Pazopanib Hydrochloride and Topotecan Hydrochloride in Treating Patients With Metastatic Soft Tissue and Bone Sarcomas

NCT02357810 | Completed Phase 2 Results DMC

• 4 other identifiers: NU 14S03NCI-2014-02583STU00200112P30CA060553
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this clinical research study is to learn if pazopanib when given in combination with topotecan can help to control sarcomas. The safety of this drug combination will also be studied. Pazopanib hydrochloride and topotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Adult Liposarcoma; Metastatic Liposarcoma; Metastatic Osteosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Liposarcoma; Recurrent Osteosarcoma; Stage IV Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival at 12 Weeks for Patients With Soft Tissue Sarcoma (STS) Treated With Pazopanib and Oral Topotecan

  PFS will be defined from the time of enrollment to the study until progression of disease or death from any cause, as assessed by RECIST 1.1 and measured at 12 weeks after treatment initiation for patients with STS. PFS estimates will be calculated using Kaplan-Meier methods Progression is defined as at least a 20% increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Progression must also involve an increase in size of measurable lesions by at least 5 mm, to minimize the possibility that small changes in a small number of target lesions is falsely interpreted as progression.

  At 12 weeks from treatment initiation

Secondary Outcomes (7)

• Overall Response Rate (ORR) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.

  During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33.

• Clinical Benefit Rate (CBR) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.

  During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33.

• Overall Survival (OS) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.

  During treatment where one cycle = 28 days and range of cycles completed by patients 1-33, then for 2 years (for patients with progression) and 5 years (for patients without progression) following discontinuation of treatment

• Number of Patients With Significant Adverse Events, Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03

  From treatment initiation until 30 days post last treatment, at the beginning of each cycle where 1 cycle=28 days. Range of cycles completed by patients 1-33 cycles

• Median Progression Free Survival (PFS) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.

  During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33. And then for up to 5 years post treatment discontinuation.

Other Outcomes (1)

• Change in Cytokine Levels

  Baseline to 12 weeks

Study Arms (1)

Treatment (pazopanib hydrochloride, topotecan hydrochloride)

EXPERIMENTAL

Patients receive pazopanib hydrochloride PO QD on days 1-28 and topotecan hydrochloride PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Pazopanib Hydrochloride; Drug: Oral Topotecan Hydrochloride; Other: Laboratory Biomarker Analysis

Interventions

Pazopanib Hydrochloride DRUG

Given PO

Also known as: GW786034B, Votrient

Treatment (pazopanib hydrochloride, topotecan hydrochloride)

Oral Topotecan Hydrochloride DRUG

Given PO

Also known as: Hycamtin Capsules, Oral Hycamtin

Treatment (pazopanib hydrochloride, topotecan hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pazopanib hydrochloride, topotecan hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Patients must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up
• Patients must have a histologically confirmed diagnosis of:
• Metastatic soft tissue sarcomas (non-liposarcoma)
• Metastatic osteosarcoma
• Metastatic liposarcoma- high grade, de-differentiated, or myxoid Note: pathology is not required to be reviewed at the treating institution; a copy of the pathology report is sufficient for eligibility purposes
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Patients must have measurable disease within 4 weeks prior to registration by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10mm with spiral computed tomography (CT) scan
• Patients must have had a minimum of 1 and a maximum of 4 prior chemotherapy regimens for recurrent/metastatic disease; it will be up to the investigator to determine what constitutes a "regimen" in each case; the last dose of systemic therapy much have been given at least 4 weeks prior to initiation of therapy; patients receiving BCNU or mitomycin C must have received their last dose at least 6 weeks prior to initiation of therapy
• Patients with brain metastasis are eligible for participation only if they have been treated with definitive surgery or radiation (surgery ± radiotherapy, radiosurgery, or gamma knife) and meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 12 week interval
• Absolute neutrophil count (ANC) \>= 1.5 X 10\^9/L (tested within 7 days prior to Registration)
• Hemoglobin \>= 9 g/dL (5.6 mmol/L)
• Subjects may not have had a transfusion within 7 days of screening assessment
• Platelets \>= 100 X 10\^9/L
• Subjects may not have had a transfusion within 7 days of screening assessment
• Prothrombin time (PT) or international normalized ratio (INR) =\< 1.2 X upper limit of normal (ULN)

You may not qualify if:

• Patients with any of the following sarcoma histologic subtypes will not be eligible for participation:
• Alveolar soft-part sarcoma
• Chondrosarcoma
• Dermatofibrosarcoma
• Ewing sarcoma
• Gastrointestinal stromal tumor (GIST)
• Kaposi sarcoma (non-human immunodeficiency virus \[HIV\] and HIV related disease)
• Mixed mesodermal tumor/carcinosarcoma
• Low grade (grade 1) sarcomas
• Rhabdomyosarcoma (embryonal, alveolar, pleomorphic)
• Interdigitating dendritic sarcoma
• Giant cell tumor of the bone
• Patients must not have received prior treatment with pazopanib or topotecan
• Patients must not have an active secondary malignancy
• Prior malignancy, unless they have been disease-free for 3 years, or have a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma

Sponsors & Collaborators

• Northwestern University: lead
• GlaxoSmithKline: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (8)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Northwestern University- Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

  PMID: 31401903 DERIVED

MeSH Terms

Conditions

Liposarcoma; Osteosarcoma; Sarcoma

Interventions

pazopanib; Topotecan

Condition Hierarchy (Ancestors)

Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Mary Mulcahy, MD
• Organization: Northwestern University

Mary.Mulcahy@nm.org

312-695-0990

Study Officials

• Mark Agulnik

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: February 6, 2015
• Study Start: March 21, 2015
• Primary Completion: April 27, 2018
• Study Completion: October 12, 2021
• Last Updated: June 7, 2022
• Results First Posted: August 10, 2020

Record last verified: 2022-05

Locations

US (8)