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

NCT01048723 | Terminated Phase 2 Results DMC

• 3 other identifiers: MCC-15962CRAD001CUS107T108182
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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 safe and effective in patients with this condition. The study drug, RAD001, is made by Novartis Pharmaceuticals Corporation.

Conditions

Sarcoma

Keywords

Soft Tissue; Retroperitoneal; resectable

Outcome Measures

Primary Outcomes (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.

  Pre and post the 2 week treatment

Secondary Outcomes (3)

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

  Post the 2 week treatment

• Number of Participants With Pathological Response

  Post the 2 week treatment

• Number of Participants With Memory CD8 T Cell Enhanced Production

  Pre and Post the 2 week treatment

Study Arms (1)

RAD001 Administration

EXPERIMENTAL

RAD001 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.

Drug: RAD001

Interventions

RAD001 DRUG

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

Also known as: everolimus

RAD001 Administration

Eligibility Criteria

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

You may qualify if:

• 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.)
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Novartis: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

This study was terminated early due to sponsor budget cuts. We could not meet our accrual goal to perform planned analysis of 40 participants.

Results Point of Contact

• Title: Jonathan Zager, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

jonathan.zager@moffitt.org

813-745-1085

Study Officials

• Jonathan S. Zager, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2010
• First Posted: January 14, 2010
• Study Start: January 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: December 16, 2013
• Results First Posted: August 17, 2012

Record last verified: 2012-07

Locations

US (1)