Type B3 ThymomaPhase 2StyleNCT03449173
Trial of Sunitinib in Patients With Type B3 Thymoma or Thymic Carcinoma in Second and Further Lines (Style Trial)
A Phase 2 study testing Sunitinib in people with Type B3 Thymoma and Thymic Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
Study to investigate response to sunitinib in patients with thymic epithelial tumours who had progressive disease after at least one previous regimen of platinum-based chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type B3 Thymoma, Thymic Carcinoma
- What is being tested?
- Sunitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteItaly
- Study dates
- 2 Mar 2017to 31 May 2022
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed and dated IRB (Independent Review Board)/IEC (Independent Ethics Committee)-approved Informed Consent
- Histological diagnosis of invasive recurrent or metastatic type B3 thymoma or thymic carcinoma. In case of presence of both histologies it will be classified based on the predominantly part. B2 thymoma with areas of B3 thymoma are eligible.
- Patients must have had at least one prior platinum-containing chemotherapy regimen. There is no limit to the number of prior chemotherapy regimens or targeted agents received. Progressive disease should have been documented before entry into the study
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured according with RECIST 1.1 criteria
- Availability of archival tissue (paraffine block or at least 10 unstained slides)
- Patients must have recovered from toxicity related to prior therapy to at least grade 1 (defined by v.CTCAE 4.0)
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- Patients must not have had major surgery, radiation therapy, chemotherapy, biologic therapy (including any investigational agents), or hormonal therapy (other than replacement), within 4 weeks prior to entering the study
- Age > 18 years
- Life expectancy > 3 months
- Performance status (ECOG) ≤ 2
- Negative pregnancy test (if female in reproductive years)
- Patients must have adequate organ and marrow function (as defined below). Patients must have returned to baseline or grade 1 from any acute toxicity related to prior therapy:
- Absolute neutrophil count ≥ 1,500/mm
- Hemoglobin ≥ 9 g/dL
- Platelets ≥ 100,000/mm
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) , except for patients affected by Gilbert's syndrome
- AST(SGOT) (aspartate aminotransferase) /ALT(SGPT) (alanine transaminase) ≤ 3 x institutional ULN (5x if LFT (liver function test) elevations due to liver metastases)
- Creatinine ≤ 1.5 x institutional ULN
- Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception before study entry, for all the duration of the study and for at least 8 weeks after the last dose of investigational drug (30 days for an ovarian cycle turnover plus the time required for the active metabolite of sunitinib to undergo five half-lives).
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of before study entry, for all the duration of the study and for at least 16 weeks after the last dose of investigational drug (90 days for sperm turnover plus the time required for the active metabolite of sunitinib to undergo five half-lives).
Who cannot join
- untreated CNS metastases. Patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) ending at least 2 weeks prior to start of treatment, or after surgical resection performed at least 28 days prior to start of treatment. The patient may have no evidence of Grade ≥1 CNS haemorrhage based on pre-treatment Magnetic Resonance Imaging (MRI) or IV contrast CT scan (performed within 28 days before start of treatment)
- Major surgery, other than diagnostic surgery, within 4 weeks prior to treatment
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Pregnant or breast feeding women
- Previous (within the last 5 years) or current malignancies at other sites, except for adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri
- Current enrollment in or participation in another therapeutic clinical trial within 4 weeks before treatment start.
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- Patients with uncontrolled or significant cardiovascular disease (AMI within 12 months, unstable angina within 6 months, NYHA (New York Heart Association) Class III, IV Congestive heart failure or left ventricular ejection fraction below local institutional lower limit of normal or below 45%,
- Ongoing symptomatic cardiac dysrhythmias, uncontrolled atrial fibrillation, or prolongation of the Fridericia corrected QT (QTcF) interval defined as > 450 msec for males and > 470 msec for females, where QTcF = QT / 3√RR
- Poorly controlled hypertension
- History of cerebrovascular accident including transient ischemic attack within the past 12 months.
- History of deep vein thrombosis (DVT) unless adequately treated with low molecular weight heparin
- History of pulmonary embolism within the past 6 months unless stable, asymptomatic, and treated with low molecular weight heparin for at least 6 weeks.
- Evidence of active bleeding or bleeding susceptibility; or medically significant hemorrhage within prior 30 days.
