SarcomaPhase 1NCT00996346
Phase I/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas
A Phase 1 study testing Irinotecan&Temsirolimus:Arm1, Level 1, Irinotecan&Temsirolimus:Arm 1, Level 2 and Irinotecan&Temsirolimus:Arm 2, Level 1 in people with Sarcoma, run by New Mexico Cancer Research Alliance at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Sarcoma
- What is being tested?
- Irinotecan&Temsirolimus:Arm1, Level 1, Irinotecan&Temsirolimus:Arm 1, Level 2 and Irinotecan&Temsirolimus:Arm 2, Level 1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Nov 2013
- Phase
- Phase 1
- 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 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
About this study
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.
Read the detailed description
Mammalian target of rapamycin (mTOR) inhibitors are anti-neoplastic agents with a wide potential range of clinical applications. The topoisomerase I inhibitor irinotecan is a potent DNA damaging drug. mTOR appears to enhance cancer cell survival following DNA damage, so it's reasonable to expect that mTOR inhibition combined with irinotecan may result in synergistic activity.
This is a single arm, non-randomized phase I trial of temsirolimus (an mTOR inhibitor) and irinotecan (a topoisomerase I inhibitor) in refractory soft tissue sarcoma patients. Successive groups of three patients will be entered at escalating dose levels. Irinotecan and temsirolimus will be administered weekly for three weeks followed by one week of rest. One course will therefore be four weeks. No intra-patient dose escalation will be allowed. Each patient will be treated until disease progression or intolerable side effects develop. Dose limiting toxicities will be assessed and the maximum tolerated dose will be reported.
Note that this trial was originally designed as a phase I/II study, but only the phase I portion was completed and will be reported.
- Conditions
- Sarcoma
- Being tested
- Irinotecan&Temsirolimus:Arm1, Level 1, Irinotecan&Temsirolimus:Arm 1, Level 2, Irinotecan&Temsirolimus:Arm 2, Level 1
- Keywords
- INST 0909, Irinotecan, Temsirolimus, refractory sarcomas, 3066K1, 3066K1-1208, 20091334
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irinotecan&Temsirolimus:Arm1, Level 1Drug
Also called Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
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.
Irinotecan&Temsirolimus:Arm 1, Level 2Drug
Also called Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
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.
Irinotecan&Temsirolimus:Arm 2, Level 1Drug
Also called Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Irinotecan&Temsirolimus:Arm 2, Level 1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Up to 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionNov 2011
- Study completionNov 2013
Why it stopped: Original PI left institution and sponsor decided to end support.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- New Mexico Cancer Research Alliance
- Sponsor type
- University, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Responsible party
- Sponsor
- Investigators
- Monte Shaheen, MD, Principal investigator, University of New Mexico Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00996346
- Sponsor's protocol ID
- INST 0909
- Other IDs
- 3066K1, 3066K1-1208, 20091334, NCI-2011-01940
- Status last verified
- Aug 2015
- First submitted
- 14 Oct 2009
- Last updated
- 1 Sep 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24216984
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas
- ClinicalTrials.gov ID
- NCT00996346
- Acronym / sponsor ID
- INST 0909
- Conditions
- Sarcoma
- Keywords
- INST 0909, Irinotecan, Temsirolimus, refractory sarcomas, 3066K1, 3066K1-1208, 20091334
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Original PI left institution and sponsor decided to end support.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- New Mexico Cancer Research AllianceUniversity, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Study start
- Oct 2009
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 16 Oct 2009 (estimated)
- Results
- Posted 1 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Mammalian target of rapamycin (mTOR) inhibitors are anti-neoplastic agents with a wide potential range of clinical applications. The topoisomerase I inhibitor irinotecan is a potent DNA damaging drug. mTOR appears to enhance cancer cell survival following DNA damage, so it's reasonable to expect that mTOR inhibition combined with irinotecan may result in synergistic activity.
This is a single arm, non-randomized phase I trial of temsirolimus (an mTOR inhibitor) and irinotecan (a topoisomerase I inhibitor) in refractory soft tissue sarcoma patients. Successive groups of three patients will be entered at escalating dose levels. Irinotecan and temsirolimus will be administered weekly for three weeks followed by one week of rest. One course will therefore be four weeks. No intra-patient dose escalation will be allowed. Each patient will be treated until disease progression or intolerable side effects develop. Dose limiting toxicities will be assessed and the maximum tolerated dose will be reported.
Note that this trial was originally designed as a phase I/II study, but only the phase I portion was completed and will be reported.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Irinotecan&Temsirolimus:Arm 1, Level 1 | Experimental | Drug: Irinotecan&Temsirolimus:Arm1, Level 1Arm 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. |
| Irinotecan&Temsirolimus:Arm 1, Level 2 | Experimental | Drug: Irinotecan&Temsirolimus:Arm 1, Level 2Arm 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. |
| Irinotecan&Temsirolimus:Arm 2, Level 1 | Experimental | Drug: Irinotecan&Temsirolimus:Arm 2, Level 1Arm 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. |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Irinotecan&Temsirolimus:Arm1, Level 1Also: Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779Irinotecan 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. | Drug | Irinotecan&Temsirolimus:Arm 1, Level 1 |
| Irinotecan&Temsirolimus:Arm 1, Level 2Also: Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779Irinotecan 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. | Drug | Irinotecan&Temsirolimus:Arm 1, Level 2 |
| Irinotecan&Temsirolimus:Arm 2, Level 1Also: Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779Irinotecan 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. | Drug | Irinotecan&Temsirolimus:Arm 2, Level 1 |
Primary outcome
Maximum Tolerated Dose (MTD) of Irinotecan
Time frame: Up to 1 month
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
Maximum Tolerated Dose (MTD) of Temsirolimus
Time frame: Up to 1 month
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24216984Verschraegen 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.
- New Mexico Cancer Care AllianceLink provided by the sponsor.
- University of New Mexico Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Monte Shaheen, MD principal investigator
University of New Mexico Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Irinotecan&Temsirolimus:Arm1, Level 1, Irinotecan&Temsirolimus:Arm 1, Level 2 and Irinotecan&Temsirolimus:Arm 2, Level 1 in people with Sarcoma, run by New Mexico Cancer Research Alliance 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 4 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 1 Sep 2015. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 1 Sep 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?
Maximum Tolerated Dose (MTD) of Irinotecan (time frame: Up to 1 month). The study lists 2 primary outcomes in all. 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 NCT00996346, which also lists 1 linked publication.
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 1 Sep 2015.