Randomized Multicenter Trial With SU11248 Evaluating Dosage,Tolerability,Toxicity and Effectiveness of a Multitargeted Receptor Tyrosine Kinase Inhibitor

NCT00543049 | Completed Phase 2

• 1 other identifier: AGO-OVAR 2.11
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 16

Brief Summary

Ovarian cancer is most often recognized in advanced clinical state, the initial therapeutic strategies consist of a platinum containing chemotherapy subsequent to primary surgery. Although initially responsive to platinum-paclitaxel containing chemotherapy, a significant number of patients will show tumor progression during first line chemotherapy or relapse within six months after completion of first line chemotherapy, therefore being characterized as chemotherapy resistant. Any second line chemotherapy will result in approximately 10% of overall response, underlining the poor prognosis for these patients with an estimated median overall survival of 20 weeks. In addition to conventional chemotherapeutics, so called small molecules are of high interest to establish new strategies in chemotherapy-refractory ovarian cancer (and in the long run first line chemotherapy). SU11248 is a polytargeting tyrosine kinase inhibitor. SU11248 has demonstrated clinical efficacy in kidney cancer and GIST, further clinical trials have been initiated in other tumor entities. Growth pattern and biological targets present in ovarian cancer indicate that SU11248 might be a promising compound for the treatment of ovarian cancer. Especially, VEGFR, PDGFR and c-kit are specific targets for SU11248, which are expressed in ovarian cancer. The different targets of SU11248 provide a potential advantage of this compound compared to single-target molecules in chemotherapy-refractory ovarian cancer.

Conditions

Platinum Refractory Epithelial Ovarian Cancer; Primary Cancer of the Peritoneum; Cancer of the Fallopian Tube

Keywords

platinum refractory; epithelial ovarian cancer; primary cancer of the peritoneum; cancer of the fallopian tube

Outcome Measures

Primary Outcomes (1)

• objective response rate

  one year

Secondary Outcomes (1)

• tolerability and toxicity, overall survival, duration of response, time to progression, stable disease

  one year

Study Arms (2)

1 non-continuous

OTHER

Subjects will receive open-label sunitinib = SU11248 at a dose of 50.0 mg once daily. After 28 days, treatment will be paused for 14 days and cycle one is completed, followed by resumption of therapy as cycle one for up to one year (therapy can be continued in case of tumor response and benefit for the patient for more than one year).

Drug: Sunitinib

2 continuous

OTHER

Subjects will receive open-label sunitinib = SU11248 at a dose of 37.5 mg once daily continuously. Treatment period up to one year (therapy can be continued in case of tumor response and benefit for the patient for more than one year).

Drug: SUNITINIB

Interventions

SUNITINIB DRUG

Sunitinib, oral, 50mg once daily, 28 days then paused for 14 days, for up to one year

Also known as: Sutent, Sunitinib, SU011248

1 non-continuous

Eligibility Criteria

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

You may qualify if:

• Women, 18 years and older, written (signed and dated) informed consent
• Histological confirmed epithelial ovarian cancer, primary cancer of the peritoneum or fallopian tube
• Up to three prior chemotherapies, at least one platinum based chemotherapy
• Platinum refractory or resistant ovarian cancer (defined as stable (SD) or progressive disease (PD) during platinum containing chemotherapy, or treatment free interval \< 6 months after stop of platinum based chemotherapy)
• Measurable or non-measurable disease
• Elevated CA°125 level (\> 2 x ULN in case of normal CA°125 after prior chemotherapy; or ≥ 2 x nadir CA°125 value after prior chemotherapy, when CA° 125 levels remained elevated above normal) in case of non-measurable disease
• ECOG performance status 0-2
• Negative pregnancy test within 5 days before randomization and adequate contraception in women with childbearing potential
• Adequate organ function as defined by the following criteria:
• Serum aspartate aminotransferase (AST; serum glutamate-oxalate transferase \[SGOT\]) and serum alanine aminotransferase (ALT; serum glutamate-pyruvate transferase \[SGPT\]) \<=2.5 x upper limit of normal (ULN). If liver function abnormalities are due to underlying malignancy, then AST and ALT may be \<=5x ULN
• Total serum bilirubin \<=1.5 x ULN
• Prothrombin time (PT) and partial thromboplastin time (PTT) \<=1.5 x ULN
• Serum albumin \>= 3.0 g/dL
• Absolute neutrophil count (ANC) \>=1500/µl
• Platelets \>=100,000/µl

You may not qualify if:

• Borderline tumor of the ovaries
• Acute or chronic infection
• Any required concurrent cancer chemotherapy or antineoplastic endocrine therapy or radiotherapy
• Exposure to investigational trial medication, cancer chemo- or radiotherapy within the last 28 days prior to start of study treatment
• Known or suspected hypersensitivity to investigational compound
• Second malignancy interfering with prognosis of the patient
• Cachectic patients with a body weight \<45 kg
• Patients requiring parenteral nutrition
• Patients with ileus within the last 28 days
• Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event
• Current treatment with therapeutic doses of anticoagulant
• Current treatment with CYP3A4 inhibitors or -inducers
• Hypertension that cannot be controlled by medications (\>150/100 mmHg despite optimal medical therapy)
• Ongoing cardiac dysrhythmias of NCI CTCAE grade \>=2, atrial fibrillation of any grade, or prolongation of the QTc interval to \>470 msec for females
• Left ventricular ejection fraction (LVEF) \<=50% as measured by echocardiogram

Sponsors & Collaborators

• AGO Study Group: lead
• Philipps University Marburg: collaborator
• HSK Reasearch GmbH Wiesbaden: collaborator

Study Sites (16)

Malterser-Krankenhaus Bonn-Rhein/Sieg, Frauenklinik

Bonn, 53123, Germany

Location

Klinikum Bremen-Mitte gGmbH, Frauenklinik

Bremen, 28177, Germany

Location

Universitätsklinikum Carl Gustav Carus, Klinik u. Poliklinik für Frauenheilkunde und Geburtshilfe

Dresden, 01307, Germany

Location

Universitätsklinikum, Universitätsfrauenklinik

Essen, 45122, Germany

Location

Klinikum der JWG Universität Frankfurt, Universitätsfrauenklinik

Frankfurt am Main, 60591, Germany

Location

Universitätsklinikum Freiburg, Department Universitäts-Frauenklinik

Freiburg im Breisgau, 79106, Germany

Location

Klinikum der Ernst-Moritz-Universität, Klinik u. Poliklinik für Gyn. - u. Geb.Hilfe

Greifswald, 17487, Germany

Location

Med. Hochschule Hannover, Frauenklinik

Hanover, 30625, Germany

Location

St. Vincentius Kliniken AG, Frauenklinik

Karlsruhe, 76135, Germany

Location

Universitätsklinikum Schleswig-Holstein Campus Kiel, Klinik f. Gynäkologie u. Geburtshilfe

Kiel, 24105, Germany

Location

Otto-von-Guericke-Universität, Klinik für Frauenheilkunde und Geburtshilfe

Magdeburg, 39108, Germany

Location

Universitätsklinikum Gießen u. Marburg, Standort Marburg, Klinik f. Gynäkologie, Gyn. Endokrinologie u. Onkologie

Marburg, 35043, Germany

Location

Elblandkliniken Meißen-Radebeul GmbH, Gynäkologie

Radebeul, 01445, Germany

Location

Universitätsklinikum Tübingen, Frauenklinik

Tübingen, 72076, Germany

Location

Universitätsklinikum, Universitätsfrauenklinik

Ulm, 89075, Germany

Location

Dr. Horst Schmidt Kliniken GmbH, Klinik f. Gynäkologie u. Gyn. Onkologie

Wiesbaden, 65199, Germany

Location

Related Publications (2)

• Baumann KH, du Bois A, Meier W, Rau J, Wimberger P, Sehouli J, Kurzeder C, Hilpert F, Hasenburg A, Canzler U, Hanker LC, Hillemanns P, Richter B, Wollschlaeger K, Dewitz T, Bauerschlag D, Wagner U. A phase II trial (AGO 2.11) in platinum-resistant ovarian cancer: a randomized multicenter trial with sunitinib (SU11248) to evaluate dosage, schedule, tolerability, toxicity and effectiveness of a multitargeted receptor tyrosine kinase inhibitor monotherapy. Ann Oncol. 2012 Sep;23(9):2265-2271. doi: 10.1093/annonc/mds003. Epub 2012 Feb 29.

  PMID: 22377563 RESULT

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Uwe Wagner, MD, PhD

  Universitätsklinikum Gießen u. Marburg, Klinik f. Gynäkologie, Gyn. Endokrinologie u. Onkologie

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 10, 2007
• First Posted: October 12, 2007
• Study Start: September 1, 2007
• Primary Completion: June 1, 2012
• Last Updated: March 7, 2014

Record last verified: 2014-03

Locations

DE (16)