- Receiving concomitant CYP3A4 inducers or strong CYP3A4 inhibitors
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of sunitinib
- Known HIV infection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial of Sunitinib in Patients With Type B3 Thymoma or Thymic Carcinoma in Second and Further Lines (Style Trial)
Study to investigate response to sunitinib in patients with thymic epithelial tumours who had progressive disease after at least one previous regimen of platinum-based chemotherapy.
Read the detailed description
This trial will be conducted to assess the activity of Sunitinib in patients affected by advanced or recurrent B3 thymoma or thymic carcinoma progressing after at least one line of chemotherapy (including one platinum based regimen).
Taking into account the different biology and historically discrepant responses and survival of thymoma and thymic carcinoma, patients will be enrolled with these tumour types in two separate cohorts.
Sunitinib will be self orally administered at 50 mg once daily, is 50 mg taken orally once daily, for 4 consecutive weeks, followed by a 2-week rest period (schedule 4/2) to comprise a complete cycle of 6 weeks until tumour progression, unacceptable toxicity or other criteria for discontinuation is met.
Sunitinib dose reductions are permitted as per the approved product label for safety reasons.
Dose reductions should occur in 12.5 mg decrements. No more than 2 dose reductions are allowed. If more than 2 dose reductions are necessary (ie, reduction to less than 25 mg daily), the subject must be permanently discontinued (Section 7.2.2)
Possible dose reductions:
- Sunitinib at dose of 37,5 mg orally once daily for 4 weeks followed by 2 weeks rest-period in cycles of 6 weeks.
- Sunitinib at dose of 25 mg orally once daily for 4 weeks followed by 2 weeks rest-period in cycles of 6 weeks
- Conditions
- Type B3 Thymoma, Thymic Carcinoma
- Being tested
- Sunitinib
- Medical subject headings
- Thymoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Also called Sutent
small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib | Experimental | Sunitinib orally administered at 50 mg once daily for 4 consecutive weeks, followed by a 2-week rest period (schedule 4/2) to comprise a complete cycle of 6 weeks Receives: Drug: Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Activity of Sunitinib
Best tumour response (Complete Response + Partial Response)
Measured: 4 years
Secondary outcomes (5)
Progression Free Survival (PFS)
The PFS is defined as the time from the date of randomization to the date of documented progressive disease, recurrence or Death (whichever occurs first)
Measured: 4 years
Overall Survival (OS)
The OS is defined as the time from the date of randomization to the date of death
Measured: 4 years
Duration of activity of sunitinib
Complete Response + Partial Response + Stable Disease
Measured: 4 years
Safety and toxicity profile of sunitinib
will be utilized the CTCAE v 4.0 criteria for assessment of toxicity and serious adverse event reporting.
Measured: 4 years
Incidence of adverse events (AEs)
Incidence of adverse events (AEs) will be graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0, laboratory values, physical examinations, vital signs.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2018
- Study start2 Mar 2017
- Primary completion31 May 2022 (estimated)
- Study completion31 May 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Type B3 ThymomaStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marina Chiara Garassino, MD, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03449173
- Sponsor's protocol ID
- INT 165-16
- Acronym
- Style
- Status last verified
- Jun 2021
- First submitted
- 22 Feb 2018
- Last updated
- 9 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kurup A et al. Phase II study of gefitinib treatment in advanced thymic malignancies. JCO 23 (16S, Part I of II, June 1 Supplement), ASCO 2005: Abs. 7068
Thomas A, Rajan A, Berman A, Tomita Y, Brzezniak C, Lee MJ, Lee S, Ling A, Spittler AJ, Carter CA, Guha U, Wang Y, Szabo E, Meltzer P, Steinberg SM, Trepel JB, Loehrer PJ, Giaccone G. Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol. 2015 Feb;16(2):177-86. doi: 10.1016/S1470-2045(14)71181-7. Epub 2015 Jan 13.
PubMed 25592632Salter JT et al. Imatinib for the treatment of thymic carcinoma. JCO 26: ASCO 2008 (May 20 Supplement): Abs.
Engels EA, Pfeiffer RM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer. 2003 Jul 1;105(4):546-51. doi: 10.1002/ijc.11099.
PubMed 12712448Wright CD. Management of thymomas. Crit Rev Oncol Hematol. 2008 Feb;65(2):109-20. doi: 10.1016/j.critrevonc.2007.04.005. Epub 2007 Jun 14.
PubMed 17570676Giaccone G. Treatment of malignant thymoma. Curr Opin Oncol. 2005 Mar;17(2):140-6. doi: 10.1097/01.cco.0000152628.43867.8e.
PubMed 15725919Serpico D, Trama A, Haspinger ER, Agustoni F, Botta L, Berardi R, Palmieri G, Zucali P, Gallucci R, Broggini M, Gatta G, Pastorino U, Pelosi G, de Braud F, Garassino MC. Available evidence and new biological perspectives on medical treatment of advanced thymic epithelial tumors. Ann Oncol. 2015 May;26(5):838-847. doi: 10.1093/annonc/mdu527. Epub 2014 Nov 19.
PubMed 25411417Strobel P, Hartmann M, Jakob A, Mikesch K, Brink I, Dirnhofer S, Marx A. Thymic carcinoma with overexpression of mutated KIT and the response to imatinib. N Engl J Med. 2004 Jun 17;350(25):2625-6. doi: 10.1056/NEJM200406173502523. No abstract available.
PubMed 15201427Bisagni G, Rossi G, Cavazza A, Sartori G, Gardini G, Boni C. Long lasting response to the multikinase inhibitor bay 43-9006 (Sorafenib) in a heavily pretreated metastatic thymic carcinoma. J Thorac Oncol. 2009 Jun;4(6):773-5. doi: 10.1097/JTO.0b013e3181a52e25.
PubMed 19461405
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Sunitinib in Patients With Type B3 Thymoma or Thymic Carcinoma in Second and Further Lines (Style Trial)
- ClinicalTrials.gov ID
- NCT03449173
- Acronym / sponsor ID
- Style / INT 165-16
- Conditions
- Type B3 Thymoma, Thymic Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- 2 Mar 2017 (actual)
- Primary completion
- 31 May 2022 (estimated)
- Study completion
- 31 May 2022 (estimated)
- First posted
- 28 Feb 2018 (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.
Study to investigate response to sunitinib in patients with thymic epithelial tumours who had progressive disease after at least one previous regimen of platinum-based chemotherapy.
Detailed description
This trial will be conducted to assess the activity of Sunitinib in patients affected by advanced or recurrent B3 thymoma or thymic carcinoma progressing after at least one line of chemotherapy (including one platinum based regimen).
Taking into account the different biology and historically discrepant responses and survival of thymoma and thymic carcinoma, patients will be enrolled with these tumour types in two separate cohorts.
Sunitinib will be self orally administered at 50 mg once daily, is 50 mg taken orally once daily, for 4 consecutive weeks, followed by a 2-week rest period (schedule 4/2) to comprise a complete cycle of 6 weeks until tumour progression, unacceptable toxicity or other criteria for discontinuation is met.
Sunitinib dose reductions are permitted as per the approved product label for safety reasons.
Dose reductions should occur in 12.5 mg decrements. No more than 2 dose reductions are allowed. If more than 2 dose reductions are necessary (ie, reduction to less than 25 mg daily), the subject must be permanently discontinued (Section 7.2.2)
Possible dose reductions:
- Sunitinib at dose of 37,5 mg orally once daily for 4 weeks followed by 2 weeks rest-period in cycles of 6 weeks.
- Sunitinib at dose of 25 mg orally once daily for 4 weeks followed by 2 weeks rest-period in cycles of 6 weeks
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib | Experimental | Drug: SunitinibSunitinib orally administered at 50 mg once daily for 4 consecutive weeks, followed by a 2-week rest period (schedule 4/2) to comprise a complete cycle of 6 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Signed and dated IRB (Independent Review Board)/IEC (Independent Ethics Committee)-approved Informed Consent
- Histological diagnosis of invasive recurrent or metastatic type B3 thymoma or thymic carcinoma. In case of presence of both histologies it will be classified based on the predominantly part. B2 thymoma with areas of B3 thymoma are eligible.
- Patients must have had at least one prior platinum-containing chemotherapy regimen. There is no limit to the number of prior chemotherapy regimens or targeted agents received. Progressive disease should have been documented before entry into the study
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured according with RECIST 1.1 criteria
- Availability of archival tissue (paraffine block or at least 10 unstained slides)
Key exclusion criteria (16 listed)
- untreated CNS metastases. Patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) ending at least 2 weeks prior to start of treatment, or after surgical resection performed at least 28 days prior to start of treatment. The patient may have no evidence of Grade ≥1 CNS haemorrhage based on pre-treatment Magnetic Resonance Imaging (MRI) or IV contrast CT scan (performed within 28 days before start of treatment)
- Major surgery, other than diagnostic surgery, within 4 weeks prior to treatment
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Pregnant or breast feeding women
- Previous (within the last 5 years) or current malignancies at other sites, except for adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri
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 |
|---|---|---|
| SunitinibAlso: Sutentsmall-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor | Drug | Sunitinib |
Primary outcome
Activity of Sunitinib
Time frame: 4 years
Best tumour response (Complete Response + Partial Response)
5 secondary outcomes
Progression Free Survival (PFS)
Time frame: 4 years
Overall Survival (OS)
Time frame: 4 years
Duration of activity of sunitinib
Time frame: 4 years
Safety and toxicity profile of sunitinib
Time frame: 4 years
Incidence of adverse events (AEs)
Time frame: 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2021.
- BackgroundKurup A et al. Phase II study of gefitinib treatment in advanced thymic malignancies. JCO 23 (16S, Part I of II, June 1 Supplement), ASCO 2005: Abs. 7068
- Background: PubMed 25592632Thomas A, Rajan A, Berman A, Tomita Y, Brzezniak C, Lee MJ, Lee S, Ling A, Spittler AJ, Carter CA, Guha U, Wang Y, Szabo E, Meltzer P, Steinberg SM, Trepel JB, Loehrer PJ, Giaccone G. Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol. 2015 Feb;16(2):177-86. doi: 10.1016/S1470-2045(14)71181-7. Epub 2015 Jan 13.
- BackgroundSalter JT et al. Imatinib for the treatment of thymic carcinoma. JCO 26: ASCO 2008 (May 20 Supplement): Abs.
- Results publication: PubMed 12712448Engels EA, Pfeiffer RM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer. 2003 Jul 1;105(4):546-51. doi: 10.1002/ijc.11099.
- Results publication: PubMed 17570676Wright CD. Management of thymomas. Crit Rev Oncol Hematol. 2008 Feb;65(2):109-20. doi: 10.1016/j.critrevonc.2007.04.005. Epub 2007 Jun 14.
- Results publication: PubMed 15725919Giaccone G. Treatment of malignant thymoma. Curr Opin Oncol. 2005 Mar;17(2):140-6. doi: 10.1097/01.cco.0000152628.43867.8e.
- Results publication: PubMed 25411417Serpico D, Trama A, Haspinger ER, Agustoni F, Botta L, Berardi R, Palmieri G, Zucali P, Gallucci R, Broggini M, Gatta G, Pastorino U, Pelosi G, de Braud F, Garassino MC. Available evidence and new biological perspectives on medical treatment of advanced thymic epithelial tumors. Ann Oncol. 2015 May;26(5):838-847. doi: 10.1093/annonc/mdu527. Epub 2014 Nov 19.
- Results publication: PubMed 15201427Strobel P, Hartmann M, Jakob A, Mikesch K, Brink I, Dirnhofer S, Marx A. Thymic carcinoma with overexpression of mutated KIT and the response to imatinib. N Engl J Med. 2004 Jun 17;350(25):2625-6. doi: 10.1056/NEJM200406173502523. No abstract available.
- Results publication: PubMed 19461405Bisagni G, Rossi G, Cavazza A, Sartori G, Gardini G, Boni C. Long lasting response to the multikinase inhibitor bay 43-9006 (Sorafenib) in a heavily pretreated metastatic thymic carcinoma. J Thorac Oncol. 2009 Jun;4(6):773-5. doi: 10.1097/JTO.0b013e3181a52e25.
- Individual participant dataSharing planned: No
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Active, not recruitingPhase 2
Nivolumab in Patients With Type B3 Thymoma and Thymic Carcinoma (NIVOTHYM)
Thymoma Type B3, Thymic Carcinoma
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.
Marina Chiara Garassino, MD principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sunitinib in people with Type B3 Thymoma and Thymic Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
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 20 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 9 Jun 2021. 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 Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marina Chiara Garassino, MD (+390223903813, marina.garassino@istitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Activity of Sunitinib (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03449173, which also lists 9 linked publications.
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 9 Jun 2021.