Selinexor in Treating Patients With Relapsed Small Cell Lung Cancer

• Sponsor: Erin Bertino (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02351505
• Collaborator: Karyopharm Therapeutics Inc (Industry)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 10
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well selinexor work in treating patients with small-cell lung cancer that has returned after a period of improvement. One specific way cancer cells continue to grow is by getting rid of certain proteins called "tumor suppressor proteins: that would normally cause cancer cells to die. Selinexor works by trapping "tumor suppressing proteins" within the cell and may cause the cancer cells to die or stop growing.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Small Cell Lung Carcinoma	Drug: Selinexor; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the efficacy of single agent selinexor as measured by progression free survival (PFS) in patients with relapsed chemotherapy-sensitive small cell lung cancer.

SECONDARY OBJECTIVES:

1. To evaluate the objective tumor response rate and disease control rate as determined by radiographic response.

2. To evaluate the overall survival (OS) in patients with relapsed small cell lung cancer.

3. To evaluate safety and tolerability of single agent selinexor in these patient populations.

4. Comparison between each patient's time to progression (TTP) on selinexor with the TTP of his/her previous therapy(ies).

5. To evaluate correlative endpoints including tumor biopsy and analysis of secreted factors, leukocyte ribonucleic acid (RNA) analysis.

TERTIARY OBJECTIVES:

1. Analysis of secreted factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF]).

2. Tumor biopsy (baseline and cycle 2).

OUTLINE:

Patients receive selinexor orally (PO) twice weekly. 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 1 year, and then every 6 months thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Investigator-Sponsored Phase 2 Study of Single Agent Selinexor (KPT-330) in Patients With Relapsed Small Cell Lung Cancer
• Study Start Date: May 1, 2015
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (selinexor) Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: Selinexor; Given PO; Other Names: CRM1 Nuclear Export Inhibitor KPT-330 KPT-330 Selective Inhibitor of Nuclear Export KPT-330 SINE KPT-330 ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Other Names: pharmacological studies

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [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 4 years]

   Estimated by the method of Kaplan and Meier for each cohort. Appropriate one-sided 90% confidence boundary will also be calculated for the final test Kaplan-Meyer test statistic at 12 weeks.

Secondary Outcome Measures

1. Objective Response Rate (Complete Response [CR] or Partial Response [PR]) by RECIST [Up to 4 years]

   The overall response rate will be calculated as the number of PRs and CRs divided by the total number of evaluable patients. Estimates will be accompanied by exact binomial confidence intervals as well.

2. Disease Control Rate (CR, PR, and Stable Disease) [Up to 4 years]

   Estimates will be accompanied by exact binomial confidence intervals.

3. Overall Survival [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 4 years]

   Kaplan-Meier curves will be used to estimate overall survival. Consider Cox proportional hazards models to explore a limited set of confounding factors.

4. Frequency of Adverse Events Defined as Adverse Events That Are Classified as Either Not Related, Possibly, Probably, or Definitely Related to Study Treatment as Per NCI CTCAE v4.0 [Up to 4 years]

   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. In addition, review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing.

5. Incidence of Severe (Grade 3+) Adverse Events or Toxicities as Per NCI CTCAE v4.0 [Up to 4 years]

   The incidence of severe (grade 3+) adverse events or toxicities will be described.

6. Tolerability of the Regimen Assessed Through Number of Patients Who Required Dose Modifications and/or Dose Delays [Up to 4 years]

7. Proportion of Patients Who go Off Treatment Due to Adverse Reactions or Even Those Who Refuse Further Treatment for Lesser Toxicities That Inhibit Their Willingness to Continue Participation on the Trial [Up to 4 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent in accordance with federal, local, and institutional guidelines

• Patients should have estimated life expectancy of > 3 months at study entry

• Patients with relapsed small cell lung cancer - 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 no more than 2 prior chemotherapy regimens; the regimen(s) may have included biological, molecularly targeted or immune therapies; patients with primary refractory disease (i.e., those patients with progressive disease on first line chemotherapy) and patients with disease relapse within 90 days of completion of initial chemotherapy (chemotherapy resistant) are excluded; patients with limited stage small cell lung cancer (SCLC) and systemic relapse who are not felt to be candidates for repeat platinum-based chemotherapy at relapse are eligible for enrollment

