LiposarcomaPhase 1NCT03880123
Selinexor in Combination With Ixazomib for the Treatment of Advanced Sarcoma
A Phase 1 study testing Selinexor and Ixazomib in people with Liposarcoma and Malignant Peripheral Nerve Sheath Tumors, run by Matthew Ingham at 1 site in United States.
Trial summary
The main purpose of this study is to establish a safe and tolerable dose combination (the "maximum tolerated dose") of selinexor and ixazomib when used together for the treatment of patients with certain types of advanced sarcoma. Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Liposarcoma, Malignant Peripheral Nerve Sheath Tumors, Alveolar Soft Part Sarcoma
- What is being tested?
- Selinexor and Ixazomib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2020to 24 Nov 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Signed written informed consent.
- Age ≥ 14 years
- Body surface area ≥ 1.2 m2
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Histologically confirmed de-differentiated liposarcoma, malignant peripheral nerve sheath tumor, alveolar soft part sarcoma or Ewing sarcoma. Liposarcomas with areas of well-differentiated disease are eligible if there is a biopsy-proven component of dedifferentiated liposarcoma. Pathology is reviewed at Columbia University Medical Center.
- Disease which is locally advanced and unresectable or metastatic. Disease which may be resected but with an associated level of morbidity deemed unacceptable by the treating clinician is considered eligible.
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- Measurable disease as assessed by RECIST criteria version 1.1.
- Progression on, or intolerance to, at least one prior systemic regimen for sarcoma (including systemic treatment used in the adjuvant or neoadjuvant settings). For alveolar soft part sarcoma and dedifferentiated liposarcoma, there is no upper limit on the number of prior therapies that may have been received. For Ewing sarcoma and malignant peripheral nerve sheath tumor, patients may have received no more than 3 prior lines of therapy (excluding systemic treatment used in the adjuvant or neoadjuvant settings).
- Acceptable organ and marrow function as defined below:
- Absolute neutrophil count (ANC) ≥ 1,500/mm3 Hemoglobin ≥ 8.5 g/dL Platelet count ≥ 100,000/mm3 Calculated creatinine clearance > 30 mL/min Total bilirubin ≤ 1.5 times upper limit of normal Aspartate Transaminase (AST) /Alanine Transaminase (ALT) ≤ 3.0 times upper limit of normal
- Upper limit of normal is defined by the clinical laboratory performing the test.
- Creatinine clearance is obtained using the lean body mass formula (Modified Cockcroft Gault)
- If transaminase elevation and/or bilirubin elevation is attributed to the presence of liver metastases, a total bilirubin ≤ 2.5 times the upper limit of normal and an Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 2.5 times the upper limit of normal are permissible. Patients with an elevated bilirubin level that is attributed to an inherited disorder, such as Gilbert's disease, may be enrolled at the discretion of the principal investigator.
- Patients may not receive platelet transfusions within 3 weeks of initiating protocol therapy.
- Meet the following criteria regarding contraception:
- Female patients who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
- Male patients who: (must meet criteria even if surgically sterilized, i.e. after vasectomy):
- Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
Who cannot join
- Received selinexor or another XPO1 inhibitor previously.
- Received ixazomib or another proteasome inhibitor previously.
- Currently pregnant or lactating.
- Prior malignancy that required treatment, or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to registration. Cancer treated with curative intent more than 5 years previously and without evidence of recurrence is not an exclusion.
- Received any systemic anticancer therapy including investigational agents or radiation ≤3 weeks (or ≤5 half-lives of the drug, whichever is longer) prior to registration. Patients must have recovered to grade ≤ 1 or baseline from clinically significant adverse effects associated with prior anti-cancer therapies except for alopecia or controlled endocrinopathies.
- Major surgery within 2 weeks of first dose of study treatment.
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- Any serious medical or psychiatric illness, medical condition or organ dysfunction which, in the investigator's opinion, could compromise patient safety or compliance with the protocol.
- Unstable cardiovascular function as defined by:
- Symptomatic ischemia, or
- Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree arterioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or
- Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥3, or
- Myocardial infarction (MI) within 6 months
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment. Prophylactic use of antibiotics and/or antivirals is acceptable.
- Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positivity.
- History of clinically significant ocular disease manifest by visual defects or disturbances, including those caused by active glaucoma or cataracts, which have not been addressed by surgery or other corrective intervention. If necessary, an opthalmologic exam should be performed at screening.
- Inability to swallow tablets, clinically significant malabsorption syndrome, or any other GI disease or dysfunction that could interfere with absorption of study drugs.
- Presence of grade 3 peripheral neuropathy or grade 2 peripheral neuropathy with pain at any time during the screening period.
- Systemic treatment, within 14 days before initiation of study treatment, with strong CYP3A4 inducers (including, but not limited to rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort.
- Unwillingness to comply with the study protocol and/or procedures.
- Central nervous system involvement.
