Phase 2 Trial of Selinexor (KPT-330) for Metastatic Triple Negative Breast Cancer (TNBC)

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02402764
• Collaborator: Karyopharm Therapeutics Inc (Industry)
• Enrollment: 10
• Location: 1
• Arm: 1
• Actual Duration (Months): 46.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose of this study is to see whether the combination of selinexor (KPT-330) can help people with triple negative breast cancer (TNBC). Researchers also want to study the safety and tolerability of Selinexor in TNBC patients.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Selinexor	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Investigator-Initiated Phase 2 Clinical Trial of Selinexor (KPT-330) for the Treatment of Metastatic Triple Negative Breast Cancer
• Actual Study Start Date: Jul 8, 2015
• Actual Primary Completion Date: Mar 10, 2016
• Actual Study Completion Date: Jun 6, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Selinexor Treatment Screening period (which may last up to 28 days), followed by Selinexor treatment for qualified participants. During the treatment period, participants will undergo physical examination every 2 weeks until Cycle 6 Day 1 (C6D1), and then every 4 weeks and assessment of tumor response every 8 weeks. Participants will be treated until progression of disease or the development of unacceptable toxicities. All participants will then undergo a final visit (end of treatment visit).

Drug: Selinexor; Participants will receive selinexor twice weekly on Monday/Wednesday, Tuesday/Thursday or Wednesday/Friday of Weeks 1, 2 and 3 of each 4-week cycle. Selinexor will not be taken during Week 4. One cycle is defined as 28 days or 6 doses. The starting dose for this trial is 60 mg (flat dose as long as their dose-based body surface area (BSA) analysis does not exceed 70 mg/m^2).; Other Names: KPT-330 Selective Inhibitor of Nuclear Export (SINE)

Outcome Measures

Primary Outcome Measures

1. Clinical Benefit Rate [Up to 10 months]

   Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) ≥ 12 weeks of selinexor in patients with triple negative breast cancer (TNBC), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Secondary Outcome Measures

1. Best Overall Response (OR) [Up to 10 months]

   The best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.

2. Duration of Overall Response [Up to 10 months]

   The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) or death. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented or death.

3. Progression-Free Survival (PFS) [Up to 10 months]

   Median time to progression. Progression-free survival is defined as time elapsed from the beginning of study treatment to the first documentation of radiologic progression as defined by standard RECIST criteria or death.

4. Overall Survival (OS) [End of post-treatment 12 month follow-up, up to 24 months per participant]

   Overall survival, defined as the time from randomization to death from any cause.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed triple negative breast cancer (TNBC), defined as negative immunohistochemical staining for estrogen and progesterone receptors (≤5% of nuclei positive by IHC) and receptor tyrosine-protein kinase erbB-2 (HER2) negative (IHC 0-1+ or HER2-neu negative according to American Society of Clinical Oncology; College of American Pathologists (ASCO-CAP) HER2 Test Guideline Recommendations)

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

• Body surface area ≥1.4 m^2

• Age ≥18 years

• Estimated life expectancy of >3 months at study entry

• TNBC must be either locally recurrent or metastatic. Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent.

• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

• Documented disease progression at study entry

• Must have received at least 1 chemotherapy regimens in the setting of metastatic disease

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

• Adequate hematological function: Absolute neutrophil count (ANC) > 1500/mm^{3, platelets count >100,000mm}3

• Adequate hepatic function within 14 days prior to Cycle 1 Day 1 (C1D1): 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) and aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5 x ULN. In the case of known (radiological and/or biopsy documented) liver metastasis, AST/ALT ≤5.0 times ULN is acceptable.

• Amylase and lipase ≤ 1.5 x ULN

• Adequate renal function within 14 days prior to C1D1: estimated creatinine clearance of ≥ 30 mL/min

• Women of child-bearing potential (WOCBP) must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male participants must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. For both male and female participants, effective methods of contraception must be used throughout the study and for 3 months following the last dose. To be considered of non-childbearing potential, postmenopausal women must be amenorrheic for at least 12 months naturally (not in the setting of post chemotherapy) or participants must be surgically sterile.

• Must have received prior anthracycline and taxane therapy unless clinically contraindicated

Exclusion Criteria:

• Significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the participant's ability to tolerate this therapy

• Women who are pregnant or lactating

• Radiation, chemotherapy, or immunotherapy or any other approved anticancer therapy ≤2 weeks prior to cycle 1 day 1

• Major surgery within 4 weeks before Day 1

• Unstable cardiovascular function: Electrocardiogram (ECG) abnormalities requiring treatment, or congestive heart failure (CHF) of New York Hearth 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. Potential participants with controlled infection or on prophylactic antibiotics are permitted in the study.

• Known history of HIV

• Known active hepatitis A, B, or C infection that requires treatment

• Any underlying condition that would significantly interfere with the absorption of an oral medication

• Grade >2 peripheral neuropathy at baseline (within 14 days prior to cycle 1 day 1)

• Participation in an investigational anti-cancer study within 3 weeks prior to Cycle 1 Day 1

• Coagulation problems and active major bleeding within 4 weeks prior to C1D1 (peptic ulcer, epistaxis, spontaneous bleeding)

• Active central nervous system (CNS) malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months.

• Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to Cycle 1 Day 1 or radio-immunotherapy ≤ 4 weeks prior to Cycle 1 Day 1

• Have not recovered to Grade ≤ 1 or to their baseline from clinically significant adverse effects

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute
• Karyopharm Therapeutics Inc

Investigators

• Principal Investigator: Hyo S. Han, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT02402764
• Other Study ID Numbers: MCC-18150
• First Posted: Mar 30, 2015
• Last Update Posted: Sep 11, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: Triple Negative Breast Cancer (TNBC); Breast - Female; Breast - Male; Metastatic Triple Negative Breast Cancer; Receptor Tyrosine-protein Kinase erbB-2 (HER2) Negative; Erythroblastosis virus oncogene B (erbB)
• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at Moffitt Cancer Center between July 2015 and January 2016.

