Gemcitabine With or Without Pazopanib in Treating Patients With Refractory Soft Tissue Sarcoma

NCT01532687 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB00007943NCI-2012-00052
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

This randomized phase II trial studies how well gemcitabine hydrochloride works with or without pazopanib hydrochloride in treating patients with refractory soft tissue sarcoma. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pazopanib hydrochloride may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether gemcitabine hydrochloride is more effective with or without pazopanib hydrochloride in treating patients with soft tissue sarcoma.

Conditions

Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated Pleomorphic Sarcoma; Malignant Adult Hemangiopericytoma; Recurrent Adult Soft Tissue Sarcoma; Sarcoma; Stage III Adult Soft Tissue Sarcoma AJCC v7; Stage IV Adult Soft Tissue Sarcoma AJCC v7

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Compared using a one-sided Gehan-Wilcoxon test stratified by sarcoma subtype. Kaplan-Meier estimates for each treatment arm will be presented with the estimated hazard ratios and their associated confidence intervals. Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 as at least a 20% increase in the sum of the longest diameters of target lesions (taking as reference the smallest sum on study) with an absolute increase of at least 5 mm (target lesions), or measurable increase in non-target lesions (unequivocal progression), or appearance of one or more new lesions.

  Calculated as the time from randomization to the first documented progression or death, whichever occurs first, or until time of last contact if no progression or death occurred, assessed up to 3 years

Secondary Outcomes (3)

• Progression-free Survival (PFS) for a Sub-group of Patients Treated With Open-label Pazopanib Hydrochloride Following Administration of Gemcitabine Hydrochloride in the Cross-over Portion of This Study

  Calculated as the time from receiving open-labeled pazopanib hydrochloride to the next documented progression or death whichever occurs first, assessed up to 3 years

• Percentage of Participants Achieving Best Overall Objective Response (CR+PR)

  Best overall objective response recorded from the start of treatment until disease progression/recurrence assessed up to 3 years

• Overall Survival

  From randomization to death due to any cause, or until last patient contact if the patient did not die, assessed up to 3 years

Study Arms (2)

Arm I (gemcitabine hydrochloride and pazopanib hydrochloride)

EXPERIMENTAL

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Pazopanib; Drug: Pazopanib Hydrochloride

Arm II (gemcitabine hydrochloride, placebo)

ACTIVE COMPARATOR

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Pazopanib; Drug: Pazopanib Hydrochloride; Other: Placebo Administration

Interventions

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Arm I (gemcitabine hydrochloride and pazopanib hydrochloride); Arm II (gemcitabine hydrochloride, placebo)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011

Arm I (gemcitabine hydrochloride and pazopanib hydrochloride); Arm II (gemcitabine hydrochloride, placebo)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (gemcitabine hydrochloride and pazopanib hydrochloride); Arm II (gemcitabine hydrochloride, placebo)

Pazopanib DRUG

Given PO

Also known as: GW786034

Arm I (gemcitabine hydrochloride and pazopanib hydrochloride); Arm II (gemcitabine hydrochloride, placebo)

Pazopanib Hydrochloride DRUG

Given PO

Also known as: GW786034B, Votrient

Arm I (gemcitabine hydrochloride and pazopanib hydrochloride); Arm II (gemcitabine hydrochloride, placebo)

Placebo Administration OTHER

Given PO

Arm II (gemcitabine hydrochloride, placebo)

Eligibility Criteria

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

You may qualify if:

• Subjects 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; procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol
• Histologically confirmed diagnosis of metastatic or unresectable soft tissue sarcoma, excluding gastrointestinal stromal tumors, Kaposi's sarcoma, Ewing's family of tumors, and embryonal or alveolar rhabdomyosarcoma
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Patients must have received at least one, but not more than three, systemic regimens for treatment of metastatic soft tissue sarcoma; patients must have had a prior anthracycline in the neoadjuvant, adjuvant, or metastatic setting unless medically inappropriate for the patient
• Neoadjuvant or adjuvant therapy will not count towards prior treatment for metastatic disease, unless the patient relapsed within 2 years of completing such therapy.
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Hemoglobin \>= 8 g/dL; subjects may not have had a transfusion within 7 days of screening assessment
• Platelets \>= 100 x 10\^9/L
• Prothrombin time (PT) or international normalized ratio (INR) =\< 1.2 x upper limit of normal (ULN); subjects receiving anticoagulation therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation
• Activated partial thromboplastin time (aPTT) =\< 1.2 x ULN
• Total bilirubin =\< 1.5 x ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN; concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN (upper limit of normal) are not permitted
• Serum creatinine =\< 1.5 mg/dL (133 umol/L)
• Or, if \> 1.5 mg/dL: calculated creatinine clearance (ClCR) \>= 30 mL/min

You may not qualify if:

• Prior malignancy; note: subjects who have had another malignancy and have been disease-free for \> 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma, successfully treated in situ carcinoma, or successfully treated superficial bladder cancer 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 may increase the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• Known intraluminal metastatic lesion/s with risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
• Malabsorption syndrome
• Major resection of the stomach or small bowel
• Presence of uncontrolled infection
• Corrected QT interval (QTc) \> 480 msecs 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Novartis Pharmaceuticals: collaborator
• Oregon Health and Science University: collaborator

Study Sites (2)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, 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

Sarcoma, Alveolar Soft Part; Hemangiosarcoma; Desmoplastic Small Round Cell Tumor; Hemangioendothelioma, Epithelioid; Sarcoma; Chondrosarcoma, Extraskeletal Myxoid; Fibrosarcoma; Leiomyosarcoma; Liposarcoma; Neurofibrosarcoma; Rhabdomyosarcoma; Sarcoma, Synovial; Histiocytoma, Malignant Fibrous

Interventions

Gemcitabine; pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Hemangioendothelioma; Hemangioma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Adipose Tissue; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Myosarcoma; Histiocytoma

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Christopher Ryan
• Organization: OHSU Knight Cancer Institute

ryanc@ohsu.edu

503-494-9000

Study Officials

• Christopher W Ryan

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 6, 2012
• First Posted: February 14, 2012
• Study Start: March 13, 2012
• Primary Completion: October 31, 2019
• Study Completion: October 31, 2019
• Last Updated: September 27, 2021
• Results First Posted: February 9, 2021

Record last verified: 2021-09

Locations

US (2)