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

Non-Small Cell Lung Cancer Clinical Trial

— SU/Rapamycin  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00555256
• Other study ID #: 07-0562 / 201101709
• Status: Completed
• Phase: Phase 1
• First received: November 7, 2007
• Last updated: May 5, 2016
• Start date: November 2007
• Est. completion date: December 2012

Study information

• Verified date: March 2013
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: December 2012
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

• 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• sunitinib and rapamycin (Drug will be held)
Any toxicity causing a total of 14 days delay of therapy will be considered dose limiting.

Locations

Country	Name	City	State
United States	Washington University School of medicine	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (29)

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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. — View Citation

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* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To define the optimal dose of sunitinib when given in combination with rapamycin 2mg daily.		6 weeks	Yes
Primary	Determine the dose limiting toxicity of sunitinib and rapamycin		6 weeks	Yes
Secondary	Incidence and severity of other toxicities	Cycles are 6 weeks long and can have as many as 9 cycles	30 days after the end of treatment	Yes
Secondary	Response rates		30 days after end of treatment	No
Secondary	Overall survival		12 months from date of first treatment	No

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine