cell carcinoma of the lung - diagnosis must be histologically confirmed
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at the time of study entry
  • Objective evidence of disease progression on study entry
  • Prior systemic anticancer therapy: Patients will have received at least 1 platinum-based chemotherapy regimen, but no more than 2 cytotoxic chemotherapy regimens in the setting of recurrent or metastatic disease; the regimen(s) may have included biological, molecularly targeted or immune therapies; adjuvant chemotherapy is considered 1 cytotoxic chemotherapy regimen if the last administration occurred < 1 year prior to entry
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Absolute neutrophil count (ANC) > 1500/mm^3
  • Platelets count > 100,000 mm^3 and less than 1,000,000 mm^3
  • Total bilirubin < 2 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3 times ULN)
  • Alanine aminotransferase (ALT) < 2.5 times ULN; in the case of known (radiological and/or biopsy documented) liver metastasis, ALT < 5.0 times ULN is acceptable; patients with > 3 liver metastases at enrollment will be excluded
  • Estimated creatinine clearance of >= 30 mL/min, calculated using the formula of Cockcroft and Gault
  • Amylase =< 1.5 x ULN
  • Lipase =< 1.5 x ULN
  • Alkaline phosphatase limit =< 2.5 x ULN
  • Female patients of child-bearing potential must agree to use dual methods 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 child-bearing potential throughout the study and for three months following the last dose of selinexor
  • Resolution to grade =< 1 by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03) of all clinically significant toxic effects of prior anti-cancer therapy (with the exception neuropathy, which may be =< grade 2 within 14 days prior to cycle 1 day 1)

Exclusion Criteria:

  • Patients who are pregnant or lactating
  • Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =< 2 weeks prior to cycle 1 day 1
  • Prior treatment with selective inhibitor of nuclear export (SINE) inhibitor
  • Major surgery within four weeks before cycle 1, day 1
  • Unstable cardiovascular function:

    • Electrocardiography (ECG) abnormalities requiring treatment, or
    • Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3
    • Myocardial infarction (MI) within 3 months
  • Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
  • Known to be human immunodeficiency virus (HIV) seropositive
  • Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) RNA or hepatitis B surface antigen (HBsAg) (hepatitis B virus [HBV] surface antigen)
  • Any underlying condition that would significantly interfere with the absorption of an oral medication
  • Patients with markedly decreased visual acuity
  • Serious psychiatric or medical conditions that could interfere with treatment
  • Participation in an investigational anti-cancer study =< 3 weeks prior to cycle day 1
  • Concurrent therapy with approved or investigational anticancer therapeutic other than steroids
  • Patients with coagulation problems and active bleeding in the last month (peptic ulcer, epistaxis, spontaneous bleeding)
  • Uncontrolled brain metastases; patients with brain metastases are permitted if they have received appropriate therapy and demonstrated control of the brain metastases following therapy; patients with known brain metastases will require magnetic resonance imaging (MRI) brain to demonstrate disease control prior to enrollment (lack of symptom progression for two weeks off therapeutic doses of steroids, excluding chronic steroids used for control of chronic obstructive pulmonary disease [COPD])
  • Renal failure requiring hemodialysis or peritoneal dialysis
  • Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications
  • Patients who are severely underweight in the opinion of the investigator
  • Prior cancer diagnosis is allowed if patient is disease-free for >= 3 years, or disease free for < 3 years for treated basal cell/squamous cell skin cancer or in situ cervical cancer
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT02536495
Other Study ID Numbers  ICMJE OSU-14152
NCI-2015-01165 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Erin Bertino, Ohio State University Comprehensive Cancer Center
Study Sponsor  ICMJE Erin Bertino
Collaborators  ICMJE Karyopharm Therapeutics Inc
Investigators  ICMJE
Principal Investigator: Erin Bertino, MD Ohio State University Comprehensive Cancer Center
PRS Account Ohio State University Comprehensive Cancer Center
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP