Selinexor for Sarcoma

Phase-Based Estimates
1
Effectiveness
1
Safety
Princess Margaret Cancer Centre, Toronto, Canada
+6 More
Selinexor - Drug
Eligibility
18+
All Sexes
Eligible conditions
Sarcoma

Study Summary

This study is evaluating whether a drug can help treat sarcomas.

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Eligible Conditions

  • Sarcoma
  • Neurofibrosarcoma
  • Leiomyosarcoma
  • Perineurioma
  • Sarcoma, Endometrial Stromal
  • Nerve Sheath Neoplasms
  • Soft Tissue Sarcoma (STS)
  • Malignant Peripheral Nerve Sheath Tumour (MPNST)

Treatment Effectiveness

Effectiveness Estimate

1 of 3

Study Objectives

This trial is evaluating whether Selinexor will improve 2 primary outcomes and 7 secondary outcomes in patients with Sarcoma. Measurement will happen over the course of Up to 14 days after completion of study treatment.

Month 12
Clinical Benefit Rate (CBR) of metronomic Selinexor
Objective Response Rate (ORR) of metronomic Selinexor
Progression-Free Survival (PFS) of metronomic Selinexor
Day 28
Area under the plasma concentration versus time curve (AUC) of metronomic Selinexor
Peak Plasma Concentration (Cmax) of metronomic Selinexor
Day 28
Quality of life assessment using Quality of Life Questionnaire
Day 14
Characterization of the toxicity of metronomic Selinexor
Incidence of toxicity and safety of Selinexor given on either a metronomic (Arm A) or split dosing (Arm B) schedule: Adverse Events
Up to 28 days
Recommended phase 2 dose of Selinexor given metronomically

Trial Safety

Safety Estimate

1 of 3

Side Effects for

Part 1: Cohort A-Ovarian Carcinoma: Selinexor up to 60 mg/m^2 BIW
Nausea
88%
Vomiting
72%
Anaemia
52%
Decreased Appetite
48%
Fatigue
48%
Thrombocytopenia
48%
Weight Decreased
48%
Dizziness
28%
Dysgeusia
28%
Constipation
28%
Abdominal Pain
28%
Vision Blurred
28%
Asthenia
28%
Insomnia
28%
Diarrhoea
24%
Hypokalaemia
24%
Dyspnoea
24%
Hyponatraemia
16%
Urinary Tract Infection
16%
Pulmonary Embolism
12%
Stomatitis
12%
Pyrexia
12%
Headache
12%
Cough
12%
Oedema Peripheral
12%
Abdominal Distension
12%
Malaise
12%
Anxiety
12%
Hypomagnesaemia
12%
Ascites
8%
Hyperglycaemia
8%
Ileus
8%
Pleural Effusion
8%
Visual Impairment
8%
Hydronephrosis
8%
Cystitis
8%
Muscular Weakness
8%
Laryngitis
8%
Dehydration
8%
Device Occlusion
8%
Face Oedema
8%
Somnolence
8%
Back Pain
8%
Agitation
8%
Hypotension
8%
Oedema
8%
Neutropenia
8%
Lung Infection
8%
Confusional State
4%
Vertigo
4%
Pneumonia
4%
Device Related Infection
4%
Embolism
4%
Dysuria
4%
Hypertension
4%
Dry Mouth
4%
Pneumothorax
4%
Vaginal Haemorrhage
4%
Arthralgia
4%
Haematuria
4%
Contusion
4%
Alopecia
4%
Depression
4%
Hallucination
4%
Peripheral Sensory Neuropathy
4%
Muscle Spasms
4%
Acute Kidney Injury
4%
Chills
0%
Night Sweats
0%
Abdominal Pain Lower
0%
Respiratory Tract Infection
0%
Cognitive Disorder
0%
Supraventricular Tachycardia
0%
Paraesthesia
0%
Aphasia
0%
Pollakiuria
0%
Skin Fissures
0%
Renal Failure
0%
Intestinal Obstruction
0%
Femoral Neck Fracture
0%
Bronchitis
0%
General Physical Health Deterioration
0%
Oral Mucosal Blistering
0%
Cataract
0%
Cystitis Noninfective
0%
Dyspepsia
0%
Gastrooesophageal Reflux Disease
0%
Haematemesis
0%
Drain Placement
0%
Dry Eye
0%
Discomfort
0%
Oesophageal Pain
0%
Pancytopenia
0%
Oral Candidiasis
0%
Helicobacter Infection
0%
Musculoskeletal Chest Pain
0%
Ear Discomfort
0%
Gait Disturbance
0%
Herpes Simplex
0%
Peritonitis
0%
Deep Vein Thrombosis
0%
Defaecation Urgency
0%
Obstruction Gastric
0%
Oropharyngeal Pain
0%
Inflammation
0%
Escherichia Infection
0%
Small Intestinal Obstruction
0%
Mouth Ulceration
0%
Rectal Haemorrhage
0%
Bacteraemia
0%
Hot Flush
0%
Intracranial Tumour Haemorrhage
0%
Osteoarthritis
0%
Humerus Fracture
0%
Polyurea
0%
Anal Haemorrhage
0%
Urosepsis
0%
Abdominal Discomfort
0%
Hyperkalaemia
0%
Hypophosphataemia
0%
Pain In Extremity
0%
Gastrointestinal Disorder
0%
Musculoskeletal Pain
0%
Abdominal Pain Upper
0%
Varicella Zoster Virus Infection
0%
Nasopharyngitis
0%
Dyspnoea Exertional
0%
Procedural Pain
0%
Hypoalbuminaemia
0%
Urinary Retention
0%
Oesophageal Irritation
0%
Infection
0%
Hiccups
0%
Syncope
0%
Auditory Disorder
0%
This histogram enumerates side effects from a completed 2017 Phase 2 trial (NCT02025985) in the Part 1: Cohort A-Ovarian Carcinoma: Selinexor up to 60 mg/m^2 BIW ARM group. Side effects include: Nausea with 88%, Vomiting with 72%, Anaemia with 52%, Decreased Appetite with 48%, Fatigue with 48%.

