Trial of Sunitinib in Patients With Type B3 Thymoma or Thymic Carcinoma in Second and Further Lines (Style Trial)

NCT03449173 | Unknown Phase 2

• 1 other identifier: INT 165-16
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type B3 Thymoma; Thymic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Activity of Sunitinib

  Best tumour response (Complete Response + Partial Response)

  4 years

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  4 years

• Overall Survival (OS)

  4 years

• Duration of activity of sunitinib

  4 years

• Safety and toxicity profile of sunitinib

  4 years

• Incidence of adverse events (AEs)

  4 years

Study Arms (1)

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

Drug: Sunitinib

Interventions

Sunitinib DRUG

small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor

Also known as: Sutent

Sunitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

National Cancer Institute

Milan, 20133, Italy

RECRUITING

Related Publications (9)

• 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

  BACKGROUND

• 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.

  PMID: 25592632 BACKGROUND

• Salter JT et al. Imatinib for the treatment of thymic carcinoma. JCO 26: ASCO 2008 (May 20 Supplement): Abs.

  BACKGROUND

• 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.

  PMID: 12712448 RESULT

• Wright 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.

  PMID: 17570676 RESULT

• Giaccone G. Treatment of malignant thymoma. Curr Opin Oncol. 2005 Mar;17(2):140-6. doi: 10.1097/01.cco.0000152628.43867.8e.

  PMID: 15725919 RESULT

• Serpico 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.

  PMID: 25411417 RESULT

• Strobel 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.

  PMID: 15201427 RESULT

• Bisagni 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.

  PMID: 19461405 RESULT

MeSH Terms

Conditions

Thymoma

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Thymus Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Marina Chiara Garassino, MD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marina Chiara Garassino, MD

CONTACT

+390223903813; marina.garassino@istitutotumori.mi.it

Rosaria Gallucci, MSc

CONTACT

+390223903836; rosaria.gallucci@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2018
• First Posted: February 28, 2018
• Study Start: March 2, 2017
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: June 9, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)