Carcinoma, Non-Small-Cell LungPhase 1/2NCT00921310
Temsirolimus and Pemetrexed for Recurrent or Refractory Non-Small Cell Lung Cancer
A Phase 1/2 study testing Pemetrexed and Temsirolimus in people with Carcinoma, Non-Small-Cell Lung, run by Washington University School of Medicine at 1 site in United States.
Trial summary
To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combination of temsirolimus and pemetrexed, as well as the response rate. The starting dose (Dose Level 1) and schedule of pemetrexed will be 500 mg/m^2 given every 3 weeks and the starting dose (Dose Level 1) for temsirolimus will… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Pemetrexed and Temsirolimus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2009to Apr 2016
- Phase
- Phase 1/2
- 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
- Patients must have histologically or cytologically confirmed diagnosis of NSCLC.
- Patients must have non-squamous histology.
- Patients must have measurable disease (by RECIST criteria), 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.
- Patients may have failed at least one prior platinum-based therapy for NSCLC or be candidates for first-line therapy for advanced disease deemed ineligible to receive platinum-based chemotherapy in the opinion of the treating physician (e.g., Eastern Cooperative Oncology Group (ECOG) performance status of 2, age ≥ 70, chronic medical condition).
- Patients must be at least 4 weeks out from chemotherapy, biological therapy, major surgery, or any investigative therapy and must have recovered from any toxicities. Patients must be at least 2 weeks out from prior radiation therapy and must have recovered from any associated toxicities (with the exception of alopecia).
- Patients must be at least 3 weeks out from immunosuppressive therapy (except corticosteroids used as antiemetics).
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- Age ≥18 years. Because no dosing or adverse event data are currently available on the use of pemetrexed in combination with temsirolimus in patients <18 years of age, children are excluded from this study.
- ECOG performance status 0-2.
- Patients must have normal organ and marrow function as defined below:
- hemoglobin ≥9.0 g/dL
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- total bilirubin ≤1.5 mg/dL
- aspartate aminotransferase (AST)(SGOT)/ alanine aminotransferase (ALT) (SGPT) ≤2.5 X institutional upper limit of normal OR ≤5 X institutional upper limit of normal if enzyme abnormalities are due to liver metastases
- creatinine < 2.0 mg/dL AND/OR
- creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- serum cholesterol < 350 mg/dL
- triglycerides < 300 mg/dL
- The effects of pemetrexed and temsirolimus on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because antifolate antineoplastic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability of the patient (or legally authorized representative if applicable) to understand and the willingness to sign a written informed consent document.
- Both men and women and members of all races and ethnic groups are eligible for this trial.
Who cannot join
- Patients who have had previous treatment with pemetrexed.
- Patients may not be receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, clinically significant hepatic or renal disease or neuropathy greater than grade 2.
- Symptomatic brain metastases
- Presence of a third-space fluid (pleural effusion, ascites etc.) that is uncontrolled by drainage.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to temsirolimus, its metabolites (including sirolimus), its components, and/or polysorbate 80, or to other agents used in the study.
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- Known hypersensitivity to macrolide antibiotics.
- Patients with psychiatric illness/social situations that would limit compliance with study requirements and with premedications of dexamethasone, folic acid and vitamin B12.
- Patients with inability to discontinue all non-steroidal anti-inflammatory drugs (NSAIDS).
- Patients taking anticonvulsant medications (Carbamezapine, phenytoin, fosphenytoin, phenobarbital).
- Patients taking anti-arrhythmic medications (amiodarone, diltiazem and quinidine).
- Patients may not be taking medications known as inhibitors of CYP3A4 (carbamezapine, phenytoin, phenobarbital, rifampin, St. John's wort). Use of inducers of CYP3A4 is discouraged but not specifically prohibited. Dexamethasone as a chronic medication is discouraged.
- Pregnant women are excluded from this study because pemetrexed is an antifolate antineoplastic drug with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pemetrexed, breastfeeding should be discontinued if the mother is treated with pemetrexed. These potential risks may also apply to other agents used in this study.
