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

Last updated: June 8, 2021
Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Overall Status: Active - Recruiting

Phase

2

Condition

Head And Neck Cancer

Carcinoma

Thymomas

Treatment

N/A

Clinical Study ID

NCT03449173
INT 165-16
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Signed and dated IRB (Independent Review Board)/IEC (Independent EthicsCommittee)-approved Informed Consent
  2. Histological diagnosis of invasive recurrent or metastatic type B3 thymoma or thymiccarcinoma. In case of presence of both histologies it will be classified based on thepredominantly part. B2 thymoma with areas of B3 thymoma are eligible.
  3. 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 agentsreceived. Progressive disease should have been documented before entry into the study
  4. Patients must have measurable disease, defined as at least one lesion that can beaccurately measured according with RECIST 1.1 criteria
  5. Availability of archival tissue (paraffine block or at least 10 unstained slides)
  6. Patients must have recovered from toxicity related to prior therapy to at least grade 1 (defined by v.CTCAE 4.0)
  7. Patients must not have had major surgery, radiation therapy, chemotherapy, biologictherapy (including any investigational agents), or hormonal therapy (other thanreplacement), within 4 weeks prior to entering the study
  8. Age > 18 years
  9. Life expectancy > 3 months
  10. Performance status (ECOG) ≤ 2
  11. Negative pregnancy test (if female in reproductive years)
  12. Patients must have adequate organ and marrow function (as defined below). Patientsmust have returned to baseline or grade 1 from any acute toxicity related to priortherapy:
  • 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 forpatients affected by Gilbert's syndrome
  • AST(SGOT) (aspartate aminotransferase) /ALT(SGPT) (alanine transaminase) ≤ 3 xinstitutional ULN (5x if LFT (liver function test) elevations due to livermetastases)
  • Creatinine ≤ 1.5 x institutional ULN
  1. Women of childbearing potential (WOCBP) must agree to follow instructions formethod(s) of contraception before study entry, for all the duration of the study andfor at least 8 weeks after the last dose of investigational drug (30 days for anovarian cycle turnover plus the time required for the active metabolite of sunitinibto undergo five half-lives).
  2. Males who are sexually active with WOCBP must agree to follow instructions formethod(s) of before study entry, for all the duration of the study and for at least 16weeks after the last dose of investigational drug (90 days for sperm turnover plus thetime required for the active metabolite of sunitinib to undergo five half-lives).

Exclusion

Exclusion Criteria:

  1. untreated CNS metastases. Patients with treated brain metastases are eligible if theyare clinically stable with regard to neurologic function, off steroids after cranialirradiation (whole brain radiation therapy, focal radiation therapy, and stereotacticradiosurgery) ending at least 2 weeks prior to start of treatment, or after surgicalresection performed at least 28 days prior to start of treatment. The patient may haveno evidence of Grade ≥1 CNS haemorrhage based on pre-treatment Magnetic ResonanceImaging (MRI) or IV contrast CT scan (performed within 28 days before start oftreatment)
  2. Major surgery, other than diagnostic surgery, within 4 weeks prior to treatment
  3. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemictherapy
  4. Pregnant or breast feeding women
  5. Previous (within the last 5 years) or current malignancies at other sites, except foradequately treated basal cell or squamous cell skin cancer or in situ carcinoma of thecervix uteri
  6. Current enrollment in or participation in another therapeutic clinical trial within 4weeks before treatment start.
  7. Patients with uncontrolled or significant cardiovascular disease (AMI within 12months, unstable angina within 6 months, NYHA (New York Heart Association) Class III,IV Congestive heart failure or left ventricular ejection fraction below localinstitutional lower limit of normal or below 45%,
  8. Ongoing symptomatic cardiac dysrhythmias, uncontrolled atrial fibrillation, orprolongation of the Fridericia corrected QT (QTcF) interval defined as > 450 msec formales and > 470 msec for females, where QTcF = QT / 3√RR
  9. Poorly controlled hypertension
  10. History of cerebrovascular accident including transient ischemic attack within thepast 12 months.
  11. History of deep vein thrombosis (DVT) unless adequately treated with low molecularweight heparin
  12. History of pulmonary embolism within the past 6 months unless stable, asymptomatic,and treated with low molecular weight heparin for at least 6 weeks.
  13. Evidence of active bleeding or bleeding susceptibility; or medically significanthemorrhage within prior 30 days.
  14. Receiving concomitant CYP3A4 inducers or strong CYP3A4 inhibitors
  15. Impairment of gastrointestinal function or gastrointestinal disease that maysignificantly alter the absorption of sunitinib
  16. Known HIV infection

Study Design

Total Participants: 56
Study Start date:
March 02, 2017
Estimated Completion Date:
May 31, 2022

Study 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

Connect with a study center

  • National Cancer Institute

    Milan, 20133
    Italy

    Active - Recruiting

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