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Adult Alveolar Soft Part SarcomaPhase 2NCT01532687

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

A Phase 2 study testing Gemcitabine, Gemcitabine Hydrochloride and Laboratory Biomarker Analysis in people with Adult Alveolar Soft Part Sarcoma and Adult Angiosarcoma, run by OHSU Knight Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gemcitabine, Gemcitabine Hydrochloride and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
54 participants
Where
2 sitesUnited States
Study dates
13 Mar 2012to 31 Oct 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Urine protein to creatinine ratio (UPC) < 1; if UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable
  • Or 24-hour urine protein < 1 g
  • 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 < 40 pg/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 7 days prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception; defined as follows:
  • 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 progesterone alone
  • Injectable progesterone
  • 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

Who cannot join

  • 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
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  • 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
  • Unstable angina
  • Coronary artery bypass graft surgery
  • Symptomatic peripheral vascular disease
  • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
  • 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; following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals; at least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement; these three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure; the mean SBP/DBP ratio must be < 140/90 mmHg
  • 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 vessels that increase the risk of pulmonary hemorrhage
  • 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 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; administration of any non-oncologic investigational drug within 30 days or 5 half-lives whichever is longer prior to receiving the first dose of study treatment
  • Treatment with any of the following anti-cancer therapies:
  • Radiation therapy, 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 28 days in the case of monoclonal antibody therapy) prior to the first dose of pazopanib.
  • Any prior treatment with pazopanib.
  • Prior treatment with vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR)-targeting agents other than pazopanib (eg. sorafenib, sunitinib, and bevacizumab) in the metastatic setting. Prior use of such agents in the neoadjuvant or adjuvant setting is permitted.
  • Any prior treatment with gemcitabine for metastatic disease. Prior use of gemcitabine in the neoadjuvant or adjuvant setting is permitted.
  • Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity, except alopecia

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Randomized, Double-Blind Phase II, Study of Gemcitabine Alone or in Combination With Pazopanib for Refractory Soft Tissue Sarcoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To investigate whether treatment with gemcitabine (gemcitabine hydrochloride) plus pazopanib (pazopanib hydrochloride) improves the median progression-free survival (PFS) of patients with metastatic soft tissue sarcoma when compared to gemcitabine plus placebo.

SECONDARY OBJECTIVES:

  1. To assess overall response in this population to gemcitabine plus pazopanib compared to gemcitabine plus placebo.

II. To assess overall survival (OS) in this population to gemcitabine plus pazopanib compared to gemcitabine plus placebo.

III. To investigate differences in treatment response in different histologic subgroups (liposarcoma vs. all other eligible soft tissue sarcoma subtypes).

IV. To evaluate the safety and tolerability of the combination of gemcitabine plus pazopanib.

  1. To assess the progression-free survival and overall response in patients treated with single agent pazopanib following administration of gemcitabine in the cross-over portion of this study.

VI. To collect specimens for an exploratory analysis of potential biomarkers that predict response in patients receiving combination therapy with gemcitabine plus pazopanib.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

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

ARM II: 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.

After the completion of study treatment, patients are followed up every 3 months.

Being tested
Gemcitabine, Gemcitabine Hydrochloride, Laboratory Biomarker Analysis, Pazopanib, Pazopanib Hydrochloride
Medical subject headings
Sarcoma, Alveolar Soft Part, Hemangiosarcoma, Desmoplastic Small Round Cell Tumor, Hemangioendothelioma, Epithelioid, Sarcoma, Chondrosarcoma, Extraskeletal Myxoid, Fibrosarcoma, Leiomyosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GemcitabineDrug

    Also called dFdC, dFdCyd, Difluorodeoxycytidine

    Given IV

  • Gemcitabine HydrochlorideDrug

    Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PazopanibDrug

    Also called GW786034

    Given PO

  • Pazopanib HydrochlorideDrug

    Also called GW786034B, Votrient

    Given PO

  • Placebo AdministrationOther

    Given PO

Study groups in NCT01532687
Study groupRoleWhat they receive
Arm I (gemcitabine hydrochloride and pazopanib hydrochloride)ExperimentalPatients 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.
Receives: Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Pazopanib; Drug: Pazopanib Hydrochloride
Arm II (gemcitabine hydrochloride, placebo)Active comparatorPatients 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.
Receives: Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Pazopanib; Drug: Pazopanib Hydrochloride; Other: Placebo Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. 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

    Participants who progress during treatment and are found to be part of the gemcitabine+placebo arm after unblinding are eligible to receive open-label pazopanib with gemcitabine. This is the crossover population. Statistical analysis is exploratory and requires sufficient crossover participants to assess Kaplan-Meier estimated hazard ratio and associated 95% confidence interval. This represents the participants second progression. In both cases 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 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. First progression uses the smallest sum on study as a reference; progression for the crossover population uses first progression measurements as the reference.

    Measured: 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

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

    Response is evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where RECIST combines assessments for target, non-target and presence of new lesions. Best Overall Objective Response is the sum of all CR+PR divided by all randomized participants, where the strongest recorded response is used for the evaluation (CR>PR>SD>PD). Objective response (CR+PR) requires at least a 30% decrease in the sum of the largest diameter target lesions (with respective to the baseline sum); disappearance of all or persistence of one or more non-target lesions, maintenance of tumor marker levels above normal limits, and no new lesions. Estimated odds ratio of best overall objective response are reported with 95% confidence interval for the two histologic sarcoma subgroups (liposarcoma vs all other eligible soft tissue sarcoma subtypes). One-sided proportions test is used to determine whether best overall objective response is greater for the gemcitabine plus pazopanib group.

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

  3. Overall Survival

    Two treatment arms will be compared using a one-sided log-rank test stratified by sarcoma subtype and study site. Kaplan-Meier estimates and the survival curves for each treatment arm will be presented with the estimated hazard ratios and their associated confidence interval.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Feb 2012 (estimated)
  2. Study start13 Mar 2012
  3. Primary completion31 Oct 2019
  4. Study completion31 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01532687
Sponsor's protocol ID
IRB00007943
Other IDs
NCI-2012-00052, IRB00007943
Status last verified
Sep 2021
First submitted
6 Feb 2012
Last updated
27 Sep 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 31401903

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gemcitabine, Gemcitabine Hydrochloride and Laboratory Biomarker Analysis in people with Adult Alveolar Soft Part Sarcoma and Adult Angiosarcoma, run by OHSU Knight Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01532687, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2021.

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