- Patients with known concomitant genetic or acquired immunosuppressive diseases are excluded. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pemetrexed and temsirolimus. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase I/II Trial of Temsirolimus and Pemetrexed in Recurrent/Refractory Non Small Cell Lung Cancer (NSCLC)
To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combination of temsirolimus and pemetrexed, as well as the response rate. The starting dose (Dose Level 1) and schedule of pemetrexed will be 500 mg/m^2 given every 3 weeks and the starting dose (Dose Level 1) for temsirolimus will be 15 mg given weekly for 3 weeks, to complete 1 cycle. In subsequent cohorts, dose will be escalated or de-escalated. Enrollment to each cohort is based on toxicity experienced at that dose level.
Read the detailed description
- To determine the maximum tolerated dose (MTD) of temsirolimus that could be administered weekly in combination with pemetrexed.
- To determine the dose-limiting toxicity (DLT) of temsirolimus and pemetrexed as well as other toxicities of this combination therapy.
- To describe the response rate of the combination in patients with relapsed/refractory non-small cell lung cancer (NSCLC).
- To describe phospho-Akt and phospho-S6 levels in circulating mononuclear cells before and after treatment.
- To determine the response rates in patients with NSCLC when treated with temsirolimus and pemetrexed.
- To evaluate progression-free survival in patients with NSCLC when treated with temsirolimus and pemetrexed.
- To determine the one-year survival rates in patients with NSCLC when treated with temsirolimus and pemetrexed.
- To describe phospho-Akt and phospho-S6 levels in circulating mononuclear cells before and after treatment.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Pemetrexed, Temsirolimus
- Keywords
- Temsirolimus and pemetrexed for recurrent or refractory NSCLC
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PemetrexedDrug
Also called Alimta
TemsirolimusDrug
Also called Torisel
| Study group | Role | What they receive |
|---|---|---|
| Phase I Dose Level 1 (pemetrexed + temsirolimus) | Experimental | -Dose Level 1
* Pemetrexed 500mg/m^2 intravenous (IV) on Day 1 of each 21 day cycle
* Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle Receives: Drug: Pemetrexed; Drug: Temsirolimus |
| Phase I Dose Level -1 (pemetrexed + temsirolimus) | Experimental | * Pemetrexed (375 mg/m^2) IV on Day 1 of each 21 day cycle
* Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle Receives: Drug: Pemetrexed; Drug: Temsirolimus |
| Phase 2 (pemetrexed + temsirolimus) | Experimental | * Phase 2 dose will be the maximum tolerated dose found in the Phase I portion of the study.
* Pemetrexed (375 mg/m^2) IV on Day 1 of each 21 day cycle
* Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle Receives: Drug: Pemetrexed; Drug: Temsirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I Only: Maximum Tolerated Dose (MTD) of Pemetrexed That Could be Administered Weekly in Combination With Temsirolimus
The starting dose and schedule of pemetrexed will be 500 mg/m2 given every 3 weeks and the starting dose for temsirolimus will be 15 mg given weekly for 3 weeks, to complete 1 cycle. In subsequent cohorts, dose will be escalated or de-escalated. Enrollment to each cohort is based on toxicity experienced at that dose level. The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort experience dose-limiting toxicity during the first cycle. Six patients will be enrolled at the maximum tolerated dose to ensure that no more than 2 DLTs occur at the MTD. Dose escalations will proceed until the MTD has been reached.
Measured: Completion of first cycle by all enrolled patients in Phase I portion of study
Phase I Only: Maximum Tolerated Dose (MTD) of Temsirolimus That Could be Administered Weekly in Combination With Pemetrexed
The starting dose and schedule of pemetrexed will be 500 mg/m2 given every 3 weeks and the starting dose for temsirolimus will be 15 mg given weekly for 3 weeks, to complete 1 cycle. In subsequent cohorts, dose will be escalated or de-escalated. Enrollment to each cohort is based on toxicity experienced at that dose level. The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort experience dose-limiting toxicity during the first cycle. Six patients will be enrolled at the maximum tolerated dose to ensure that no more than 2 DLTs occur at the MTD. Dose escalations will proceed until the MTD has been reached.
Measured: Completion of first cycle by all enrolled patients in Phase I portion of study
Phase I Only: Number of Participants Who Experience Dose-limiting Toxicities (DLT) of Temsirolimus and Pemetrexed
DLT will be defined as occurring within the first cycle of Phase I only and will be graded according to the Common Terminology Criteria for Adverse Events v 3.0 (CTCAE)
- Any grade 3 or higher hematologic toxicity with the exception of anemia.
- Any grade 3 or higher non-hematologic toxicity related to study therapy (except alopecia).
- Grade 3 or 4 pneumonitis or esophagitis.
- Treatment delay of temsirolimus for more than 14 consecutive days due to study-related toxicity.
- Treatment delay of pemetrexed therapy for more than 14 consecutive days because of study-related toxicity.
Measured: Completion of first cycle (approximately 21 days)
Phase I and Phase II: Overall Response Rate (Complete Response + Partial Response)
- Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.
- Complete response (CR)-disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level.
- Partial response (PR)-at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD
Measured: 2 years
Phase I Only: Phospho-Akt Levels in Circulating Mononuclear Cells
Measured: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8
Phase I Only: Phospho-S6 Levels in Circulating Mononuclear Cells
Measured: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8
Secondary outcomes (4)
Phase 2 Only: Progression-free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression.
Measured: 2 years from completion of treatment
Phase 2 Only: Survival Rate
Measured: 1 year after start of treatment
Phase 2 Only: Phospho-Akt Levels in Circulating Mononuclear Cells
Measured: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8
Phase 2 Only: Phospho-S6 Levels in Circulating Mononuclear Cells Before and After Treatment
Measured: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2009 (estimated)
- Study startSep 2009
- Primary completionJan 2013
- Study completionApr 2016
Why it stopped: Withdrawal of funding from sponsor
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 (6)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maria Baggstrom, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00921310
- Sponsor's protocol ID
- 09-0668 / 201105207
- Status last verified
- Oct 2016
- First submitted
- 15 Jun 2009
- Last updated
- 13 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Russo F, Bearz A, Pampaloni G; Investigators of Italian Pemetrexed Monotherapy of NSCLC Group. Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer. BMC Cancer. 2008 Jul 31;8:216. doi: 10.1186/1471-2407-8-216.
PubMed 18667090Pal SK, Figlin RA, Reckamp KL. The role of targeting mammalian target of rapamycin in lung cancer. Clin Lung Cancer. 2008 Nov;9(6):340-5. doi: 10.3816/CLC.2008.n.049.
PubMed 19073516Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes GR, Park Y, Liou SH, Marshall B, Boni JP, Dukart G, Sherman ML. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol. 2004 Mar 1;22(5):909-18. doi: 10.1200/JCO.2004.08.185.
PubMed 14990647Rini BI. Temsirolimus, an inhibitor of mammalian target of rapamycin. Clin Cancer Res. 2008 Mar 1;14(5):1286-90. doi: 10.1158/1078-0432.CCR-07-4719. No abstract available.
PubMed 18316545Duran I, Kortmansky J, Singh D, Hirte H, Kocha W, Goss G, Le L, Oza A, Nicklee T, Ho J, Birle D, Pond GR, Arboine D, Dancey J, Aviel-Ronen S, Tsao MS, Hedley D, Siu LL. A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. Br J Cancer. 2006 Nov 6;95(9):1148-54. doi: 10.1038/sj.bjc.6603419. Epub 2006 Oct 10.
PubMed 17031397Peralba JM, DeGraffenried L, Friedrichs W, Fulcher L, Grunwald V, Weiss G, Hidalgo M. Pharmacodynamic Evaluation of CCI-779, an Inhibitor of mTOR, in Cancer Patients. Clin Cancer Res. 2003 Aug 1;9(8):2887-92.
PubMed 12912932
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Temsirolimus and Pemetrexed in Recurrent/Refractory Non Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT00921310
- Acronym / sponsor ID
- 09-0668 / 201105207
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- Temsirolimus and pemetrexed for recurrent or refractory NSCLC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Withdrawal of funding from sponsor
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Jan 2013 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 16 Jun 2009 (estimated)
- Results
- Posted 13 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combination of temsirolimus and pemetrexed, as well as the response rate. The starting dose (Dose Level 1) and schedule of pemetrexed will be 500 mg/m^2 given every 3 weeks and the starting dose (Dose Level 1) for temsirolimus will be 15 mg given weekly for 3 weeks, to complete 1 cycle. In subsequent cohorts, dose will be escalated or de-escalated. Enrollment to each cohort is based on toxicity experienced at that dose level.
Detailed description
- To determine the maximum tolerated dose (MTD) of temsirolimus that could be administered weekly in combination with pemetrexed.
