A Treatment Trial Comparing Gemcitabine and Pazopanib Versus Gemcitabine and Docetaxel for Patients With Advanced Soft Tissue Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Medical University of South Carolina
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Andrew S. Kraft, MD, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT01593748
First received: May 4, 2012
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

This study is for adult subjects with advanced tissue sarcoma. The study involves the drugs Pazopanib (Votrient), Gemcitabine (Gemzar), and Docetaxel (Taxotere). The purpose of this study is to test the effectiveness and safety of Gemcitabine and Pazopanib compared with Gemcitabine and Docetaxel in participants with soft tissue sarcoma.


Condition Intervention Phase
Sarcoma
Drug: Gemcitabine and Pazopanib
Drug: Gemcitabine and Docetaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Phase II, Multi-center Trial of Gemcitabine (G) With Pazopanib (P) or Gemcitabine (G) With Docetaxel (T) in Previously Treated Subjects With Advanced Soft Tissue Sarcoma

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To estimate the progression-free survival (PFS) of the combination of gemcitabine plus pazopanib (G+P) and to estimate the PFS of the combination of gemcitabine plus docetaxel (G+T) in patients with previously treated, metastatic and/or locally advanced or recurrent soft tissue sarcoma. To estimate the rate of grade 3 or higher toxicity with G+P and G+T and to describe the type and grade of toxicities.


Secondary Outcome Measures:
  • Hazard ratio [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    To estimate the hazard ratio comparing G+P vs. G+T in patients with previously treated, metastatic and/or locally advanced or recurrent soft tissue sarcoma. To estimate the response rates of G+P and G+T in metastatic and/or locally advanced or recurrent soft tissue sarcoma patients. To examine quality of life (QOL) measures with both regimens (using EORTC QLQ-C30 version 3 and EuroQol questionnaires).


Estimated Enrollment: 90
Study Start Date: May 2012
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Patients in Group 1 will get Gemcitabine 1000 mg/m2 intravenously on Day 1 and Day 8 and Pazopanib 800mg by mouth daily on a 21 day cycle. Cycles will continue until disease progression or patient withdrawal.
Drug: Gemcitabine and Pazopanib
Gemcitabine 1000mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Pazopanib 800mg tablet daily for a 21 day cycle.
Active Comparator: Group 2
Patients in Group 2 will get Gemcitabine 900 mg/m2 intravenously on Day 1 and Day 8. Additionally on Day 8, patients will have Docetaxel 100 mg/m2 given intravenously. on a 21 day cycle. If disease progression occurs on this treatment, patients will have the option to receive treatment with Gemcitabine and Pazopanib (group 1).
Drug: Gemcitabine and Docetaxel
Gemcitabine 900 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Docetaxel 100mg/m2 by IV on day 8 of a 21 day cycle.

Detailed Description:

The purpose of this study is to test the effectiveness and safety of Gemcitabine and Pazopanib compared with Gemcitabine and Docetaxel in participants with soft tissue sarcoma. Screening tests will be done to ensure subjects are eligible to participate in this study. If the exams, tests and procedures show that subjects can be in the study, and they choose to take part, then they will be "randomized" into one of the two study groups: Group 1 or Group 2. Subjects in Group 1 will receive Gemcitabine 1000 mg/m2 intravenously (directly into a vein) on Day 1 and Day 8 and Pazopanib 800mg by mouth daily. Subjects in Group 2 will receive Gemcitabine 900 mg/m2 intravenously on Day 1 and Day 8 and Docetaxel 100 mg/m2 intravenously on Day 8. Both groups will be in 21 day cycles. Both groups will be asked to complete "quality of life" questionnaires, on their first visit, then at 6 weeks (2nd cycle), 18 weeks (6th cycle) and at the end of study treatment. Subjects will be followed for up to 2 years.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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.
  • Age ≥ 18 years or legal age of consent if greater than 18 years.
  • Histologically or cytologically confirmed diagnosis of sarcoma of soft tissue. (Patients with liposarcoma, bone sarcoma or GIST will be excluded).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Subjects must have metastatic and/or locally advanced or locally recurrent disease that is not amenable to curative surgical resection.
  • A minimum of 1 and a maximum of 3 prior chemotherapy regimens for recurrent/metastatic disease. Patients eligible for an anthracycline should have received a prior anthracycline containing regimen. Patients who decline or are not eligible for anthracycline treatment may be considered for this protocol as a first line treatment.
  • Patients must have measurable disease by RECIST 1.1. or cutaneous disease amenable to serial measurements should be present. Measurable disease (a 'target' lesion) is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT (CT scan slice thickness no greater than 5 mm); ≥ 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as non-measurable); and ≥ 20 mm by chest x-ray.
  • Able to swallow and retain oral medication.
  • Adequate organ system function
  • A female is eligible to enter and participate in this study if she is of:

    • Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had:

      • A hysterectomy
      • A bilateral oophorectomy (ovariectomy)
      • A bilateral tubal ligation
      • Is post-menopausal

Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥ 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value < 40pg/mL (< 140 pmol/L).

Subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT.

-- Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:

  • Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product
  • Oral contraceptive, either combined or progestogen alone
  • Injectable progestogen
  • Implants of levonorgestrel
  • Estrogenic vaginal ring
  • Percutaneous contraceptive patches
  • Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year
  • Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject
  • Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)

Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.

Exclusion Criteria

  • Prior therapy with pazopanib, gemcitabine or docetaxel.
  • Any concern for hypersensitivity to pazopanib, gemcitabine or docetaxel.
  • 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 or successfully treated in situ carcinoma 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 and experiencing the "dumping" syndrome.

    • Presence of uncontrolled infection.
    • Prior mediastinal radiation
    • Corrected QT interval (QTc) > 480 msecs using Bazett's formula.
    • History of any one or more of the following conditions within the past 6 months:
  • Cardiac angioplasty or stenting
  • Myocardial infarction
  • Unstable angina
  • Coronary artery bypass graft surgery
  • Symptomatic peripheral vascular disease
  • Pneumonitis

    • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) (Appendix D).
    • Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥ 150 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 < 150/90 mmHg in order for a subject to be eligible for the study.

-History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.

  • Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
  • Evidence of active bleeding or bleeding diathesis.
  • Known endobronchial lesions and/or lesions infiltrating major pulmonary Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug.
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  • Unable or unwilling to discontinue use of prohibited medications listed in Section 5.2.3 for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
  • Treatment with any of the following anti-cancer or non-oncologic investigational therapies:

    • radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of study drug
    • chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or 2.5 half-lives of a drug (whichever is longer) prior to the first dose of study drug.
    • non-oncologic investigational products within 30 days or 5 halflives, whichever is longer.
  • Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01593748

Contacts
Contact: Tricia Bentz, MHA 843-792-1753 adraleta@musc.edu

Locations
United States, California
Sarcoma Oncology Center Recruiting
Santa Monica, California, United States, 90403
Principal Investigator: Sant P Chawla, MD         
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Anthony Elias, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: William Read, MD         
United States, Iowa
University of Iowa Hospitals & Clinics Recruiting
Iowa City, Iowa, United States
Principal Investigator: Mohammed Milhem, M.B., B.S.         
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Edward A. Sausville, M.D., Ph.D.         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Principal Investigator: Scott M Schuetze, MD, PhD         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Neeta Somaiah, MD         
Sponsors and Collaborators
Medical University of South Carolina
GlaxoSmithKline
Investigators
Principal Investigator: Andrew Kraft, MD Medical University of South Carolina Hollings Cancer Center
  More Information

Publications:
Responsible Party: Andrew S. Kraft, MD, Director, Hollings Cancer Center, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT01593748     History of Changes
Other Study ID Numbers: MUSC 101644, PAZ115785
Study First Received: May 4, 2012
Last Updated: July 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Medical University of South Carolina:
Sarcoma
Soft Tissue Sarcoma

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Docetaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 30, 2014