NCT00996346

Brief Summary

Refractory soft tissue sarcoma remains a difficult malignancy to treat. The mammalian target of rapamycin (mTOR) is an enzyme that plays an important role in cancer cell survival. mTOR inhibitors, like temsirolimus, have shown activity in sarcoma. Irinotecan is a chemotherapy drug that has also been used to treat sarcoma. However, it is unknown whether combining these two drugs would result in improved efficacy with acceptable toxicity. Therefore, the goal of this phase I study is to determine the maximum tolerated dose (MTD) and toxicity profile of combination temsirolimus and irinotecan both administered intravenously on a weekly basis to refractory soft tissue sarcoma patients.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Oct 2009

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2009

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

October 14, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 16, 2009

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2011

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2013

Completed
1.8 years until next milestone

Results Posted

Study results publicly available

September 1, 2015

Completed
Last Updated

September 1, 2015

Status Verified

August 1, 2015

Enrollment Period

2.1 years

First QC Date

October 14, 2009

Results QC Date

June 6, 2015

Last Update Submit

August 2, 2015

Conditions

Keywords

INST 0909IrinotecanTemsirolimusrefractory sarcomas3066K13066K1-120820091334

Outcome Measures

Primary Outcomes (2)

  • Maximum Tolerated Dose (MTD) of Irinotecan

    The MTD is the dose preceding that at which at least 2 out of 3 patients in the treatment group experience a dose limiting toxicity (DLT). DLT is defined as grade 3 neutropenia on retreatment day, a grade 4 febrile neutropenia, a drug-related grade 3 or 4 non-hematologic toxicity (except fatigue, nausea, vomiting or grade 3 hypersensitivity reaction) or a grade 2 or greater motor or sensory neuropathy

    Up to 1 month

  • Maximum Tolerated Dose (MTD) of Temsirolimus

    The MTD is the dose preceding that at which at least 2 out of 3 patients in the treatment group experience a dose limiting toxicity (DLT). DLT is defined as grade 3 neutropenia on retreatment day, a grade 4 febrile neutropenia, a drug-related grade 3 or 4 non-hematologic toxicity (except fatigue, nausea, vomiting or grade 3 hypersensitivity reaction) or a grade 2 or greater motor or sensory neuropathy

    Up to 1 month

Study Arms (3)

Irinotecan&Temsirolimus:Arm 1, Level 1

EXPERIMENTAL

Arm 1, Level 1: Irinotecan intravenously at 80 mg/m2 + Temsirolimus intravenously at 15 mg on a weekly basis for 3 consecutive doses followed by one week of rest. One cycle is four weeks.

Drug: Irinotecan&Temsirolimus:Arm1, Level 1

Irinotecan&Temsirolimus:Arm 1, Level 2

EXPERIMENTAL

Arm 1, Level 2: Irinotecan intravenously at 80 mg/m2 + Temsirolimus intravenously at 20 mg on a weekly basis for 3 consecutive doses followed by one week of rest. One cycle is four weeks.

Drug: Irinotecan&Temsirolimus:Arm 1, Level 2

Irinotecan&Temsirolimus:Arm 2, Level 1

EXPERIMENTAL

Arm 1, Level 2: Irinotecan intravenously at 50 mg/m2 + Temsirolimus intravenously at 25 mg on a weekly basis for 3 consecutive doses followed by one week of rest. One cycle is four weeks.

Drug: Irinotecan&Temsirolimus:Arm 2, Level 1

Interventions

Irinotecan is given first over 60 minutes followed by temsirolimus over 30 minutes. No intrapatient dose escalations are allowed. Treatment continues until disease progression or intolerable side effects develop.

Also known as: Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
Irinotecan&Temsirolimus:Arm 1, Level 1

Irinotecan is given first over 60 minutes followed by temsirolimus over 30 minutes. No intrapatient dose escalations are allowed. Treatment continues until disease progression or intolerable side effects develop.

Also known as: Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
Irinotecan&Temsirolimus:Arm 1, Level 2

Irinotecan is given first over 60 minutes followed by temsirolimus over 30 minutes. No intrapatient dose escalations are allowed. Treatment continues until disease progression or intolerable side effects develop.

Also known as: Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
Irinotecan&Temsirolimus:Arm 2, Level 1

Eligibility Criteria

Age10 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • All patients, 10 years of age or older with biopsy proven advanced soft tissue sarcoma, who have failed at least one prior treatment for metastatic disease are eligible if there is measurable or evaluable disease per Response Evaluation Criteria In Solid Tumors (RECIST).
  • Patients must have a life expectancy of at least 12 weeks.
  • Prior surgery or radiotherapy for primary tumor is acceptable but must be completed at least 4 weeks from study entry, and patient should have completely recovered from such procedures.
  • Patients must have a Zubrod performance status of 0-2.
  • Patients (or their legal guardian) must sign an informed consent.
  • Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of ≥ 1500 cells/mm3, hemoglobin \> 8 g/dl, platelet count ≥ 100 000/mm3 and absence of a regular red blood cell transfusion requirement.
  • Patients should have a normal hepatic function with a total bilirubin \< the upper limit of normal and Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic pyruvic transaminase (SGPT) \< 2 times the upper limit of normal, and adequate renal function as defined by a serum creatinine ≤ 1.5 upper limit of normal.
  • Fasting total cholesterol level \< 350 mg/dL and triglyceride level \< 400 mg/dL is required.
  • Women of childbearing potential must have a negative pregnancy test.
  • Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and at least for 3 months.
  • Patients with brain metastases are eligible if they have been appropriately treated,are asymptomatic and no longer require corticosteroids.

You may not qualify if:

  • Pregnant women or nursing mothers are not eligible.
  • Patients must not receive any other concurrent chemotherapy or radiation during this trial.
  • Patients with severe medical illnesses such as uncontrolled diabetes, active infections, or uncontrolled psychiatric illnesses are not eligible.
  • Patients with known hypersensitivity to temsirolimus or sirolimus, receiving concomitant antitumor therapy, or anticonvulsant therapy, or cardiac antiarrhythmic drugs are not eligible.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

Related Publications (1)

  • Verschraegen CF, Movva S, Ji Y, Schmit B, Quinn RH, Liem B, Bocklage T, Shaheen M. A phase I study of the combination of temsirolimus with irinotecan for metastatic sarcoma. Cancers (Basel). 2013 Apr 11;5(2):418-29. doi: 10.3390/cancers5020418.

Related Links

MeSH Terms

Conditions

Sarcoma

Interventions

Irinotecantemsirolimus

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasms

Intervention Hierarchy (Ancestors)

CamptothecinAlkaloidsHeterocyclic Compounds

Results Point of Contact

Title
Monte Shaheen, MD / Study Principal Investigator
Organization
University of New Mexico Cancer Center

Study Officials

  • Monte Shaheen, MD

    University of New Mexico Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 14, 2009

First Posted

October 16, 2009

Study Start

October 1, 2009

Primary Completion

November 1, 2011

Study Completion

November 1, 2013

Last Updated

September 1, 2015

Results First Posted

September 1, 2015

Record last verified: 2015-08

Locations