- To determine the dose-limiting toxicity (DLT) of temsirolimus and pemetrexed as well as other toxicities of this combination therapy.
- To describe the response rate of the combination in patients with relapsed/refractory non-small cell lung cancer (NSCLC).
- To describe phospho-Akt and phospho-S6 levels in circulating mononuclear cells before and after treatment.
- To determine the response rates in patients with NSCLC when treated with temsirolimus and pemetrexed.
- To evaluate progression-free survival in patients with NSCLC when treated with temsirolimus and pemetrexed.
- To determine the one-year survival rates in patients with NSCLC when treated with temsirolimus and pemetrexed.
- To describe phospho-Akt and phospho-S6 levels in circulating mononuclear cells before and after treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase I Dose Level 1 (pemetrexed + temsirolimus) | Experimental | Drug: Pemetrexed, Drug: Temsirolimus-Dose Level 1 * Pemetrexed 500mg/m^2 intravenous (IV) on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle |
| Phase I Dose Level -1 (pemetrexed + temsirolimus) | Experimental | Drug: Pemetrexed, Drug: Temsirolimus* Pemetrexed (375 mg/m^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle |
| Phase 2 (pemetrexed + temsirolimus) | Experimental | Drug: Pemetrexed, Drug: Temsirolimus* Phase 2 dose will be the maximum tolerated dose found in the Phase I portion of the study. * Pemetrexed (375 mg/m^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patients must have histologically or cytologically confirmed diagnosis of NSCLC.
- Patients must have non-squamous histology.
- Patients must have measurable disease (by RECIST criteria), 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.
- Patients may have failed at least one prior platinum-based therapy for NSCLC or be candidates for first-line therapy for advanced disease deemed ineligible to receive platinum-based chemotherapy in the opinion of the treating physician (e.g., Eastern Cooperative Oncology Group (ECOG) performance status of 2, age ≥ 70, chronic medical condition).
- Patients must be at least 4 weeks out from chemotherapy, biological therapy, major surgery, or any investigative therapy and must have recovered from any toxicities. Patients must be at least 2 weeks out from prior radiation therapy and must have recovered from any associated toxicities (with the exception of alopecia).
Key exclusion criteria (14 listed)
- Patients who have had previous treatment with pemetrexed.
- Patients may not be receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, clinically significant hepatic or renal disease or neuropathy greater than grade 2.
- Symptomatic brain metastases
- Presence of a third-space fluid (pleural effusion, ascites etc.) that is uncontrolled by drainage.
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 |
|---|---|---|
| PemetrexedAlso: Alimta | Drug | Phase 2 (pemetrexed + temsirolimus), Phase I Dose Level -1 (pemetrexed + temsirolimus), Phase I Dose Level 1 (pemetrexed + temsirolimus) |
| TemsirolimusAlso: Torisel | Drug | Phase 2 (pemetrexed + temsirolimus), Phase I Dose Level -1 (pemetrexed + temsirolimus), Phase I Dose Level 1 (pemetrexed + temsirolimus) |
Primary outcome
Phase I Only: Maximum Tolerated Dose (MTD) of Pemetrexed That Could be Administered Weekly in Combination With Temsirolimus
Time frame: Completion of first cycle by all enrolled patients in Phase I portion of study
The starting dose and schedule of pemetrexed will be 500 mg/m2 given every 3 weeks and the starting dose for temsirolimus will be 15 mg given weekly for 3 weeks, to complete 1 cycle. In subsequent cohorts, dose will be escalated or de-escalated. Enrollment to each cohort is based on toxicity experienced at that dose level. The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort experience dose-limiting toxicity during the first cycle. Six patients will be enrolled at the maximum tolerated dose to ensure that no more than 2 DLTs occur at the MTD. Dose escalations will proceed until the MTD has been reached.
Phase I Only: Maximum Tolerated Dose (MTD) of Temsirolimus That Could be Administered Weekly in Combination With Pemetrexed
Time frame: Completion of first cycle by all enrolled patients in Phase I portion of study
The starting dose and schedule of pemetrexed will be 500 mg/m2 given every 3 weeks and the starting dose for temsirolimus will be 15 mg given weekly for 3 weeks, to complete 1 cycle. In subsequent cohorts, dose will be escalated or de-escalated. Enrollment to each cohort is based on toxicity experienced at that dose level. The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort experience dose-limiting toxicity during the first cycle. Six patients will be enrolled at the maximum tolerated dose to ensure that no more than 2 DLTs occur at the MTD. Dose escalations will proceed until the MTD has been reached.