Arm/Group Title	Selinexor Treatment
Arm/Group Description	Ten patients were treated with oral selinexor 60 mg twice per week (on days 1 and 3) on a schedule of 3 weeks on and 1 week off, each four-week cycle.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Selinexor Treatment
Arm/Group Description	Ten patients were treated with oral selinexor 60 mg twice per week (on days 1 and 3) on a schedule of 3 weeks on and 1 week off, each four-week cycle.
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 70%
>=65 years	3 30%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	10 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Benefit Rate
Description	Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) ≥ 12 weeks of selinexor in patients with triple negative breast cancer (TNBC), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame	Up to 10 months

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Selinexor Treatment
Arm/Group Description	Ten patients were treated with oral selinexor 60 mg twice per week (on days 1 and 3) on a schedule of 3 weeks on and 1 week off, each four-week cycle.
Measure Participants	10
Complete Response	0 0%
Partial Response	0 0%
Stable Disease	3 30%
Progressive Disease	7 70%

2. Secondary Outcome

Title	Best Overall Response (OR)
Description	The best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.
Time Frame	Up to 10 months

Outcome Measure Data

Analysis Population Description

Participants with Complete Response or Partial Response

Arm/Group Title	Selinexor Treatment
Arm/Group Description	Ten patients were treated with oral selinexor 60 mg twice per week (on days 1 and 3) on a schedule of 3 weeks on and 1 week off, each four-week cycle.
Measure Participants	0

3. Secondary Outcome

Title	Duration of Overall Response
Description	The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) or death. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented or death.
Time Frame	Up to 10 months

Outcome Measure Data

Analysis Population Description

Participants with Complete Response or Partial Response

Arm/Group Title	Selinexor Treatment
Arm/Group Description	Ten patients were treated with oral selinexor 60 mg twice per week (on days 1 and 3) on a schedule of 3 weeks on and 1 week off, each four-week cycle.
Measure Participants	0

4. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Median time to progression. Progression-free survival is defined as time elapsed from the beginning of study treatment to the first documentation of radiologic progression as defined by standard RECIST criteria or death.
Time Frame	Up to 10 months

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Selinexor Treatment
Arm/Group Description	Ten patients were treated with oral selinexor 60 mg twice per week (on days 1 and 3) on a schedule of 3 weeks on and 1 week off, each four-week cycle.
Measure Participants	10
Median (95% Confidence Interval) [months]	1.0

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival, defined as the time from randomization to death from any cause.
Time Frame	End of post-treatment 12 month follow-up, up to 24 months per participant

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Selinexor Treatment
Arm/Group Description	Ten patients were treated with oral selinexor 60 mg twice per week (on days 1 and 3) on a schedule of 3 weeks on and 1 week off, each four-week cycle.
Measure Participants	10
Median (95% Confidence Interval) [months]	6.0

Adverse Events

Time Frame	10 months
Arm/Group Title	Selinexor Treatment
Arm/Group Description	Ten patients were treated with oral selinexor 60 mg twice per week (on days 1 and 3) on a schedule of 3 weeks on and 1 week off, each four-week cycle.
All Cause Mortality
	Selinexor Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Selinexor Treatment
	Affected / at Risk (%)	# Events
Total	3/10 (30%)
Cardiac disorders
Sinus tachycardia	1/10 (10%)	1
Eye disorders
Blurred vision	1/10 (10%)	1
Nervous system disorders
Memory impairment	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/10 (20%)	2
Other (Not Including Serious) Adverse Events
	Selinexor Treatment
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Anemia	1/10 (10%)	1
Eye disorders
Blurred vision	4/10 (40%)	4
Gastrointestinal disorders
Constipation	5/10 (50%)	5
Vomiting	5/10 (50%)	5
Nausea	3/10 (30%)	3
Diarrhea	2/10 (20%)	2
Abdominal pain	1/10 (10%)	1
Bloating	1/10 (10%)	1
General disorders
Fatigue	3/10 (30%)	5
Fever	1/10 (10%)	1
Gait disturbance	1/10 (10%)	1
Irritability	1/10 (10%)	1
Non-cardiac chest pain	1/10 (10%)	1
Infections and infestations
Sinusitis	1/10 (10%)	2
Injury, poisoning and procedural complications
Fall	1/10 (10%)	1
Investigations
Platelet count decreased	3/10 (30%)	6
Alanine aminotransferase increased	1/10 (10%)	1
Blood bilirubin increased	1/10 (10%)	2
Investigations - Other, specify	1/10 (10%)	1
Metabolism and nutrition disorders
Anorexia	4/10 (40%)	4
Hypocalcemia	2/10 (20%)	2
Hypophosphatemia	2/10 (20%)	3
Hyperglycemia	1/10 (10%)	1
Hypermagnesemia	1/10 (10%)	1
Hypomagnesemia	1/10 (10%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/10 (20%)	2
Back pain	1/10 (10%)	1
Flank pain	1/10 (10%)	1
Nervous system disorders
Dysgeusia	2/10 (20%)	2
Dizziness	1/10 (10%)	1
Encephalopathy	1/10 (10%)	1
Headache	1/10 (10%)	1
Renal and urinary disorders
Urinary incontinence	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/10 (20%)	2
Cough	2/10 (20%)	2
Nasal congestion	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Pruritus	1/10 (10%)	1
Rash maculo-papular	1/10 (10%)	1
Vascular disorders
Hot flashes	2/10 (20%)	2
Hypertension	1/10 (10%)	1
Hypotension	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

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.