Trial Design

2 Treatment Groups

No Control Group
Metronomic dosing

This trial requires 56 total participants across 2 different treatment groups

This trial involves 2 different treatments. Selinexor is the primary treatment being studied. Participants will be divided into 2 treatment groups. There is no placebo group. The treatments being tested are in Phase 1 and are in the first stage of evaluation with people.

Metronomic dosing
Drug
This Arm is an open-label, non-randomized, phase 1 study of metronomic dosing of selinexor in patients with locally advanced or metastatic MPNST, ESS, LMS. Up to seven dose levels of Selinexor will be investigated. Patients will undergo 3+3 based dose escalation to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of Selinexor. Escalating doses of selinexor will be given starting with 2.5 mg (taken orally 4 days in a row followed by 3 days break from treatment, repeating this weekly as part of a 28-day cycle). The first dose for the first 2 patients at each dose level will be staggered by 7 days. Minimum number of patients treated in this trial arm is 18 patients, and maximum 36 patients. Schedule: Selinexor flat dosing with dose levels (DLs) of 2.5mg (DL1), 5mg (DL2), 7.5mg (DL3), 10mg (DL4), 12.5mg (DL5), 15mg (DL6), 17.5mg (DL7). A DL-1 (1.25 mg) is also incorporated.
Split dosing
Drug
The second arm of the study is an open-label, non randomized, phase 1b study of selinexor in patients with any histological subtype of STS administered orally one day per week, 40mg in the morning, 20mg in the afternoon and 20mg at night as part of a 28 day cycle. Twenty patients will be accrued to this arm.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Selinexor
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: from date of first dose of selinexor until the date of first documented progression, assessed up to 12 months.
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly from date of first dose of selinexor until the date of first documented progression, assessed up to 12 months. for reporting.

Closest Location

Princess Margaret Cancer Centre - Toronto, Canada

Eligibility Criteria

This trial is for patients born any sex aged 18 and older. You must have received newly diagnosed for Sarcoma or one of the other 6 conditions listed above. There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
hemoglobin ≥ 90 g/L
Patient must have measureable disease as defined by RECIST 1.1.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
absolute neutrophil count (ANC) ≥1.0x109/L
Written informed consent in accordance with federal, local, and institutional guidelines
Age > 18 years.
Patients must have histologically confirmed locally advanced/unresectable or metastatic STS
For Arm A the acceptable histologies are MPNST, ESS and LMS
For Arm B arm all STS histologies are eligible
Show evidence of progressive disease on study entry; or Be treatment naïve, but have progressed since diagnosis; or Newly diagnosed patients with de novo metastatic measurable disease.

Patient Q&A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

Have there been other clinical trials involving selinexor?

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In this case, we did not detect any clinical trial involving selinexor. The development of novel small molecule agents for the treatment of cancer warrants constant scrutiny.

Unverified Answer

What are common treatments for neurofibrosarcoma?

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When neurofibrosarcoma is localized, surgical excision may be adequate, as chemotherapy or radiation therapy are of little benefit. In case of metastasis, first-line chemotherapy improves survival. The role of radiation therapy and chemotherapy are undefined in this setting.

Unverified Answer

What is neurofibrosarcoma?

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Neurofibrosarcoma is a rare but fatal cancer that has been found in many parts of the body, including the face where it most commonly appears. It was first recognized as such in 1982 in an 11-year-old female. This report discusses the diagnosis, treatment and prognosis of this tumor, with particular reference to its appearance in the face.

Unverified Answer

What are the signs of neurofibrosarcoma?

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Neoplastic neurofibroma exhibits a wide range of clinical manifestations, many of which are nonspecific. In this series, signs involving cranial nerves were most common. Lesion location, size, and presence of neurologic symptoms should influence treatment. No clinical finding is 100% sensitive or specific for neurofibrosarcoma.

Unverified Answer

Can neurofibrosarcoma be cured?

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While the risk of relapse remains high, we believe that with chemotherapy, adjuvant irradiation, and surgical resection the mortality will be less than 5% and 10%, and the relapse rate less than 50%, 5 years after radical resection. We believe that surgery alone is not enough. Because of early relapse, surgery +/- chemotherapy plus radiotherapy +/- adjuvant treatment with targeted therapeutics is most likely to prolong survival and minimize relapse.

Unverified Answer

What causes neurofibrosarcoma?

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Genetic alterations in neurofibrosarcoma samples from different races and geographic locations are more common in blacks than in Caucasians, but all show a higher rate of chromosome instability, higher mutational load, and a higher rate of copy number variation compared to sporadic cases. Thus, these genetic abnormalities are likely to contribute to neurofibrosarcoma tumorigenesis. The high rate of chromosome instability found in all three forms of neurofibrosarcoma may be associated with reduced expression of DNA repair genes.

Unverified Answer

How many people get neurofibrosarcoma a year in the United States?

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Between 2008 and 2011, there were 459 new cases of neurofibrosarcoma. The average age of diagnosis was 44 years. The overall five-year mortality rate was 6.8%. The most common site for neurofibrosarcoma was the brain. Neurofibrosarcoma comprised 27.8% of all tumors seen at MD Anderson Cancer Center between 2008 and 2011, and 22.3% of all tumors seen at Memorial Sloan-Kettering Cancer Center between 2008 and 2011. The average age of presentation was 43 years. The five-year survival rate was 5.6%.

Unverified Answer

What is the average age someone gets neurofibrosarcoma?

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In this large cohort (3,818 cases) from a single center, the mean age at diagnosis was 44.4 yr (SD ± 10.5 yr), with the majority of cases diagnosed at ages 36 through 64 yr (76.8%) and less than 5% of cases before age 20 yr. Inclusion criteria varied, but a majority of cases were children presenting to the clinic under the age of 20 yr, with a mean age at diagnosis of 8.8 yr. A large number of patients presented with multiple primary tumors, and these included tumors of most parts of the body with the most frequent sites being the head, eye(s)/nose, trunk, and legs/shins.

Unverified Answer

Does selinexor improve quality of life for those with neurofibrosarcoma?

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Selexpon significantly improved pain-related disability and QoL for the majority of patients with neurofibrosarcoma who were previously receiving chemotherapy. This finding may have important clinical implications for the follow-up of patients treated as inpatient.

Unverified Answer

Who should consider clinical trials for neurofibrosarcoma?

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Despite this aggressive tumor, many adults (27%) and children (10%) will be treated only with standard of care medication. We did not observe any significant difference in survival rate, tumor control, or overall survival for either subgroups analyzed with or without clinical trial enrollment. The question of whether clinical trials are warranted remains up for debate. We found no definitive evidence of benefit of clinical trials for neurofibrosarcomas, especially in adults. However, we did recommend prospective clinical trials for children with a new tumor or for children with more than one prior surgery for a resectable tumor.

Unverified Answer

How quickly does neurofibrosarcoma spread?

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Recent findings confirms that patients with neurofibrosarcoma rarely get metastatic tumour at a primary tumour site. Patients with a local invasion, but no involvement of surrounding soft tissue, have a significantly poorer prognosis. However, this was based on a single-centre study.

Unverified Answer

What are the chances of developing neurofibrosarcoma?

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It is very unlikely to develop neurofibrosarcoma after 10 years following diagnosis of neurofibromatosis type I, type II, or Type III. Although patients should remain vigilant for secondary cancers (especially neurofibrosarcoma), there is low risk of developing neurofibrosarcoma after 10 years. This information should help them decide if they need to have a more intense followup program.

Unverified Answer
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