A Study of Drug Therapies for Salivary Gland Cancers Based on Testing of Genes

Sponsor

University Health Network, Toronto (Other)

Overall Status

Recruiting

CT.gov ID

NCT02069730

Collaborator

(none)

200

Enrollment

Location

Arms

162

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a study of select drug therapies in patients with salivary gland cancer. The study has two phases: a molecular profiling phase (phase 1) and a treatment phase (phase 2).

Based on the Molecular profiling results in phase the participants will receive matched treatment if a specific aberration is identified or will receive treatment with Selinexor if unmatched and no druggable aberration is identified.

Condition or Disease	Intervention/Treatment	Phase
Salivary Gland Cancer Metastatic Advanced Recurrent	Drug: Selinexor Drug: EGFR or HER2 Inhibitor Drug: FGFR Inhibitor Drug: C-KIT Inhibitor Drug: Anti-androgen Drug: NOTCH Inhibitor Drug: MEK or PI3K Inhibitor	N/A

Detailed Description

In molecular profiling phase of the study, participants will provide a sample of their tumor tissue to test for changes in certain genes that show whether certain drug treatments will be more useful than others.

Once participants have undergone molecular profiling, they will be offered a drug treatment depending on the results. Certain drug treatments are designed to target certain gene changes. If there is a matching drug treatment, participants will be offered that treatment (either outside a clinical trial or within a clinical trial). If there are no gene changes or there are changes to genes were there are no drug treatments available for those certain changes, participants will be offered the study drug, Selinexor.

Cancer is the uncontrolled growth of cells. Research shows that one way cancer cells can grow uncontrollably is when certain proteins, called exporter proteins, are present in high levels in the body. These proteins prevent certain other proteins important in protecting cells from becoming cancerous and important in the controlling the growth of cells, from working. The study drug Selinexor is new class of drug called Selective Inhibitor of Nuclear Export (SINE) that blocks the exporter proteins from working which may allow the other proteins to work and slow or stop tumors from growing.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Genomic Profiling and Matched Therapy for Recurrent or Metastatic Salivary Gland Neoplasms

Study Start Date :

Jun 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Unmatched Treatment (Selinexor) Selinexor, 30mg/m2, by mouth, twice weekly, every 28 day cycles. If patients have a "druggable" aberration but there is no access to the relevant agent, then patients will receive selinexor	Drug: Selinexor If no "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive unmatched treatment with Selinexor, a selective inhibitor of nuclear export (SINE). Other Names: KPT-330
Experimental: Matched Therapy EGFR or HER2 Inhibitor,FGFR Inhibitor,C-KIT Inhibitor, Anti-androgen ,NOTCH Inhibitor,MEK or PI3K Inhibitor . If the matched therapy is given through a clinical trial, the dosing schedule will be determined by that particular trial protocol. For matched treatments administered outside of a clinical trial, the dosing schedule will be the recommended dose by the expertise of the treating investigator.	Drug: EGFR or HER2 Inhibitor If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with EGFR or HER2 Inhibitor Other Names: Matched treatment Drug: FGFR Inhibitor If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with FGFR Inhibitor Other Names: Matched treatment Drug: C-KIT Inhibitor If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with C-KIT Inhibitor Other Names: Matched Treatment Drug: Anti-androgen If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with Anti-androgens Other Names: Matched Treatment Drug: NOTCH Inhibitor If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with NOTCH Inhibitor Other Names: Matched Treatment Drug: MEK or PI3K Inhibitor If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with MEK or PI3K Inhibitor Other Names: Matched Treatment

Arm

Intervention/Treatment

Experimental: Unmatched Treatment (Selinexor)

Selinexor, 30mg/m2, by mouth, twice weekly, every 28 day cycles. If patients have a "druggable" aberration but there is no access to the relevant agent, then patients will receive selinexor

Drug: Selinexor

If no "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive unmatched treatment with Selinexor, a selective inhibitor of nuclear export (SINE).

Other Names:

KPT-330

Experimental: Matched Therapy

EGFR or HER2 Inhibitor,FGFR Inhibitor,C-KIT Inhibitor, Anti-androgen ,NOTCH Inhibitor,MEK or PI3K Inhibitor . If the matched therapy is given through a clinical trial, the dosing schedule will be determined by that particular trial protocol. For matched treatments administered outside of a clinical trial, the dosing schedule will be the recommended dose by the expertise of the treating investigator.

Drug: EGFR or HER2 Inhibitor

If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with EGFR or HER2 Inhibitor

Other Names:

Matched treatment

Drug: FGFR Inhibitor

If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with FGFR Inhibitor

Other Names:

Matched treatment

Drug: C-KIT Inhibitor

If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with C-KIT Inhibitor

Other Names:

Matched Treatment

Drug: Anti-androgen

If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with Anti-androgens

Other Names:

Matched Treatment

Drug: NOTCH Inhibitor

If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with NOTCH Inhibitor

Other Names:

Matched Treatment

Drug: MEK or PI3K Inhibitor

If specific "druggable" aberrations are identified on the molecular profiling analysis, then patients will receive matched treatment with MEK or PI3K Inhibitor

Other Names:

Matched Treatment

Outcome Measures

Primary Outcome Measures

Number of participants with complete and partial response to unmatched therapy Selinexor compared to matched therapies [4 years]
Overall Response rate in the setting of matched and unmatched therapy.

Secondary Outcome Measures

Number of participants with complete, partial and/or stable disease to unmatched therapy Selinexor compared to matched therapies [4 years]
Disease control Rate in the setting of matched and unmatched therapy.
Length of time that participant's disease does not worsen [6 months]
Progression free survival rate in the setting of matched and unmatched therapy.
Percentage of each molecular aberrations in metastatic salivary gland tumors [4 years]
Molecular profiling results in malignant salivary gland tumor

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria (Phase 1, Molecular Profiling):

Have available archival tumor tissue or fresh tumor specimen from diagnostic histological tissue for molecular profiling.
Histological or cytological proof of malignant salivary gland tumor
ECOG performance score 0-2
Documented evidence of recurrent or metastatic disease

Inclusion Criteria (Phase 2, Treatment):

Interpretable result of molecular profiling in the molecular profiling phase of this study
Advanced recurrent or metastatic salivary gland cancer for which no curative therapy exists
Evidence of clinical or radiological disease progression at the time of study treatment
At least one measurable target lesion as defined by RECIST 1.1
Must have adequate hematological, liver, renal and cardiac function
No concomitant use of drugs which may prolong QTc interval
No history of serious cardiac illness
No serious medical conditions that might be aggravated by treatment or limit compliance.
Central nervous system metastases are permitted provided these are clinically stable
Able to take oral medication and have no evidence of bowel obstruction, infectious/inflammatory bowel disease
No other active malignancy at any other site
18 years of age or older
Measureable disease as defined by RECIST v1.1
Not receiving any other concurrent investigational agent
If the matched treatment is in the context of another phase I trial, the eligibility criteria of the enrolled trial will be used instead of the criteria from this trial

Exclusion Criteria (Phase 1, Molecular Profiling):

Refuses to have tumor tissue undergo molecular profiling
Not enough tumor tissue for molecular profiling
Life expectancy less than 3 months

Exclusion Criteria (Phase 2, Treatment):

Had stopped the previous treatment but showed no clinical or radiological evidence of disease progression
Have received the same drug treatment of assignment to the specific arm before the enrolment in to treatment phase (phase 2)