A Study of Axitinib in Patients With Advanced Angiosarcoma and Other Soft Tissue Sarcomas

NCT01140737

Last updated date
Study Location
Aberdeen Royal Infirmary
Aberdeen, Scotland, , United Kingdom
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Soft Tissue Sarcoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
16 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Pathologically confirmed soft tissue sarcoma, including:

- Angiosarcoma, including intermediate and malignant vascular tumours (WHO classification, 2002) and Kaposi's sarcoma.

- Leiomyosarcoma, including uterine, skin or non organ origin.

- Synovial sarcoma.

- Other eligible subtypes of soft tissue sarcoma of Trojani intermediate or high grade, including fibroblastic, fibrohistiocytic, adipocytic, rhabdomyosarcoma, malignant peripheral nerve sheath, and not otherwise specified. See exclusion criteria for ineligible subtypes.

- Locally advanced or metastatic disease incurable by surgery or radiotherapy.

- Measurable disease according to RECIST criteria.

- Evidence of objective disease progression in the past 6 months, without anticancer treatment since progression.

- Patients ineligible for chemotherapy (eg. through age, clinical condition or patient refusal) or who have received no more than two prior chemotherapy regimens.

- Age >or = 16.

- WHO performance status 0, 1 or 2.

- At least 4 weeks from prior anticancer treatment (surgery, radiotherapy and systemic therapies) and full recovery from all their adverse effects.

- No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be < or = 140 mm Hg, and the baseline diastolic blood pressure readings must be < or = 90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.

- Adequate physiological function:

- renal : calculated or measured creatinine clearance > or = 50 ml/min using the Cockcroft-Gault formula (see appendix 5).

- haematological: Absolute Neutrophil Count (ANC) > or = 1.5 x 109/L, platelets > or = 100 x 109/L, International Normalized Ratio (INR) < or = 1.2.

- hepatic: bilirubin within normal range, AST and ALT < or = 3 x upper limit of normal.

- cardiac: Left Ventricular Ejection Fraction (LVEF) measured by Echocardiogram or Multi Gated Acquisition Scan (MUGA) within normal range.

- Urinary protein <2+ by urine dipstick. If dipstick is >2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours.

- Negative pregnancy test and agrees to comply with contraceptive measures

- Able to swallow oral medication.

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Ineligible pathological subtypes including:


- Osteosarcoma


- Ewings/Primitive Neuroectodermal Tumour (PNET sarcomas)


- Chondrosarcoma


- Gastrointestinal stromal tumours (GIST)


- Dermatofibrosarcoma protuberans (DFSP)


- Malignant mesothelioma


- Mixed mesodermal tumours of uterus


- Known central nervous system metastases.


- Age < 16.


- Current use or anticipated need for treatment with drugs that are known CYP3A4 or
CYP1A2 inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole,
phenobarbital, phenytoin, primidone, rifabutin, rifampicin, and St. John"s Wort).


- Current use or anticipated need for treatment with drugs that are known potent CYP3A4
inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole,
voriconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir,
ritonavir, nelfinavir and lopinavir).


- Previous malignancies (except curatively treated non-melanoma skin cancer or carcinoma
in situ of the cervix or breast) within the past 3 years.


- Heart failure > or = New York Heart Association (NYHA) class II.


- History within the previous 6 months of any blood clots in the sputum or streaky
haemoptysis that was persistent (> 2 weeks) or recurrent (> 3 episodes).


- Patients with cavitating lung metastases or any metastasis abutting or invading a
major pulmonary blood vessel on baseline CT or MRI scan.


- History of bleeding diathesis or coagulopathy within 12 months of study entry


- Any of the following within the 12 months prior to trial drug administration:
myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident or transient
ischemic attack, deep vein thrombosis or pulmonary embolism.


- Therapeutic dose warfarin. Low molecular weight heparin is permitted.


- Regular treatment with antiplatelet medication, including aspirin >325 mg/day or
NSAIDs


- History of malabsorption or major gastrointestinal tract resection likely to affect
trial drug absorption.