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Absolute neutrophil count (ANC) > 1000/mm^3

• Platelet count > 75,000 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

• Albumin >= 3.0 mg/dl

• Estimated creatinine clearance of >= 30 mL/min, calculated using the formula of Cockroft and Gault

• Amylase =< 1.5 x ULN

• Lipase =< 1.5 x ULN

• Alkaline phosphatase limit =< 2.5 x ULN

• Female patients of childbearing 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; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose

• Resolution to grade =< 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (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)

• Available archival tumor tissue or willingness to undergo repeat biopsy is required at trial initiation

Exclusion Criteria:

• Primary refractory disease (progressive disease on initial platinum based chemotherapy) or chemotherapy-resistant disease (disease progression within 90 days of completion of initial chemotherapy)

• Patients who are pregnant or lactating

• Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =< 2 weeks prior to cycle 1 day 1; any clinical trial therapy (including investigational anti-cancer study) =< 3 weeks prior to cycle 1 day 1

• Prior treatment with selinexor

• Major surgery within 3 weeks before day 1

• Unstable cardiovascular function:

• Electrocardiogram (ECG) abnormalities requiring treatment, or

• Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3

• Myocardial infarction (MI) within 3 months

• Symptomatic ischemia or angina

• 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)

• Serious psychiatric or medical conditions that could interfere with treatment

• History of seizures, movement disorders or cerebrovascular accident within the past 5 years prior to cycle 1 day 1

• Concurrent therapy with approved or investigational anticancer therapeutic other than steroids

• Patients with > 3 liver metastases at time of enrollment

• Patients with coagulation problems and active bleeding in the last month (peptic ulcer, epistaxis, spontaneous bleeding)

• Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications

• Patients who are severely underweight (body mass index [BMI] less than 17) or patients with a body surface area (BSA) < 1.4 m^2 as calculated per Dubois 1916 or Mosteller 1987

• Uncontrolled brain metastases or leptomeningeal involvement; patients with brain metastases are permitted if they have received appropriate therapy and demonstrated control of the brain metastases or leptomeningeal disease 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])

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Erin Bertino
• Karyopharm Therapeutics Inc

Investigators

• Principal Investigator: Erin Bertino, MD, Ohio State University Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The Jamesline

Publications

None provided.

• Responsible Party: Erin Bertino, Principal Investigator, Ohio State University Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT02351505
• Other Study ID Numbers: OSU-14136; NCI-2014-02489
• First Posted: Jan 30, 2015
• Last Update Posted: May 16, 2016
• Last Verified: May 1, 2016

• Keywords provided by Erin Bertino, Principal Investigator, Ohio State University Comprehensive Cancer Center: Small Cell Lung Cancer
• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma

Study Results

Participant Flow

Arm/Group Title	Arm A: Selinexor (KPT-330)
Arm/Group Description	Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Pharmacological Study: Correlative studies
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Arm A: Selinexor (KPT-330)
Arm/Group Description	Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	1 100%
Sex: Female, Male (Count of Participants)
Female	1 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	1 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (patients) [Number]
United States	1

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Description	Estimated by the method of Kaplan and Meier for each cohort. Appropriate one-sided 90% confidence boundary will also be calculated for the final test Kaplan-Meyer test statistic at 12 weeks.
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 4 years

Outcome Measure Data

Analysis Population Description

Unable to analyze data due to only 1 patient being enrolled on the study

Arm/Group Title	Arm A: Selinexor (KPT-330)
Arm/Group Description	Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Pharmacological Study: Correlative studies
Measure Participants	0

2. Secondary Outcome

Title	Objective Response Rate (Complete Response [CR] or Partial Response [PR]) by RECIST
Description	The overall response rate will be calculated as the number of PRs and CRs divided by the total number of evaluable patients. Estimates will be accompanied by exact binomial confidence intervals as well.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Unable to analyze data due to only 1 patient being enrolled on the study

Arm/Group Title	Arm A: Selinexor (KPT-330)
Arm/Group Description	Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