Phase I Only: Number of Participants Who Experience Dose-limiting Toxicities (DLT) of Temsirolimus and Pemetrexed
Time frame: Completion of first cycle (approximately 21 days)
DLT will be defined as occurring within the first cycle of Phase I only and will be graded according to the Common Terminology Criteria for Adverse Events v 3.0 (CTCAE) * Any grade 3 or higher hematologic toxicity with the exception of anemia. * Any grade 3 or higher non-hematologic toxicity related to study therapy (except alopecia). * Grade 3 or 4 pneumonitis or esophagitis. * Treatment delay of temsirolimus for more than 14 consecutive days due to study-related toxicity. * Treatment delay of pemetrexed therapy for more than 14 consecutive days because of study-related toxicity.
Phase I and Phase II: Overall Response Rate (Complete Response + Partial Response)
Time frame: 2 years
* Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. * Complete response (CR)-disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR)-at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD
Phase I Only: Phospho-Akt Levels in Circulating Mononuclear Cells
Time frame: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8
Phase I Only: Phospho-S6 Levels in Circulating Mononuclear Cells
Time frame: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8
4 secondary outcomes
Phase 2 Only: Progression-free Survival (PFS)
Time frame: 2 years from completion of treatment
Phase 2 Only: Survival Rate
Time frame: 1 year after start of treatment
Phase 2 Only: Phospho-Akt Levels in Circulating Mononuclear Cells
Time frame: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8
Phase 2 Only: Phospho-S6 Levels in Circulating Mononuclear Cells Before and After Treatment
Time frame: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18667090Russo F, Bearz A, Pampaloni G; Investigators of Italian Pemetrexed Monotherapy of NSCLC Group. Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer. BMC Cancer. 2008 Jul 31;8:216. doi: 10.1186/1471-2407-8-216.
- Background: PubMed 19073516Pal SK, Figlin RA, Reckamp KL. The role of targeting mammalian target of rapamycin in lung cancer. Clin Lung Cancer. 2008 Nov;9(6):340-5. doi: 10.3816/CLC.2008.n.049.
- Background: PubMed 14990647Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes GR, Park Y, Liou SH, Marshall B, Boni JP, Dukart G, Sherman ML. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol. 2004 Mar 1;22(5):909-18. doi: 10.1200/JCO.2004.08.185.
- Background: PubMed 18316545Rini BI. Temsirolimus, an inhibitor of mammalian target of rapamycin. Clin Cancer Res. 2008 Mar 1;14(5):1286-90. doi: 10.1158/1078-0432.CCR-07-4719. No abstract available.
- Background: PubMed 17031397Duran I, Kortmansky J, Singh D, Hirte H, Kocha W, Goss G, Le L, Oza A, Nicklee T, Ho J, Birle D, Pond GR, Arboine D, Dancey J, Aviel-Ronen S, Tsao MS, Hedley D, Siu LL. A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. Br J Cancer. 2006 Nov 6;95(9):1148-54. doi: 10.1038/sj.bjc.6603419. Epub 2006 Oct 10.
- Background: PubMed 12912932Peralba JM, DeGraffenried L, Friedrichs W, Fulcher L, Grunwald V, Weiss G, Hidalgo M. Pharmacodynamic Evaluation of CCI-779, an Inhibitor of mTOR, in Cancer Patients. Clin Cancer Res. 2003 Aug 1;9(8):2887-92.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
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Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
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.
Maria Baggstrom, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pemetrexed and Temsirolimus in people with Carcinoma, Non-Small-Cell Lung, run by Washington University School of Medicine 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 21 inclusion and 14 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 13 Dec 2016. 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 combined 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.
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 13 Dec 2016). 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?
Phase I Only: Maximum Tolerated Dose (MTD) of Pemetrexed That Could be Administered Weekly in Combination With Temsirolimus (time frame: Completion of first cycle by all enrolled patients in Phase I portion of study). The study lists 6 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 NCT00921310, which also lists 6 linked publications.
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 13 Dec 2016.