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SarcomaPhase 2NCT01048723

Study of RAD001 in Soft Tissue Extremity and/or Retroperitoneal Sarcomas

A Phase 2 study testing RAD001 in people with Sarcoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The goal of this clinical research study is to learn if the study drug RAD001 can stop or slow the growth of resectable soft tissue sarcoma. The patient's physical state, their symptoms, changes in the size of the tumor, and laboratory findings obtained while on-study will help the research team decide if RAD001 is… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sarcoma
What is being tested?
RAD001
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
Jan 2010to Oct 2011
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

  • Have a resectable primary or recurrent sarcoma according to diagnostic imaging criteria (computed tomography [CT] and/or magnetic resonance imaging [MRI]) that has not been previously irradiated.
  • Primary/recurrent or persistent sarcoma must be amenable to core biopsy for pre RAD001 pharmacodynamic studies
  • World Health Organization (WHO) performance status ≤ 2
  • Adequate bone marrow function shown by: absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, Platelets ≥ 100 x 10^9/L, hemoglobin (Hb) >9 g/dL
  • Adequate liver function shown by: serum bilirubin ≤ 1.5 x upper limit of normal (ULN); alanine transaminase (ALT) and aspartic transaminase (AST) ≤ 2.5x ULN
  • International Normal Ratio (INR) and partial thromboplastin time (PTT) ≤1.5. (Anticoagulation allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for > 2 weeks at time of randomization.)
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  • Adequate renal function: serum creatinine ≤ 1.5 x ULN
  • Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, patient can only be included after initiation of appropriate lipid lowering medication.
  • Signed informed consent
  • Patients with resectable soft tissue extremity or retroperitoneal sarcomas amenable to pre-treatment core biopsy
  • Biopsy proven surgically resectable retroperitoneal sarcomas of any histologic grade

Who cannot join

  • Currently receiving anticancer therapies or have received anticancer therapies within 4 weeks of the start of study drug. Note: Primary/recurrent/ persistent sarcoma must not have been previously treated with radiation. Primary/recurrent or persistent sarcoma must not have been treated within 4 weeks of the start of RAD001 with other chemotherapeutic agents
  • Have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
  • Receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
  • Should not receive immunization with attenuated live vaccines within 1 week of study entry or during study period
  • Brain or leptomeningeal metastases
  • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
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  • Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: Symptomatic congestive heart failure of New York Heart Association (NYHA) Class III or IV; unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease; severely impaired lung function as defined as spirometry and diffusing lung capacity oxygenation (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air; uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN; active (acute or chronic) or uncontrolled severe infections; liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  • Known history of human immunodeficiency virus (HIV) seropositivity
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
  • Patients with an active, bleeding diathesis
  • Females who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001)
  • Received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
  • Known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients
  • History of noncompliance to medical regimens
  • Unwilling or unable to comply with the protocol
  • Cutaneous sarcomas or sarcomas where neoadjuvant chemotherapy or radiation may be indicated in the treatment plan
  • Sarcomas must be deemed fully resectable by pre-treatment imaging
  • No evidence of distant disease

Trial locations and contacts

1 site in 1 country.

United States1 site

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Single-arm, Open Label Phase II Study of RAD001 in Soft Tissue Extremity and/or Retroperitoneal Sarcomas

The goal of this clinical research study is to learn if the study drug RAD001 can stop or slow the growth of resectable soft tissue sarcoma. The patient's physical state, their symptoms, changes in the size of the tumor, and laboratory findings obtained while on-study will help the research team decide if RAD001 is safe and effective in patients with this condition. The study drug, RAD001, is made by Novartis Pharmaceuticals Corporation.

