Pazopanib and Weekly Topotecan in Patients Recurrent Ovarian Cancer (TOPAZ)

NCT01600573 | Unknown Phase 1

• 1 other identifier: PazTo_2010
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial shall clarify the efficacy and safety of pazopanib in combination with weekly topotecan in patients with platinum-resistant or intermediate platinum-sensitive recurrent epithelial ovarian cancer, fallopian and peritoneal carcinoma

Conditions

Ovarian Cancer

Keywords

ovarian cancer

Outcome Measures

Primary Outcomes (2)

• Phase I: Assessment of dose-limiting toxicity in order to determine the maximum tolerated dose (MTD) of pazopanib in combination with weekly topotecan

  Dose-limiting toxicities are defined as follows: * grade 3 or 4 non-hematologic toxicity other than nausea or vomiting * grade 3 or 4 thrombocytopenia (platelet count less than 50000/µl) * grade 4 neutropenia lasting ≥ 7 days or febrile neutropenia defined as ANC \<1000/µl concurrent with fever * Any grade 2 and more toxicity of cycle 1 other than nausea, vomiting, rash, alopecia or anemia, that persisted over 35 days.

  after 4 weeks

• • Phase II: Progression-free survival according to RECIST criteria

  • Phase II: Progression-free survival according to RECIST criteria

  up to 3.5 years

Secondary Outcomes (8)

• • Overall survival

  up to 3.5 years

• • Response rate (CR, PR) according to RECIST criteria

  up to 3.5 years

• • Clinical benefit rate (CR, PR, SD)

  up to 3.5 years

• • Duration of response

  up to 3.5 years

• • Time to progression (TTP)

  up to 3.5 years

Study Arms (1)

pazopanib plus weekly topotecan

EXPERIMENTAL

pazopanib in combination with weekly topotecan

Drug: pazopanib in combination with weekly topotecan

Interventions

pazopanib in combination with weekly topotecan DRUG

* Topotecan as an IV infusion over 30 minutes on days 1, 8, and 15 of a 28 day cycle and * Pazopanib orally once daily continuous dosing in the following dose levels: Phase I Trial: Dose level -I: Topotecan weekly 3mg/m2, Pazopanib 400 mg Dose level I: Topotecan weekly 4mg/m2, Pazopanib 400 mg Dose level II: Topotecan weekly 4mg/m2, Pazopanib 600 mg Dose level III: Topotecan weekly 4mg/m2, Pazopanib 800 mg Phase II Trial: Phase II will either use the MTD as determined in Phase I or a lower dose if deemed necessary.

Also known as: pazopanib in combination with weekly topotean

pazopanib plus weekly topotecan

Eligibility Criteria

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

You may qualify if:

• written informed consent
• histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal carcinoma or fallopian tube cancer
• platinum resistant (recurrence within 6 months of a platinum-containing regimen) or platinum refractory (progression during platinum treatment) or intermediate platinum-sensitive (recurrence within 12 months after a platinum-based primary therapy) disease
• no more than 2 prior treatment regimens for epithelial ovarian cancer
• Age more than 18 years
• ECOG of 0 or 1
• adequate organ function
• measurable disease or evaluable disease according to RECIST criteria
• able to swallow and retain oral medication
• life expectancy of at least 12 weeks
• non-childbearing potential or negative serum pregnancy test of women of childbearing potential and agrees to use adequate contraception for 14 days before exposure to investigational product, through the dosing period, and for at least 6 months after the last dose of investigational product. Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.

You may not qualify if:

• prior malignancies; subject who have had another malignancy and have been disease-free for 5 years which effect progression free survival, or subject with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) is required only if clinically indicated or if the subject has a history of CNS metastases.
• clinically significant gastrointestinal abnormalities that might interfere with oral dosing or that may increase the risk for gastrointestinal bleeding
• clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
• Grade 3 or 4 diarrhoea
• Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy)
• poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg\]
• Prolongation of corrected QT interval (QTc) \>450 milliseconds using Bazett's formula
• History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting; myocardial infarction; unstable angina; symptomatic peripheral vascular disease; coronary artery by-pass graft surgery
• Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
• History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
• Macroscopic hematuria
• Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug
• Evidence of active bleeding or bleeding diathesis
• known endobronchial lesions and/or lesions infiltrating major pulmonary vessels and/or involvement of large pulmonary vessels by tumor

Sponsors & Collaborators

• JSehouli: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Charité Campus Virchow-Klinikum

Berlin, 13353, Germany

RECRUITING

Related Publications (1)

• Chekerov R, Arndt T, Pietzner K, Canzler U, Wimberger P, Strauss HG, Mahner S, Woelber L, de Gregorio N, Stocker G, von Abel E, Neunhoeffer T, Belau AK, Mustea A, Yalinkaya I, Braicu EI, Richter R, Sehouli J; NOGGO ovarian cancer study group. Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer: results of a multicentre, open label phase I/II study (TOPAZ). J Cancer Res Clin Oncol. 2023 Aug;149(10):7637-7649. doi: 10.1007/s00432-023-04647-9. Epub 2023 Mar 31.

  PMID: 37000264 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• jalid Sehouli, Prof. Dr.

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jalid Sehouli, Prof. Dr.

CONTACT

+49 (0) 30 450; jalid.sehouli@charite.de

Radoslav Chekerov, Dr.

CONTACT

030/450; radoslav.chekerov@charite.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. Jalid Sehouli

Study Record Dates

• First Submitted: May 9, 2012
• First Posted: May 17, 2012
• Study Start: May 1, 2012
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: October 11, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)