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: A Phase I Study of the Selective Inhibitor of Nuclear Export (SINE) Selinexor in Combination With the Proteasome Inhibitor Ixazomib for the Treatment of Advanced Sarcoma
The main purpose of this study is to establish a safe and tolerable dose combination (the "maximum tolerated dose") of selinexor and ixazomib when used together for the treatment of patients with certain types of advanced sarcoma. The study will enroll patients with advanced dedifferentiated liposarcoma, malignant peripheral nerve sheath tumor, alveolar soft part sarcoma and Ewing sarcoma. Future studies to further evaluate the safety and anti-cancer efficacy of this treatment for sarcoma will use the dose combination determined in this study.
Read the detailed description
Sarcoma is a rare form of cancer which originates from the soft tissues and bones of the body. There are more than 50 different types of sarcoma. The primary treatment approach for most types of advanced sarcoma involves chemotherapy, but newer treatment approaches are needed because chemotherapy is not curative, sometimes does not work well, and often has significant side effects.
The purpose of this study is to evaluate a new treatment for certain types of sarcoma. The new treatment involves two oral targeted drugs used in combination: selinexor and ixazomib. Selinexor inhibits the transport of certain proteins between the nucleus and the cytoplasm of the cell. Ixazomib is part of a class of drugs called proteasome inhibitors. Currently, neither of these drugs is approved for the treatment of sarcoma. The researchers believe this combination treatment may work effectively for certain types of sarcoma based on encouraging laboratory research results. The types of sarcoma in which the treatment will be tested are: dedifferentiated liposarcoma, alveolar soft part sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma. The purpose of this study is to define doses of selinexor and ixazomib that are safe and tolerable for patients.
- Conditions
- Liposarcoma, Malignant Peripheral Nerve Sheath Tumors, Alveolar Soft Part Sarcoma, Ewing Sarcoma, Sarcoma
- Being tested
- Selinexor, Ixazomib
- Keywords
- Liposarcoma, Malignant Peripheral Nerve Sheath Tumors, Alveolar Soft Part Sarcoma, Ewing Sarcoma, Selinexor, ixazomib, sarcoma, kpt-330
- Medical subject headings
- Liposarcoma, Neurofibrosarcoma, Sarcoma, Alveolar Soft Part, Sarcoma, Ewing, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelinexorDrug
Also called KPT-330
Selinexor will be taken orally on Days 1, 8, 15, and 22 of each cycle at the following dose levels (DLs):
DL 1: 40 mg; DL 2: 60 mg; DL 3: 80 mg; DL 4: 100 mg
The selinexor product is provided as 20 mg tablets in wallet-sized blister packs. Selinexor should be taken together with ixazomib.
IxazomibDrug
Also called Ninlaro
Ixazomib will be taken orally on Days 1, 8, and 15 of each cycle at the same dose level: 4 mg.
The ixazomib product is provided in strengths of 4.0, 3.0, and 2.3 mg capsules as the active boronic acid. Ixazomib should be taken on an empty stomach (no food or drink) at least 1 hour before or at least 2 hours after food.
| Study group | Role | What they receive |
|---|---|---|
| Selinexor/Ixazomib | Experimental | Patients will receive combination treatment with selinexor and ixazomib. The dose of ixazomib is fixed at 4 mg, whereas several different dose levels of selinexor may be evaluated. No patients will receive a placebo. Receives: Drug: Selinexor; Drug: Ixazomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
To establish the maximum tolerated dose combination for selinexor and ixazomib when used as a combination treatment for patients with dedifferentiated liposarcoma, malignant peripheral nerve sheath tumor, alveolar soft part sarcoma and Ewing sarcoma. The MTD is defined by the time to event continual reassessment method, a model-based dose finding study design.
Measured: Up to 2 years
Secondary outcomes (1)
Adverse Event (AE) Rate
Adverse events will be collected from the day the patient receives the first dose of study treatment until 30 days after end-of-treatment. Adverse events will be reported by Common Terminology Criteria for Adverse Events (CTCAE criteria), stratified by grade.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2019
- Study startNov 2020 (estimated)
- Primary completion24 Nov 2020
- Study completion24 Nov 2020
Why it stopped: Study will not proceed, no participants enrolled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LiposarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Matthew Ingham
- Sponsor type
- University, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc, Takeda
- Responsible party
- Sponsor-investigator, Matthew Ingham, Columbia University
- Investigators
- Matthew Ingham, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03880123
- Sponsor's protocol ID
- AAAS0199
- Status last verified
- Nov 2020
- First submitted
- 15 Mar 2019
- Last updated
- 27 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the Selective Inhibitor of Nuclear Export (SINE) Selinexor in Combination With the Proteasome Inhibitor Ixazomib for the Treatment of Advanced Sarcoma
- ClinicalTrials.gov ID
- NCT03880123
- Acronym / sponsor ID
- AAAS0199
- Conditions
- Liposarcoma, Malignant Peripheral Nerve Sheath Tumors, Alveolar Soft Part Sarcoma, Ewing Sarcoma, Sarcoma
- Keywords
- Liposarcoma, Malignant Peripheral Nerve Sheath Tumors, Alveolar Soft Part Sarcoma, Ewing Sarcoma, Selinexor, ixazomib, sarcoma, kpt-330
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study will not proceed, no participants enrolled.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Matthew InghamUniversity, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc, Takeda
- Study start
- Nov 2020 (estimated)
- Primary completion
- 24 Nov 2020 (actual)
- Study completion
- 24 Nov 2020 (actual)
- First posted
- 19 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to establish a safe and tolerable dose combination (the "maximum tolerated dose") of selinexor and ixazomib when used together for the treatment of patients with certain types of advanced sarcoma. The study will enroll patients with advanced dedifferentiated liposarcoma, malignant peripheral nerve sheath tumor, alveolar soft part sarcoma and Ewing sarcoma. Future studies to further evaluate the safety and anti-cancer efficacy of this treatment for sarcoma will use the dose combination determined in this study.
