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CompletedNCT00555256SU/RapamycinUpdated May 6, 2016

A Phase I Study of SUNITINIB and Rapamycin in Advanced Non-Small Cell Lung Cancer (NSCLC)

A Phase 1 interventional study of sunitinib and rapamycin (Drug will be held) in Non-Small Cell Lung Cancer, sponsored by Washington University School of Medicine. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-05-06.

Sponsored by Washington University School of Medicine · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
19
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

To define the optimal dose of sunitinib when given in combination with rapamycin 2mg.

To determine the maximum tolerated dosage of sunitinib and rapamycin given in this fashion.

To determine the how many times and how severe other toxicities of this combination therapy.

To determine how quickly the patient(s) will respond the the drug, overall survival and time to progression for this combination therapy.

Read the detailed description

We propose to conduct a phase I study of sunitinib and rapamycin administered daily for weeks 1-4)in a 6-week cycle. The rationale for this study includes:

  • Sunitinib is a tyrosine kinase inhibitor that targets multiple receptor pathways critical for cell growth. It has both antiangiogenic and direct antitumor activities.
  • Resistance to receptor tyrosine kinase inhibitors is well-documented. The mammalian target of rapamycin (mTOR) pathway may play a critical role in imatinib-refractory GIST. Rapamycin and other agents that inhibit mTOR demonstrate antiangiogenic and antitumor properties by decreasing VEGF production and decreasing responsiveness to VEGF.
  • Sunitinib is approved and well-tolerated at doses as high as 75mg daily. The typical dose in most Phase II and III trials has been 50mg/day, given on a four weeks on/two weeks off schedule. There are, however, recent trials looking at a lower dosage, 37.5 mg, in NSCLC.
  • Rapamycin at doses greater than 2 mg daily is documented to be well-tolerated in renal transplant patients. In renal transplant patients, 2mg daily is the typical starting dose. This dose was used in one of the phase I studies of rapamycin in glioblastoma.
  • The administration of two oral medications, taken once daily, may be more convenient to patients than iv administration of chemotherapy at an infusion center every 1-3 weeks.
  • Based on these data, initial dosing of sunitinib beginning at 37.5 mg orally everyday for 4 weeks, followed by 2 weeks off, in combination with rapamycin 2 mg/day orally for 6 weeks during a 6 week cycle should be well tolerated and allow for dose-finding escalation.
02

Conditions studied

  • Non-Small Cell Lung Cancer

Keywords

  • NSCLC
03

In context

Carcinoma, Non-Small-Cell Lung

6,641 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,665 are open to participants now.

This study's enrollment of 19 is below the median of 62 across 5,327 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.

Browse Carcinoma, Non-Small-Cell Lung studies →

Lead sponsor

Washington University School of Medicine is the lead sponsor of 1,795 studies on the registry; 271 are open to participants now.

Of its 330 completed or terminated interventional studies of FDA-regulated products, 216 (65%) have results posted.

Browse Washington University School of Medicine studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

  • Patients must have a histologically or cytologically proven NSCLC, including adenocarcinoma, broncho-alveolar cell and large cell anaplastic carcinoma
  • Patients need not have measurable disease to be eligible for this study. Patients with non-measurable lesions will be eligible. Measurable and non-measurable disease will be defined by RECIST criteria
  • Age ≥18 years
  • ECOG 0-2
  • Life Expectancy: ≥3 months
  • Patients who have had prior therapy must have completed chemotherapy at least 3 weeks, and radiotherapy at least 2 weeks, prior to study drug administration, with all side effects resolved. Patients who have not received prior therapy are eligible if they are not good candidates for standard treatment with cytotoxic chemotherapy, or do not wish to receive cytotoxic chemotherapy.
  • Patients may not have undergone major surgery within 4 weeks prior to starting study drug administration. In addition, any surgical complications must be resolved, and the surgical scar must be determined by the surgeon to be healing appropriately
  • Patients must have recovered from uncontrolled intercurrent illness including, but not limited to, ongoing active infection
  • Patients may not have had any of the following within 6 months prior to study drug administration: MI, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF, CVA, TIA or PE
  • Patients may not have had a grade 3 hemorrhage within 4 weeks of study drug administration
  • Patients may not have a history of or active spinal cord compression or carcinomatous meningitis. In addition, any previous brain metastases should be adequately treated, and there should be no evidence of new brain or leptomeningeal metastases on a screening CT or MRI scan
  • Patients may not have ongoing cardiac dysrhythmias of grade ≥2. In addition, they may not have a prolonged QTc interval on baseline EKG
  • Patients may not have uncontrolled hypertension or thyroid disease
  • Patients may not have a severe acute or chronic medical or psychiatric condition, or laboratory abnormality
  • Patients must have adequate bone marrow function defined as an absolute neutrophil count ≥ 1,500 cells/mm3, Hgb ≥ 9g/dl and platelet count ≥ 100,000 cells/mm3
  • Patients must have adequate liver function defined as bilirubin \<=2 x the upper limit of institutional normal and SGOT and SGPT \<=2.5 x the upper limit of institutional normal, or SGOT and SGPT \<=5 x the upper limit of institutional normal if liver function abnormalities are due to underlying malignancy
  • Patients must have adequate renal function defined as serum creatinine \<=1.5 x the upper limit of institutional normal
  • Patients must have serum calcium ≤12.0 mg/dL
  • No previous history of severe hypersensitivity reaction attributed to a receptor tyrosine kinase inhibitor.
  • For all patients with reproductive potential, the use of adequate contraception and will be required for the duration of treatment and the 3 months following treatment
  • Pregnant and nursing women are not eligible
  • After being informed of the treatment involved, patients must give written consent. The patient should not have any serious medical or psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment
  • Entry to this study is open to both men and women and to all racial and ethnic subgroups
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
19 participants (actual)

Study arms

  • Experimental
    1

    Patients will be instructed to take sunitinib and rapamycin every morning for 4 weeks, then to take 2 weeks off. The sunitinib dose will be 25mg in the first cohort and the rapamycin dose will be 2 mg.

    Drug: sunitinib and rapamycin (Drug will be held)

Interventions

  • Drugsunitinib and rapamycin (Drug will be held)

    Drug pages: Sunitinib · Sirolimus

    Any toxicity causing a total of 14 days delay of therapy will be considered dose limiting.

06

What researchers measure

Primary outcomes

  1. To define the optimal dose of sunitinib when given in combination with rapamycin 2mg daily.

    Time frame: 6 weeks

  2. Determine the dose limiting toxicity of sunitinib and rapamycin

    Time frame: 6 weeks

Secondary outcomes

  1. Incidence and severity of other toxicities

    Cycles are 6 weeks long and can have as many as 9 cycles

    Time frame: 30 days after the end of treatment

  2. Response rates

    Time frame: 30 days after end of treatment

  3. Overall survival

    Time frame: 12 months from date of first treatment

07

Study locations

1 site
  • Washington University School of medicine
    St Louis, Missouri 63110, United States
08

References and documents

Publications

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  • Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. doi: 10.1056/NEJMoa050753. PubMed 16014882 ↗
  • Abrams TJ, Lee LB, Murray LJ, Pryer NK, Cherrington JM. SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther. 2003 May;2(5):471-8. PubMed 12748309 ↗
  • O'Farrell AM, Abrams TJ, Yuen HA, Ngai TJ, Louie SG, Yee KW, Wong LM, Hong W, Lee LB, Town A, Smolich BD, Manning WC, Murray LJ, Heinrich MC, Cherrington JM. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003 May 1;101(9):3597-605. doi: 10.1182/blood-2002-07-2307. Epub 2003 Jan 16. PubMed 12531805 ↗
  • McKeage MJ, Raynaud F, Ward J, Berry C, O'Dell D, Kelland LR, Murrer B, Santabarabara P, Harrap KR, Judson IR. Phase I and pharmacokinetic study of an oral platinum complex given daily for 5 days in patients with cancer. J Clin Oncol. 1997 Jul;15(7):2691-700. doi: 10.1200/JCO.1997.15.7.2691. PubMed 9215842 ↗
  • Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003 Dec 1;21(23):4342-9. doi: 10.1200/JCO.2003.04.190. PubMed 14645423 ↗
  • Kulke, M., et al., A phase 2 study to evaluate the efficacy and safety of SU11248 in patients (pts) with unresectable neuroendocrine tumors (NETs). J Clin Oncol (Meeting Abstracts), 2005. 23(16_suppl): p. 4008-.
  • Lenz, H., et al., Phase II trial of SU11248 in patients with metastatic colorectal cancer (MCRC) after failure of standard chemotherapy. ASCO Gastrointestinal Cancers Symposium, 2006: p. Abst. No. 241.
  • Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Ginsberg MS, Kim ST, Baum CM, DePrimo SE, Li JZ, Bello CL, Theuer CP, George DJ, Rini BI. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006 Jan 1;24(1):16-24. doi: 10.1200/JCO.2005.02.2574. Epub 2005 Dec 5. PubMed 16330672 ↗
  • Socinski, M.A., et al., Efficacy and safety of Sunitinib in previously treated, advanced non-small cell lung cancer (NSCLC): Preliminary results of a multicenter, phase II trial. Proc Am Soc Clin Oncol, 2006: p. Abst. 7001.
  • Casali, P.G., et al. Updated results from a phase III trial of Sunitinib in GIST patients (pts) for whom imatinib (IM) therapy has failed due to resistance or intolerance. in Proc Am Soc Clin Oncol. 2006.
  • Motzer, R.J., et al., Phase III randomized trial of Sunitinib (SU11248) versus interferon-alfa (IFN-a) as first-line systemic therapy for patients with metastatic renal cell carcinoma (mRCC). Proc Am Soc Clin Oncol, 2006: p. Abst. LBA3.
  • Guba M, von Breitenbuch P, Steinbauer M, Koehl G, Flegel S, Hornung M, Bruns CJ, Zuelke C, Farkas S, Anthuber M, Jauch KW, Geissler EK. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med. 2002 Feb;8(2):128-35. doi: 10.1038/nm0202-128. PubMed 11821896 ↗
  • Smolewski P. Recent developments in targeting the mammalian target of rapamycin (mTOR) kinase pathway. Anticancer Drugs. 2006 Jun;17(5):487-94. doi: 10.1097/00001813-200606000-00001. PubMed 16702804 ↗
  • Busca R, Bertolotto C, Ortonne JP, Ballotti R. Inhibition of the phosphatidylinositol 3-kinase/p70(S6)-kinase pathway induces B16 melanoma cell differentiation. J Biol Chem. 1996 Dec 13;271(50):31824-30. doi: 10.1074/jbc.271.50.31824. PubMed 8943224 ↗
  • Mayerhofer M, Aichberger KJ, Florian S, Krauth MT, Hauswirth AW, Derdak S, Sperr WR, Esterbauer H, Wagner O, Marosi C, Pickl WF, Deininger M, Weisberg E, Druker BJ, Griffin JD, Sillaber C, Valent P. Identification of mTOR as a novel bifunctional target in chronic myeloid leukemia: dissection of growth-inhibitory and VEGF-suppressive effects of rapamycin in leukemic cells. FASEB J. 2005 Jun;19(8):960-2. doi: 10.1096/fj.04-1973fje. Epub 2005 Mar 22. PubMed 15784722 ↗
  • Grewe M, Gansauge F, Schmid RM, Adler G, Seufferlein T. Regulation of cell growth and cyclin D1 expression by the constitutively active FRAP-p70s6K pathway in human pancreatic cancer cells. Cancer Res. 1999 Aug 1;59(15):3581-7. PubMed 10446965 ↗
  • Shapira M, Kakiashvili E, Rosenberg T, Hershko DD. The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells. Breast Cancer Res. 2006;8(4):R46. doi: 10.1186/bcr1533. PubMed 16859513 ↗
  • Chang SM, Wen P, Cloughesy T, Greenberg H, Schiff D, Conrad C, Fink K, Robins HI, De Angelis L, Raizer J, Hess K, Aldape K, Lamborn KR, Kuhn J, Dancey J, Prados MD; North American Brain Tumor Consortium and the National Cancer Institute. Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme. Invest New Drugs. 2005 Aug;23(4):357-61. doi: 10.1007/s10637-005-1444-0. PubMed 16012795 ↗
  • Margolin K, Longmate J, Baratta T, Synold T, Christensen S, Weber J, Gajewski T, Quirt I, Doroshow JH. CCI-779 in metastatic melanoma: a phase II trial of the California Cancer Consortium. Cancer. 2005 Sep 1;104(5):1045-8. doi: 10.1002/cncr.21265. PubMed 16007689 ↗
  • Galanis E, Buckner JC, Maurer MJ, Kreisberg JI, Ballman K, Boni J, Peralba JM, Jenkins RB, Dakhil SR, Morton RF, Jaeckle KA, Scheithauer BW, Dancey J, Hidalgo M, Walsh DJ; North Central Cancer Treatment Group. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J Clin Oncol. 2005 Aug 10;23(23):5294-304. doi: 10.1200/JCO.2005.23.622. Epub 2005 Jul 5. PubMed 15998902 ↗
  • Chan S, Scheulen ME, Johnston S, Mross K, Cardoso F, Dittrich C, Eiermann W, Hess D, Morant R, Semiglazov V, Borner M, Salzberg M, Ostapenko V, Illiger HJ, Behringer D, Bardy-Bouxin N, Boni J, Kong S, Cincotta M, Moore L. Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol. 2005 Aug 10;23(23):5314-22. doi: 10.1200/JCO.2005.66.130. Epub 2005 Jun 13. PubMed 15955899 ↗
  • Atkins 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 14990647 ↗
  • Okuno, S.H., et al., A multicenter phase consortium (P2C) study of the mTOR inhibitor CCI-779 in advanced soft tissue sarcomas (STS). Proc Am Soc Clin Oncol, 2006.
  • Pandya, K.J., et al., A randomized, phase II ECOG trial of two dose levels of temsirolimus (CCI-779) in patients with extensive stage small cell lung cancer in remission after induction chemotherapy. A preliminary report. ASCO Proceedings, 2005: p. Abstract No: 7005.
  • MacDonald AS. Rapamycin in combination with cyclosporine or tacrolimus in liver, pancreas, and kidney transplantation. Transplant Proc. 2003 May;35(3 Suppl):201S-208S. doi: 10.1016/s0041-1345(03)00231-8. PubMed 12742497 ↗
  • Reardon DA, Quinn JA, Vredenburgh JJ, Gururangan S, Friedman AH, Desjardins A, Sathornsumetee S, Herndon JE 2nd, Dowell JM, McLendon RE, Provenzale JM, Sampson JH, Smith RP, Swaisland AJ, Ochs JS, Lyons P, Tourt-Uhlig S, Bigner DD, Friedman HS, Rich JN. Phase 1 trial of gefitinib plus sirolimus in adults with recurrent malignant glioma. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):860-8. doi: 10.1158/1078-0432.CCR-05-2215. PubMed 16467100 ↗
  • Das, A., et al., Phase I study of Gefitinib and rapamycin in patients with recurrent or progressive glioblastoma (GBM). ASCO Proceedings, 2005.
  • Fletcher, J.A., et al., Mechanisms of resistance to imatinib mesylate (IM) in advanced gastrointestinal stromal tumor (GIST). Proc Am Soc Clin Oncol, 2003. 22: p. page 815, (abstr 3275).
09

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Nov 2007, a primary completion of Feb 2010 and a completion of Dec 2012. It does not say whether these dates are actual or estimated.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 7, 2007
First posted
Nov 8, 2007
Start
Nov 2007
Primary completionActual
Feb 2010
CompletionActual
Dec 2012
Last update
May 6, 2016
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on May 6, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00555256
Lead sponsor
Washington University School of Medicine
Collaborators
Pfizer
Responsible party
Sponsor
First posted
Nov 8, 2007
Start date
Nov 2007
Primary completion
Feb 2010
Completion
Dec 2012
Last update
May 6, 2016

Study contacts

Ramaswamy Govindan, M.D.
principal investigator · Washington University School of Medicine

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Mar 2013. You cannot join it, but the record below documents what was studied.

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