3. Secondary Outcome

Title	Disease Control Rate (CR, PR, and Stable Disease)
Description	Estimates will be accompanied by exact binomial confidence intervals.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Unable to analyze data due to only 1 patient being enrolled on the study

Arm/Group Title	Arm A: Selinexor (KPT-330)
Arm/Group Description	Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

4. Secondary Outcome

Title	Overall Survival
Description	Kaplan-Meier curves will be used to estimate overall survival. Consider Cox proportional hazards models to explore a limited set of confounding factors.
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 4 years

Outcome Measure Data

Analysis Population Description

Unable to analyze data due to only 1 patient being enrolled on the study

Arm/Group Title	Arm A: Selinexor (KPT-330)
Arm/Group Description	Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

5. Secondary Outcome

Title	Frequency of Adverse Events Defined as Adverse Events That Are Classified as Either Not Related, Possibly, Probably, or Definitely Related to Study Treatment as Per NCI CTCAE v4.0
Description	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. In addition, review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Unable to analyze data due to only 1 patient being enrolled on the study

Arm/Group Title	Arm A: Selinexor (KPT-330)
Arm/Group Description	Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

6. Secondary Outcome

Title	Incidence of Severe (Grade 3+) Adverse Events or Toxicities as Per NCI CTCAE v4.0
Description	The incidence of severe (grade 3+) adverse events or toxicities will be described.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Selinexor (KPT-330)
Arm/Group Description	Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	1
Fatigue	100
Generalized muscle weakness	100
Bilateral Lower Extrem Edema	100
Hyperglycemia	100
Hyponatremia	100

7. Secondary Outcome

Title	Tolerability of the Regimen Assessed Through Number of Patients Who Required Dose Modifications and/or Dose Delays
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Unable to analyze data due to only 1 patient being enrolled on the study

Arm/Group Title	Arm A: Selinexor (KPT-330)
Arm/Group Description	Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

8. Secondary Outcome

Title	Proportion of Patients Who go Off Treatment Due to Adverse Reactions or Even Those Who Refuse Further Treatment for Lesser Toxicities That Inhibit Their Willingness to Continue Participation on the Trial
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Unable to analyze data due to only 1 patient being enrolled on the study

Arm/Group Title	Arm A: Selinexor (KPT-330)
Arm/Group Description	Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	Frequency and severity of adverse events and tolerability of the regimen were collected and summarized by descriptive statistics for each of the disease cohorts. As per NCI CTCAE v4.0, the term toxicity is defined as adverse events that are classified as either not related, possibly, probably, or definitely related to study treatment.
Arm/Group Title	Arm A: Selinexor (KPT-330)
Arm/Group Description	Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Arm A: Selinexor (KPT-330)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arm A: Selinexor (KPT-330)
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Arm A: Selinexor (KPT-330)
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Blood and lymphatic system disorders
Anemia	1/1 (100%)	1
Eye disorders
Eye disorder-decreased visual acuity	1/1 (100%)	1
Fall	1/1 (100%)	1
Gastrointestinal disorders
Anorexia	1/1 (100%)	1
Nausea	1/1 (100%)	1
General disorders
Fatigue	1/1 (100%)	1
Edema	1/1 (100%)	1
Infections and infestations
Urinary tract infection	1/1 (100%)	1
Investigations
Activated PTT prolonged	1/1 (100%)	1
Platelet count decreased	1/1 (100%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/1 (100%)	1
Hypoalbuminemia	1/1 (100%)	1
Hypomagnesemia	1/1 (100%)	1
Hyponatremia	1/1 (100%)	1
Musculoskeletal and connective tissue disorders
Generalized Muscle Weakness	1/1 (100%)	1
Myalgias	1/1 (100%)	1
Nervous system disorders
Concentration impairment	1/1 (100%)	1
Depressed level of conciousness	1/1 (100%)	1
Headache	1/1 (100%)	1
Renal and urinary disorders
Hematuria	1/1 (100%)	1
Respiratory, thoracic and mediastinal disorders
Wheezing	1/1 (100%)	1

Limitations/Caveats

Trial was closed early due to slow accrual.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.