Detailed description
Sarcoma is a rare form of cancer which originates from the soft tissues and bones of the body. There are more than 50 different types of sarcoma. The primary treatment approach for most types of advanced sarcoma involves chemotherapy, but newer treatment approaches are needed because chemotherapy is not curative, sometimes does not work well, and often has significant side effects.
The purpose of this study is to evaluate a new treatment for certain types of sarcoma. The new treatment involves two oral targeted drugs used in combination: selinexor and ixazomib. Selinexor inhibits the transport of certain proteins between the nucleus and the cytoplasm of the cell. Ixazomib is part of a class of drugs called proteasome inhibitors. Currently, neither of these drugs is approved for the treatment of sarcoma. The researchers believe this combination treatment may work effectively for certain types of sarcoma based on encouraging laboratory research results. The types of sarcoma in which the treatment will be tested are: dedifferentiated liposarcoma, alveolar soft part sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma. The purpose of this study is to define doses of selinexor and ixazomib that are safe and tolerable for patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Selinexor/Ixazomib | Experimental | Drug: Selinexor, Drug: IxazomibPatients will receive combination treatment with selinexor and ixazomib. The dose of ixazomib is fixed at 4 mg, whereas several different dose levels of selinexor may be evaluated. No patients will receive a placebo. |
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (23 listed)
- Signed written informed consent.
- Age ≥ 14 years
- Body surface area ≥ 1.2 m2
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Histologically confirmed de-differentiated liposarcoma, malignant peripheral nerve sheath tumor, alveolar soft part sarcoma or Ewing sarcoma. Liposarcomas with areas of well-differentiated disease are eligible if there is a biopsy-proven component of dedifferentiated liposarcoma. Pathology is reviewed at Columbia University Medical Center.
Key exclusion criteria (22 listed)
- Received selinexor or another XPO1 inhibitor previously.
- Received ixazomib or another proteasome inhibitor previously.
- Currently pregnant or lactating.
- Prior malignancy that required treatment, or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to registration. Cancer treated with curative intent more than 5 years previously and without evidence of recurrence is not an exclusion.
- Received any systemic anticancer therapy including investigational agents or radiation ≤3 weeks (or ≤5 half-lives of the drug, whichever is longer) prior to registration. Patients must have recovered to grade ≤ 1 or baseline from clinically significant adverse effects associated with prior anti-cancer therapies except for alopecia or controlled endocrinopathies.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelinexorAlso: KPT-330Selinexor will be taken orally on Days 1, 8, 15, and 22 of each cycle at the following dose levels (DLs): DL 1: 40 mg; DL 2: 60 mg; DL 3: 80 mg; DL 4: 100 mg The selinexor product is provided as 20 mg tablets in wallet-sized blister packs. Selinexor should be taken together with ixazomib. | Drug | Selinexor/Ixazomib |
| IxazomibAlso: NinlaroIxazomib will be taken orally on Days 1, 8, and 15 of each cycle at the same dose level: 4 mg. The ixazomib product is provided in strengths of 4.0, 3.0, and 2.3 mg capsules as the active boronic acid. Ixazomib should be taken on an empty stomach (no food or drink) at least 1 hour before or at least 2 hours after food. | Drug | Selinexor/Ixazomib |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Up to 2 years
To establish the maximum tolerated dose combination for selinexor and ixazomib when used as a combination treatment for patients with dedifferentiated liposarcoma, malignant peripheral nerve sheath tumor, alveolar soft part sarcoma and Ewing sarcoma. The MTD is defined by the time to event continual reassessment method, a model-based dose finding study design.
1 secondary outcome
Adverse Event (AE) Rate
Time frame: Up to 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Ingham, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Selinexor and Ixazomib in people with Liposarcoma and Malignant Peripheral Nerve Sheath Tumors, run by Matthew Ingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 27 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2020.