[18F]Fluciclatide-PET, Pazopanib and Paclitaxel in Ovarian Cancer (PAZPET-1)

Phase 1b Exploratory Study of [18F]Fluciclatide-PET as a Marker of Angiogenic Response to Combination Therapy With the Pan-VEGF Inhibitor, Pazopanib, and Weekly Paclitaxel in Platinum Resistant Ovarian Cancer

The purpose of this study is to assess [18F] -fluciclatide as a biomarker of response to pazopanib and to evaluate the efficacy and safety of the combination of pazopanib and paclitaxel in platinum-resistant ovarian cancer patients.

Study Overview

• Status: Completed
• Conditions: Ovarian Neoplasm
• Intervention / Treatment: Drug: Pazopanib and paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Imperial College Healthcare NHS Trust
  • Southend, United Kingdom
    • Southend University Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age ≥ 18 years
• Diagnosis of relapsed ovarian cancer
• Responded to at least on one line of prior platinum based therapy
• Relapsed within platinum resistant interval (≤6months)
• Eastern Cooperative Oncology Group (ECOG) performance status of <2
• Measurable disease defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥25mm using conventional techniques

• Satisfactory baseline haematologic and organ function:

  • Haematologic: Absolute neutrophil count > or = 1.5 X 10^9/L; Platelets > or = 100 X 10^9/L; Haemoglobin > or = 9g/dL; PT or INR < or = 1.2 x ULN; PTT < or = 1.2 x ULN
  • Hepatic: Bilirubin < or = 1.5 X ULN; AST or ALT < or = 2.5 X ULN
  • Renal: Serum creatinine < or = 1.5 mg/dL; Or if >1.5 mg/dL, calculated creatinine clearance > or = 50mL/min; UPC <1

Exclusion Criteria:

• Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the study.

• Treatment with any of the following anti-cancer therapies:

  • radiation therapy 28 days prior to the first dose of pazopanib OR
  • surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR
  • chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
• Treatment with anti-angiogenic therapy
• Presence of gross ascites
• Clinically significant peripheral neuropathy
• Females of childbearing potential who are unwilling to avoid pregnancy, for the duration of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pazopanib and paclitaxel	Drug: Pazopanib and paclitaxel; Pazopanib 800mg od for 7 days, followed by 18 weeks of combination therapy (paclitaxel 80mg/m2 weekly and pazopanib 800mg od). Following the completion of combination therapy, patients will continue on maintenance pazopanib 800mg od until disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of change in [18F]-fluciclatide retention parameters following 1 week of pazopanib treatment	Semi-quantitative standardized uptake value and fully quantitative net irreversible plasma to tumour transfer constant	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of women who experience side effects from the combination of paclitaxel and pazopanib	Core study assessments including physical examination, vital signs, ECG, and adverse event reporting	12 months
The proportion of patients responding to combination paclitaxel and pazopanib		12 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: GlaxoSmithKline
• Investigators: Study Director: Rohini Sharma, MD, Imperial College London; Principal Investigator: Timothy Crook, MD, Southend University Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: March 22, 2012
• First Submitted That Met QC Criteria: May 25, 2012
• First Posted (Estimate): May 30, 2012

Study Record Updates

• Last Update Posted (Actual): March 10, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: ovarian cancer; platinum resistant
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: CRO1627