- Pregnancy or breastfeeding. Female patients must be surgically sterile or be
postmenopausal, or must agree to use two effective contraception measures during the
period of therapy which should be continued for 4 weeks after the last dose of trial
therapy. Male patients must be surgically sterile or must agree to use effective
contraception during the period of therapy which should be continued for 4 weeks after
the last dose of trial therapy . The definition of effective contraception will be
based on the judgment of the Investigator or designee.

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Soft Tissue SarcomaA Study of Axitinib in Patients With Advanced Angiosarcoma and Other Soft Tissue Sarcomas
NCT01140737
  1. Aberdeen, Scotland
  2. Edinburgh, Scotland
  3. Bristol,
  4. Leeds,
  5. London,
  6. London,
  7. London,
  8. Manchester,
  9. Nottingham,
  10. Oxford,
  11. Sheffield,
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Advanced Information
Descriptive Information
Brief Title  ICMJE A Study of Axitinib in Patients With Advanced Angiosarcoma and Other Soft Tissue Sarcomas
Official Title  ICMJE A Clinicopathological Phase II Study of Axitinib in Patients With Advanced Angiosarcoma and Other Soft Tissue Sarcomas
Brief Summary The study objective is to evaluate the therapeutic activity, safety and tolerability of axitinib in patients with advanced/metastatic soft tissue sarcoma who are unsuitable for or have relapsed after standard chemotherapy. The therapeutic activity will be separately assessed in angiosarcoma, synovial sarcoma, leiomyosarcomas and other sarcomas.
Detailed Description

Soft tissue sarcomas are a heterogeneous group of rare malignancies that account for 0.72% of new malignancies and 0.65% of malignant deaths. Advanced sarcomas carry a poor prognosis. Angiogenesis is a hallmark of tumour growth, and there is increasing evidence that antiangiogenic drugs, including axitinib, can lead to tumour regression and improve patient survival in a variety of tumours.

Patients with angiosarcoma, synovial sarcoma, leiomyosarcoma and other sarcomas will be separately evaluated.

Patients will take axitinib 5mg tablets by mouth twice daily. This will be continued for 2 years or until disease progression, or development of limiting toxicity. In the event of severe toxicity, axitinib will be stopped until the toxicity has improved. Treatment may be interrupted for a maximum of 2 weeks. Following this, axitinib can be restarted at a lower dose of 3 mg twice daily. If the toxicity has not improved sufficiently, axitinib will be permanently stopped.

Patients will be monitored once weekly for the first month, then at 4 week intervals. Toxicity will be closely monitored. At each clinic visit, patients will have a physical examination and a routine blood test. A Chest x-ray, CT and/or MRI scans will be done before study entry, then every 12 weeks and at the end of treatment. Disease evaluation will be carried out 12 weeks after study entry, then every 12 weeks until disease progression. After disease progression, patients will be followed up every 3 months for survival. Patients will be followed up until death or a minimum follow up period of 1 year.

Patients will be enrolled from hospitals all over the UK.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Soft Tissue Sarcoma
Intervention  ICMJE Drug: Axitinib
Patients will take axitinib tablets 5 mg by mouth twice daily continuously. There may be one dose reduction to 3mg twice daily. A four week dosing period will be considered as 1 cycle of treatment. Axitinib treatment will be continued until disease progression, or the development of limiting toxicity.
Other Name: AG-013736
Study Arms  ICMJE Experimental: Axitinib
Patients will take axitinib tablets 5 mg by mouth twice daily continuously. There may be one dose reduction to 3mg twice daily.
Intervention: Drug: Axitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: April 19, 2016)
145
Original Estimated Enrollment  ICMJE
 (submitted: June 8, 2010)
152
Estimated Study Completion Date  ICMJE December 2018
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Pathologically confirmed soft tissue sarcoma, including:

    • Angiosarcoma, including intermediate and malignant vascular tumours (WHO classification, 2002) and Kaposi's sarcoma.
    • Leiomyosarcoma, including uterine, skin or non organ origin.
    • Synovial sarcoma.
    • Other eligible subtypes of soft tissue sarcoma of Trojani intermediate or high grade, including fibroblastic, fibrohistiocytic, adipocytic, rhabdomyosarcoma, malignant peripheral nerve sheath, and not otherwise specified. See exclusion criteria for ineligible subtypes.
  • Locally advanced or metastatic disease incurable by surgery or radiotherapy.
  • Measurable disease according to RECIST criteria.
  • Evidence of objective disease progression in the past 6 months, without anticancer treatment since progression.
  • Patients ineligible for chemotherapy (eg. through age, clinical condition or patient refusal) or who have received no more than two prior chemotherapy regimens.
  • Age >or = 16.
  • WHO performance status 0, 1 or 2.
  • At least 4 weeks from prior anticancer treatment (surgery, radiotherapy and systemic therapies) and full recovery from all their adverse effects.
  • No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be < or = 140 mm Hg, and the baseline diastolic blood pressure readings must be < or = 90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
  • Adequate physiological function:

    • renal : calculated or measured creatinine clearance > or = 50 ml/min using the Cockcroft-Gault formula (see appendix 5).
    • haematological: Absolute Neutrophil Count (ANC) > or = 1.5 x 109/L, platelets > or = 100 x 109/L, International Normalized Ratio (INR) < or = 1.2.
    • hepatic: bilirubin within normal range, AST and ALT < or = 3 x upper limit of normal.
    • cardiac: Left Ventricular Ejection Fraction (LVEF) measured by Echocardiogram or Multi Gated Acquisition Scan (MUGA) within normal range.
    • Urinary protein <2+ by urine dipstick. If dipstick is >2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours.
  • Negative pregnancy test and agrees to comply with contraceptive measures
  • Able to swallow oral medication.

Exclusion Criteria:

  • Ineligible pathological subtypes including:

    • Osteosarcoma
    • Ewings/Primitive Neuroectodermal Tumour (PNET sarcomas)
    • Chondrosarcoma
    • Gastrointestinal stromal tumours (GIST)
    • Dermatofibrosarcoma protuberans (DFSP)
    • Malignant mesothelioma
    • Mixed mesodermal tumours of uterus
    • Known central nervous system metastases.
    • Age < 16.
    • Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampicin, and St. John"s Wort).
  • Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, voriconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir and lopinavir).
  • Previous malignancies (except curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix or breast) within the past 3 years.
  • Heart failure > or = New York Heart Association (NYHA) class II.
  • History within the previous 6 months of any blood clots in the sputum or streaky haemoptysis that was persistent (> 2 weeks) or recurrent (> 3 episodes).
  • Patients with cavitating lung metastases or any metastasis abutting or invading a major pulmonary blood vessel on baseline CT or MRI scan.
  • History of bleeding diathesis or coagulopathy within 12 months of study entry
  • Any of the following within the 12 months prior to trial drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism.
  • Therapeutic dose warfarin. Low molecular weight heparin is permitted.
  • Regular treatment with antiplatelet medication, including aspirin >325 mg/day or NSAIDs
  • History of malabsorption or major gastrointestinal tract resection likely to affect trial drug absorption.
  • Pregnancy or breastfeeding. Female patients must be surgically sterile or be postmenopausal, or must agree to use two effective contraception measures during the period of therapy which should be continued for 4 weeks after the last dose of trial therapy. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy which should be continued for 4 weeks after the last dose of trial therapy . The definition of effective contraception will be based on the judgment of the Investigator or designee.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01140737
Other Study ID Numbers  ICMJE STH15195
2008-006007-23 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party Sheffield Teaching Hospitals NHS Foundation Trust
Study Sponsor  ICMJE Sheffield Teaching Hospitals NHS Foundation Trust
Collaborators  ICMJE
  • University of Birmingham
  • Cancer Research UK
  • Pfizer
Investigators  ICMJE
Principal Investigator:Penella Woll, BMedSciWeston Park Hospital, Sheffield, UK
PRS Account Sheffield Teaching Hospitals NHS Foundation Trust
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP