Phase I/II Study of Pazopanib and Cyclophosphamide in Patients With Platinum-resistant Recurrent Ovarian Cancer

Epithelial Ovarian Cancer Clinical Trial

Official title:

A Phase I/II Study of Pazopanib (GW786034) and Cyclophosphamide in Patients With Platinum-resistant Recurrent, Pre-treated Ovarian Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01238770
• Other study ID #: 3107000
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 10, 2010
• Last updated: February 8, 2016
• Start date: November 2010
• Est. completion date: October 2015

Study information

• Verified date: February 2016
• Source: University Hospital Heidelberg
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The current trial shall clarify the potential of the multitarget antiangiogenic tyrosinkinase inhibitor GW 786034 (pazopanib) in combination with oral cyclophosphamide as salvage treatment in patients with recurrent, pretreated ovarian cancer.

Description:

This study is a prospective open-label, non-randomized multicenter phase I/II trial in order to determine overall response rate of patients with platinum-resistant or refractory recurrent, pretreated epithelial ovarian cancer.

In order to assure adequate toxicity assessment, a phase-I-trial is proponed. Phase II will be performed with MTD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Written informed consent

2. Female subjects =18 years of age

3. Histologically or cytologically confirmed diagnosis of: epithelial ovarian cancer which is platinum resistant or platinum refractory,cancer of the fallopian tube, peritoneal cancer

4. Patients must have failed available standard chemotherapy regimen

5. Prior treatment with at least 2 chemotherapy regimens in advanced tumor setting

6. Performance status ECOG 0 - 2

7. Adequate contraception

8. Adequate organ function

9. Measurable disease according to RECIST criteria.

10. Able to swallow and retain oral medication.

11. Life expectancy of at least 12 weeks.

Exclusion Criteria:

1. Any second malignancy within the last 5 years, with the exception of basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri

2. 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.

3. Clinically significant gastrointestinal abnormalities which might interfere with oral dosing

4. Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy).

5. Prolongation of corrected QT interval (QTc) >480 msecs.

6. 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 II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)

• History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months

7. Macroscopic hematuria

8. Hemoptysis that is clinically relevant within 4 weeks of first dose of study drug

9. Evidence of active bleeding or bleeding diathesis

10. Known endobronchial lesions or involvement of large pulmonary vessels by tumor

11. Prior major surgery or trauma within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.

12. Chemotherapy or radiation therapy within 2 weeks prior to the first dose of study drug.

13. Biological therapy, hormonal therapy or treatment with an investigational agent within 28 days or 5 half-lives

14. Prior antiangiogenic therapy.

15. Is unable or unwilling to discontinue predefined prohibited medications listed in the protocol for 14 days or five half-lives of a drug (whichever is longer) prior to Visit 1 and for the duration of the study

16. Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity.

17. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib

18. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

19. Pregnancy

20. More than 3 different chemotherapy regimens in advanced tumor setting

21. Uncontrolled hypertension

22. History of ischemic event (stroke, myocardial infarction, unstable angina, TIA, symptomatic peripheral vascular disease)

23. History or clinical evidence of thrombo-embolic event

24. History of haemoptysis, cerebral, or clinically significant gastrointestinal haemorrhage in the past 6 months

25. Active bleeding

26. Signs/Suspicion of intestinal obstruction

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epithelial Ovarian Cancer
• Neoplasms, Glandular and Epithelial
• Ovarian Neoplasms

Intervention

Drug:
• Pazopanib
Phase I Cyclophosphamid Pazopanib Dose level I 50 mg/day 400 mg/day Dose level II 50 mg/day 600 mg/day Dose level III 50 mg/day 800 mg/day Cyclophosphamide 50 mg daily orally Pazopanib 400, 600 or 800 mg daily orally Phase II: Cyclophosphamide 50 mg daily orally Pazopanib 400, 600 or 800 mg daily orally The dose for the phase II part of the trial will be based on the MTD of phase I.

Locations

Country	Name	City	State
Germany	Marienkrankenhaus Hamburg	Hamburg
Germany	Universitäts-Frauenklinik	Heidelberg
Germany	Klinikum Konstanz Gynäkologie und Geburtshilfe	Konstanz
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz Klinik und Poliklinik für Geburtshilfe und Frauenheilkunde	Mainz
Germany	Universitätsfrauenklinik Tübingen Klinik für Gynäkologie und Geburtshilfe	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
Priv.-Doz. Dr. med. Joachim Rom

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the optimal doses for pazopanib (phase I)		42 months	Yes
Primary	Overall response rate according to RECIST criteria / clinical benefit (stable disease or partial response or complete response) (phase II)		12 weeks after start of treatment	No
Secondary	Time to progression (TTP) according to RECIST criteria		7 years	No
Secondary	Overall survival		7 years	Yes
Secondary	Evaluation of CA125 tumour response		7 years	No
Secondary	Number of patients with Adverse Events		7 years	Yes
Secondary	Assessment of quality of life over time as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire		7 years	No