Pazopanib/Doxil in Adv Relapsed Plat Sensitive or Resistant Ovarian, Fallopian or Primary Peritoneal Adenocarcinoma

NCT01035658 | Terminated Phase 1 Results

• 1 other identifier: SCRI GYN 26
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

Brief Summary

In this study, patients with relapsed or refractory ovarian cancer will receive treatment with pazopanib and liposomal doxorubicin (Doxil) until disease progression or unacceptable toxicity occurs. The Phase I portion will define the dose limiting toxicity (DLT) of pazopanib and liposomal doxorubicin when administered in combination. Once the maximum tolerated dose has been identified in the Phase I portion, the Phase II portion will evaluate efficacy and safety of this combination in the same patient population.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Carcinoma

Keywords

Pazopanib; Doxil; Liposomal doxorubicin; Advanced relapsed; platinum-sensitive; platinum-resistant

Outcome Measures

Primary Outcomes (3)

• Phase I: Maximum Tolerated Dose (MTD) of Pazopanib and Liposomal Doxorubicin

  The MTD of the drug combination will be determined as the highest dose at which ≤1 of 6 subjects experiences a Grade 3 or Grade 4 DLT according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.

  18 months

• Phase I - Dose Limiting Toxicities

  As requested, this outcome measure reports the number of patients experiencing dose limiting toxicities (DLTs) in the Phase I portion of the study

  18 months

• Phase II: Progression Free Survival

  Defined as from date of randomization until objective tumor progression or death. Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) and CA-125 response in patients using the Rustin Criteria.

  18 months

Secondary Outcomes (3)

• Phase II - Overall Survival of Patients With Relapsed/Refractory Ovarian Cancer Following Treatment With Pazopanib and Liposomal Doxorubicin

  18 months

• Response Rate in the Subsets of Patients With Platinum-sensitive and Platinum-refractory Ovarian Carcinoma

  18 months

• Number of Participants Experiencing Adverse Events With the Combination of Pazopanib and Liposomal Doxorubicin Doses

  18 months

Study Arms (4)

Dose Level 1

EXPERIMENTAL

Systemic therapy with pazopanib and liposomal doxorubicin (Doxil). Single-agent pazopanib will be given for a 7 day run-in period, followed by a combination of pazopanib (400mg) and liposomal doxorubicin (40mg) administered in 28-day treatment cycles. Cycles will continue until disease progression, unacceptable toxicity or withdrawal.

Drug: Pazopanib; Drug: Doxil

Dose Level -1

EXPERIMENTAL

Systemic therapy with pazopanib and liposomal doxorubicin (Doxil). Single-agent pazopanib will be given for a 7 day run-in period, followed by a combination of pazopanib (400mg) and liposomal doxorubicin (30mg) administered in 28-day treatment cycles. Cycles will continue until disease progression, unacceptable toxicity or withdrawal.

Drug: Pazopanib; Drug: Doxil

Dose Level 1 Sequential

EXPERIMENTAL

Systemic therapy with pazopanib and liposomal doxorubicin (Doxil). In this schedule, liposomal doxorubicin (30mg) was given on day 1, and pazopanib (400mg) was given days 3 - 26 of each 28 day cycle. Cycles will continue until disease progression, unacceptable toxicity or withdrawal.

Drug: Pazopanib; Drug: Doxil

Dose Level 2 Sequential

EXPERIMENTAL

Systemic therapy with pazopanib and liposomal doxorubicin (Doxil). In this schedule, liposomal doxorubicin (40mg) was given on day 1, and pazopanib (400mg) was given days 3 - 26 of each 28 day cycle. Cycles will continue until disease progression, unacceptable toxicity or withdrawal.

Drug: Pazopanib; Drug: Doxil

Interventions

Pazopanib DRUG

All patients will begin treatment with a 7-day run in period of single-agent pazopanib. Patients will receive pazopanib orally days 1-28 of a 28 day cycle.

Also known as: Systemic therapy

Dose Level -1; Dose Level 1; Dose Level 1 Sequential; Dose Level 2 Sequential

Doxil DRUG

Liposomal doxorubicin (Doxil) will be administered IV on day 1 of a 28-day treatment cycle

Also known as: Systemic therapy, Liposomal doxorubicin

Dose Level -1; Dose Level 1; Dose Level 1 Sequential; Dose Level 2 Sequential

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of epithelial ovarian carcinoma (FIGO Stage II to IV), primary peritoneal cancer or fallopian tube.
• One or 2 previous chemotherapy regimens for advanced ovarian cancer. At least one of these regimens must have contained a platinum agent.
• Patients who are platinum-resistant (relapse \<6 months after completing a platinum-containing regimen) or platinum sensitive (relapse ≥ 6 months after platinum-containing regimen) are eligible.
• Radiographically documented progression per RECIST criteria (version 1.1) or progression of CA-125 during or subsequent to the last chemotherapy regimen.
• Measurable disease (RECIST criteria) or evaluable disease with elevated CA-125 level. Patients with normal CT scans and elevated CA-125 levels as the only indication of disease are not eligible. ECOG performance status of 0 or 1.
• Normal left ventricular ejection fraction (LVEF) according to institutional standards.
• Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of a minor surgery (with the exception of portacath placement); at least 4 weeks must have elapsed from the time of a major surgery.
• Laboratory values as follows:
• Absolute neutrophil count (ANC) ≥1500/μL
• Hemoglobin (Hgb) ≥9g/dL. Patients may not have received RBC transfusions within 7 days of screening assessment.
• Platelets ≥100,000/L
• AST or ALT must be \<2.5 x ULN (concomitant elevations in bilirubin and AST/ALT \>1.0 x ULN are not permitted).
• Total bilirubin \<1.5 x the institutional ULN (if Gilberts syndrome, direct bilirubin ≤1.5 x ULN)
• International normalized ratio (INR) 1.2 and activated partial thromboplastin time (aPTT) 1.2 the ULN (except for patients receiving anti-coagulation therapy)
• Cr ≤ 1.5 x ULN. If Cr \>1.5 x ULN, then calculated creatinine clearance must be ≥50 mL/min

You may not qualify if:

• Patients may not have received either investigational or marketed agents, which act by primary anti-angiogenic mechanisms (i.e. bevacizumab).
• Prior treatment with liposomal doxorubicin.
• Patients with brain metastases. (Baseline imaging required only if clinically indicated).
• Patients with known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
• Patients with hemoptysis within 6 weeks of first dose of study drug.
• Patients who are pregnant or breast feeding.
• Impaired cardiac function including any of the following conditions within the past 6 months:
• NYHA Class II, III or IV heart failure.
• QTc prolongation or other significant ECG abnormalities.
• Myocardial infarction or unstable angina
• Coronary artery bypass graft surgery
• Symptomatic peripheral vascular disease
• History of sustained ventricular tachycardia.
• Patients must not have taken any potent CYP3A4 inhibitors \<= 14 days prior to enrollment including but not limited to:
• ketoconazole, itraconazole, troleandomycin, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, nefazodone, fluvoxamine, diltiazem, verapamil, mibefradil, cimetidine, cyclosporine, and grapefruit juice.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• GlaxoSmithKline: collaborator

Study Sites (4)

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Florida Hospital Cancer Insitute

Orlando, Florida, 32804, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

pazopanib; liposomal doxorubicin

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; Fallopian Tube Diseases

Limitations and Caveats

Per protocol, study did not proceed to phase II based on analyses from phase I. Therefore, Phase II outcomes (all outcomes other than determination of the MTD) were not evaluated and will not be posted.

Results Point of Contact

• Title: John D. Hainsworth, MD
• Organization: Sarah Cannon Research Institute

asksarah@scresearch.net

1-877-691-7274

Study Officials

• T.Michael Numnum, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2009
• First Posted: December 21, 2009
• Study Start: January 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: March 1, 2014
• Last Updated: October 28, 2021
• Results First Posted: May 21, 2015

Record last verified: 2021-10

Locations

US (4)