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

NCT01206140 | Completed Phase 2 Results DMC

• 8 other identifiers: NCI-2011-02532CDR0000685408CHNMC-PHII-95NCCN-T06PHII-958412N01CM00038P30CA033572
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 8

Brief 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. 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.

Conditions

Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (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.

  Until disease progression or death, up to 4.5 years

Secondary Outcomes (2)

• Number of Participants With Objective Response

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

• 4 -Month Progression-free Survival Rate.

  Four months

Study Arms (2)

Arm I (selumetinib and temsirolimus)

EXPERIMENTAL

Patients receive selumetinib PO twice daily on days 1-28 and temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22.

Other: Laboratory Biomarker Analysis; Drug: Selumetinib; Drug: Temsirolimus

Arm II (selumetinib)

EXPERIMENTAL

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

Other: Laboratory Biomarker Analysis; Drug: Selumetinib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (selumetinib and temsirolimus); Arm II (selumetinib)

Selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD6244, MEK Inhibitor AZD6244

Arm I (selumetinib and temsirolimus); Arm II (selumetinib)

Temsirolimus DRUG

Given IV

Also known as: CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel

Arm I (selumetinib and temsirolimus)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• National Comprehensive Cancer Network: collaborator

Study Sites (8)

Tower Cancer Research Foundation

Beverly Hills, California, 90211-1850, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of California Davis Phase 2 Consortium

Sacramento, California, 95817, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

AZD 6244; temsirolimus; Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: DCC Project Administrator
• Organization: California Cancer Consortium

CCCP@coh.org

626-256-4673

Study Officials

• Warren Chow

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2010
• First Posted: September 21, 2010
• Study Start: October 1, 2010
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: October 5, 2015
• Results First Posted: October 5, 2015

Record last verified: 2015-01

Locations

US (8)