Read the detailed description

A single-arm, open label, proof of principle phase II study exploring the efficacy of RAD001 in resectable soft tissue sarcomas either in the extremities, trunk or retroperitoneum. Patients with resectable sarcomas as detailed below were to have a core biopsy for molecular markers prior to therapy with RAD001 10mg PO daily x 2 weeks. Within 7-14 days of the end of therapy with RAD001, the patients were to be brought to surgery for definitive resection or, should they be candidates for neoadjuvant radiation, would have 6 16 gauge core biopsies taken percutaneously or using image guidance. Pharmacodynamic markers as detailed in the objectives were to be assessed in the laboratory.

Patients were to be numbered sequentially from 1 to 40, or more if there were patients that dropped out due to drug toxicity, with the goal of achieving 40 patients in accrual for evaluation of the pre- and post-treatment tumor samples for Pharmacodynamic assays.

Conditions
Sarcoma
Being tested
RAD001
Keywords
Soft Tissue, Retroperitoneal, resectable
Medical subject headings
Sarcoma

What participants receive

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

  • RAD001Drug

    Also called everolimus

    Patients were instructed to take RAD001 in the morning, at the same time each day.

Study groups in NCT01048723
Study groupRoleWhat they receive
RAD001 AdministrationExperimentalRAD001 was administered orally as once daily dose of 10 mg PO daily x 2 weeks (14 X 10 mg tablets) continuously from study day 1 until the end of therapy (2 weeks later) or unacceptable toxicity.
Receives: Drug: RAD001

What is being measured

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

  1. Pharmacodynamics (PD) Markers

    PD markers of RAD001 on downstream signaling pathways in patients with sarcomas: p70S6K, S6-RP, P-AKT, cleaved PARP and PCNA by Western blot, quantitative multiplex assays and immunohistochemical studies measured pre and post the 2 week treatment of RAD001. Patients were to be separated into two groups, responders and non responders based on PD results and downstream up regulation of the referenced pathways. Mean fractional inhibition of each PD marker for the responding and non-responding groups were to be calculated. Our planned analysis was for 40 participants.

    Measured: Pre and post the 2 week treatment

Secondary outcomes (3)

  1. PD Markers (p70S6K, S6-RP, P-AKT, Cleaved PARP and PCNA)

    Quantitative in vivo and ex vivo assessments of PD markers (p70S6K, S6-RP, P-AKT, cleaved PARP and PCNA) were to be normalized within the same sample. The extent of inhibition is defined as the fractional inhibition in each patient calculated as [(PreRx normalized PD marker - PostRx normalized PD marker) / PreRx normalized PD marker] x 100. Same definition would apply to each of these markers. Our planned analysis was for 40 participants.

    Measured: Post the 2 week treatment

  2. Number of Participants With Pathological Response

    We planned to determine pathological response in terms of tumor necrosis and apoptosis assessed on the resected specimens after 2 weeks of RAD001 therapy. Percent necrosis was to be reported based on the routine H and E staining. In addition to cleaved PARP analysis, TUNEL assays were to be performed judging the amount of apoptosis in the specimens after treatment. Our planned analysis was for 40 participants.

    Measured: Post the 2 week treatment

  3. Number of Participants With Memory CD8 T Cell Enhanced Production

    Memory CD8 T cell enhanced production as determined by fluorescence activated cell sorter (FACS) analysis on blood and tumor core biopsy specimens taken before and after therapy with RAD001. Our planned analysis was for 40 participants.

    Measured: Pre and Post the 2 week treatment

Timeline

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

  1. First posted14 Jan 2010 (estimated)
  2. Study startJan 2010
  3. Primary completionOct 2011
  4. Study completionOct 2011

Why it stopped: Novartis terminated funding

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01048723
Sponsor's protocol ID
MCC-15962
Other IDs
CRAD001CUS107T, 108182
Status last verified
Jul 2012
First submitted
13 Jan 2010
Last updated
16 Dec 2013
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RAD001 in people with Sarcoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site 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 11 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: stopped early, as of the sponsor's last update on 16 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 17 Aug 2012). 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?

Pharmacodynamics (PD) Markers (time frame: Pre and post the 2 week treatment). 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 NCT01048723.

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 16 Dec 2013.

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