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Recurrent Adult Soft Tissue SarcomaPhase 2NCT01206140

Selumetinib With or Without Temsirolimus in Treating Patients With Metastatic, Recurrent, or Locally Advanced Soft Tissue Sarcoma That Cannot Be Removed By Surgery

A Phase 2 study testing Laboratory Biomarker Analysis, Selumetinib and Temsirolimus in people with Recurrent Adult Soft Tissue Sarcoma and Stage III Adult Soft Tissue Sarcoma, run by National Cancer Institute (NCI) at 8 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 is studying how well giving selumetinib together with or without temsirolimus works in treating patients with metastatic, recurrent, or locally advanced soft tissue sarcoma that cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Selumetinib and Temsirolimus
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
8 sitesUnited States
Study dates
Oct 2010to Apr 2015
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

  • Patients must have had histologic verification of soft-tissue sarcoma at original diagnosis (GIST subtype is eligible)
  • Patients must have metastatic (de novo or recurrent) or locally advanced, unresectable disease; patients must have measurable disease, 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 >= 10 mm with spiral CT scan
  • ECOG 0-2 (Karnofsky >= 50%)
  • Patients may have received 0-2 prior cytotoxic chemotherapeutic regimens for metastatic or recurrent disease (single-agent or combination chemotherapies)
  • Estimated life expectancy > 12 weeks
  • Peripheral absolute neutrophil count (ANC) >= 1000/uL
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  • Platelet count >= 100,000/uL (transfusion independent)
  • Hemoglobin >= 8.0 gm/dL (may receive RBC transfusions)
  • Creatinine =< 1.5 x upper institutional limits of normal, or calculated creatinine clearance >= 45mL/min, based on the Cockcroft-Gault formula
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
  • SGPT (ALT) =< 5 x upper limit of normal (ULN) for age
  • No evidence of dyspnea at rest, no exercise intolerance
  • Pulse oximetry > 94% if there is clinical indication for determination
  • For women: must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen (for example, intrauterine device [IUD], birth control pills, or barrier device) during and until 4 weeks after the last dose of study treatment; must have a negative serum or urine pregnancy test within 7 days before study enrollment, and must not be breast-feeding; should a woman become pregnant or suspect she is pregnant while she or her partner participating in this study, the patient should inform her treating physician immediately; for men: must be surgically sterile or compliant with a contraceptive regimen during and for 16 weeks after the treatment period; please note that the AZD6244 manufacturer recommends that adequate contraception for male patients should be used for 16 weeks post-last dose due to sperm life cycle
  • All patients must sign a written informed consent

Who cannot join

  • Patients with pediatric-type sarcomas (Ewing's or primitive neuroectodermal tumor, rhabdomyosarcoma, and desmoplastic small round cell tumor)
  • Concomitant Medications
  • Growth factor(s): growth factors that support platelet or white cell number or function must not have been administered within the past 7 days
  • Steroids: patients with CNS tumors who have not been on a stable or decreasing dose of dexamethasone for the past 7 days
  • Investigational Drugs: patients who are currently receiving another investigational drug
  • Anti-cancer Agents: patients who are currently receiving other anti-cancer agents; at least 3 weeks must have elapsed since prior chemotherapy or radiation (6 weeks for mitomycin-C and nitrosureas)
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  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244
  • Previous MEK inhibitor use
  • Patients with QTc interval > 450 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome); this may be determined by either Bazett's correction (QTc =QT/RR0.5) or Friderica's correction (QTc = QT/RR0.33); QTc exclusion > 450 msec requires calculation according to both formulas
  • Patients unable to swallow the AZD6244 capsules are ineligible
  • Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
  • Uncontrolled intercurrent illness including, but not limited to, uncontrolled, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because the effects of AZD6244 on the developing human fetus at the recommended therapeutic dose are unknown; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with AZD6244
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD6244; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study
  • Prior cardiac history of uncontrolled hypertension, New York Heart Association (NYHA) Classification >= class II, current or prior cardiomyopathy, baseline LVEF < 50%, ongoing atrial fibrillation, recent myocardial infarction or unstable ischemic heart disease
  • Concomitant Strong CYP1A2 or CYP3A4 inducers and/or inhibitors; prior treatment with an mTOR inhibitor for recurrent soft-tissue sarcoma

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Tower Cancer Research Foundation

    Beverly Hills, California, 90211-1850

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15232

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • University of California Davis Phase 2 Consortium

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: Randomized, Phase II Trial of AZD6244 Alone and AZD6244 Plus Temsirolimus for Soft-Tissue Sarcomas

This randomized phase II trial is studying how well giving selumetinib together with or without temsirolimus works in treating patients with metastatic, recurrent, or locally advanced soft tissue sarcoma that cannot be removed by surgery. Selumetinib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving selumetinib together with temsirolimus is more effective than giving selumetinib alone.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Compare the progression-free survival of the MEK inhibitor, AZD6244 (selumetinib) alone, and the combination of AZD6244 and a mammalian target of rapamycin inhibitor (mTORi), temsirolimus (CCI-779) in patients with recurrent metastatic or recurrent locally unresectable soft-tissue sarcomas.

SECONDARY OBJECTIVES:

  1. Determine the rates of apoptosis, autophagy, and proliferation with AZD6244 alone, and in combination with temsirolimus by immunohistochemistry in tumor and surrogate skin tissue biopsies. (exploratory) II. Assess the activation status of protein kinase B (Akt), 5E-BP1, eukaryotic translation initiation factor 4 gamma, 1 (eIF-4G), and ribosomal protein S6 kinase (S6K) in tumor biopsy samples and surrogate skin tissue biopsy samples.(exploratory) III. Assess inhibition of activated mitogen-activated protein kinase 1/2 (ERK1/2) in stimulated peripheral blood mononuclear cells. (exploratory) IV. Assess response by Choi criteria. V. Compare the response rate and 4-month progression-free survival (PFS) rate in patients treated with these regimens.

VI. Compare the response rate, 4-month PFS rate and toxicity of AZD6244 alone and in combination with temsirolimus.

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

ARM I: Patients receive selumetinib orally (PO) twice daily on days 1-28 and temsirolimus intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22.

ARM II: Patients receive selumetinib as in arm I. Patients who experience disease progression may cross over to arm I.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for 30 days.

Being tested
Laboratory Biomarker Analysis, Selumetinib, Temsirolimus
Medical subject headings
Sarcoma

What participants receive

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • SelumetinibDrug

    Also called ARRY-142886, AZD6244, MEK Inhibitor AZD6244

    Given PO

  • TemsirolimusDrug

    Also called CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog

    Given IV

Study groups in NCT01206140
Study groupRoleWhat they receive
Arm I (selumetinib and temsirolimus)ExperimentalPatients receive selumetinib PO twice daily on days 1-28 and temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22.
Receives: Other: Laboratory Biomarker Analysis; Drug: Selumetinib; Drug: Temsirolimus
Arm II (selumetinib)ExperimentalPatients receive selumetinib as in arm I. Patients who experience disease progression may cross over to arm I.
Receives: Other: Laboratory Biomarker Analysis; Drug: Selumetinib

What is being measured

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

  1. Progression-free Survival

    Progression-free survival was estimated using the product-limit method of Kaplan and Meier. Progression wasl evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or death.

    Measured: Until disease progression or death, up to 4.5 years

Secondary outcomes (2)

  1. Number of Participants With Objective Response

    Response evaluated using the Choi criteria. CR - disappearance of all lesions and no new lesions; PR - a decrease in size (the sum of longest diameters of target lesions as defined in RECIST) of 10% or more or a decrease in tumor density (HU) of 15% or more on CT and no new lesions and no obvious progression of nonmeasurable disease; SD - does not meet the criteria for CR, PR, or PD and no symptomatic deterioration attributed to tumor progression; PD - an increase in tumor size of 10% or more and does not meet criteria of PR by tumor density (HU) on CT or new lesions or new intratumoral nodules or increase in the size of the existing intratumoral nodules. Objective response = CR+PR.

    Measured: Evaluated for response after every two cycles, up to 4.5 years.

  2. 4 -Month Progression-free Survival Rate.

    Progression-free survival rate was calculated using the survival distribution function, and 95% confidence limits were calculated using the log-log transformation. Progression was defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or death.

    Measured: Four months

Timeline

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

  1. First posted21 Sep 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionApr 2015
  4. Study completionApr 2015

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
Parallel groups
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01206140
Sponsor's protocol ID
NCI-2011-02532
Other IDs
NCI-2011-02532, CDR0000685408, CHNMC-PHII-95, NCCN-T06, PHII-95, 8412, N01CM00038, P30CA033572
Status last verified
Jan 2015
First submitted
18 Sep 2010
Last updated
5 Oct 2015
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Selumetinib and Temsirolimus in people with Recurrent Adult Soft Tissue Sarcoma and Stage III Adult Soft Tissue Sarcoma, run by National Cancer Institute (NCI) at 8 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 15 inclusion and 18 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 5 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 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 5 Oct 2015). 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 (time frame: Until disease progression or death, up to 4.5 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 NCT01206140.

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 5 Oct 2015.

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