Temsirolimus and Vinorelbine Ditartrate in Treating Patients With Unresectable or Metastatic Solid Tumors
Primary Purpose
Extensive Stage Small Cell Lung Cancer, Hereditary Paraganglioma, Male Breast Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
temsirolimus
vinorelbine ditartrate
Sponsored by
About this trial
This is an interventional treatment trial for Extensive Stage Small Cell Lung Cancer
Eligibility Criteria
Inclusion
- Patients with histologically confirmed metastatic or unresectable solid tumors for which standard curative measures do not exist or are no longer effective; histology will be limited to those tumors for which temsirolimus or vinorelbine have reported clinical activity: lung, breast, ovary, cervix, prostate, uterus, renal, bladder and neuroendocrine tumors
- SWOG performance status of 0-2
- Projected life expectancy of at least 3 months
- Provision of informed consent prior to any study-related procedures
- Negative pregnancy test for women of childbearing potential
- Female patients must not be pregnant due to the potential mutagenicity and teratogenicity of this treatment; a pregnancy test must be administered 7 days prior to administration of therapy to women of childbearing potential; patients must agree to use some form of contraception while on this study at initiation and for the duration of participation in the study; sexually active males must also use a reliable and appropriate method of contraception; post-menopausal women must be amenorrheic for at least 12 months to be considered of nonchildbearing potential
- Patients must have recovered from acute toxicities from previous surgery, chemotherapy or radiation therapy
- ANC >= 1500/mm^3
- Platelet count >= 100,000 cells/mm^3
- Hemoglobin >= 9.0g/dL
- Serum creatinine =< 1.5 mg/dl
- Hepatic function: Patients must have adequate liver functions: AST or ALT =< 2.5 X upper limit of normal (ULN), alkaline phosphatase =< 2.5 X upper limit of normal; in patients with bone metastasis and no evidence of liver metastasis and bilirubin =< upper limit of normal an alkaline phosphatase =< 5 ULN will be allowed
- Serum Bilirubin =< 1.0 mg/dL
- Peripheral neuropathy grade 0-1
- No other concomitant therapy directed at the cancer is allowed
Exclusion
- Prior therapy with vinorelbine or an mTor inhibitor
- Receipt of any investigational agents within 30 days prior to commencing study treatment
- Last dose of prior chemotherapy discontinued less than 4 weeks before the start of study therapy
- Last radiation therapy within the last 4 weeks before the start of study therapy, except palliative radiotherapy
- Any unresolved toxicity greater than CTC grade 1 from previous anticancer therapy, excluding alopecia
- CTC Grade 1 or greater neuropathy (motor or sensory) at study entry
- Hematologic function with absolute neutrophils =< 1500/mm^3 and/or platelets < 100,000/mm^3
- Hepatic function with serum bilirubin greater than the upper institutional limits of normal, ALT and AST > 2.5 times the upper institutional limits of normal
- Concurrent use of strong inhibitors of CYP3A4: ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine and voriconazole
- CYP3A4 inducers should be avoided or used with caution; the use of these agents is discouraged: rifabutin, rifampicin, rifapentine, carbamazepine, Phenobarbital, phenytoin and St. John's wart
- Ongoing long term use of steroids for chronic conditions
Sites / Locations
- USC/Norris Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm I
Arm Description
Patients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22 and vinorelbine ditartrate IV over 5-10 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
To determine the maximum tolerated dose of Temsirolimus and Vinorelbine
To assess the response rate based on the Response Evaluation Criteria in Solid Tumors (RECIST)
Secondary Outcome Measures
To evaluate the safety and tolerability of Temsirolimus and Vinorelbine
Progression-free and overall survival
Full Information
NCT ID
NCT01155258
First Posted
June 30, 2010
Last Updated
June 9, 2016
Sponsor
University of Southern California
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT01155258
Brief Title
Temsirolimus and Vinorelbine Ditartrate in Treating Patients With Unresectable or Metastatic Solid Tumors
Official Title
Phase I Clinical Trial of Temsirolimus and Vinorelbine in Advanced Solid Tumors.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern California
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
RATIONALE: Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as vinorelbine ditartrate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus together with vinorelbine ditartrate may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of giving temsirolimus and vinorelbine ditartrate together in treating patients with unresectable or metastatic solid tumors.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximal tolerated dose (MTD) for the combination of temsirolimus and vinorelbine in advanced solid tumors.
II. To obtain preliminary information regarding the activity of this combination.
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of this combination.
OUTLINE:
Patients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22 and vinorelbine ditartrate IV over 5-10 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Extensive Stage Small Cell Lung Cancer, Hereditary Paraganglioma, Male Breast Cancer, Malignant Paraganglioma, Metastatic Gastrointestinal Carcinoid Tumor, Metastatic Pheochromocytoma, Pancreatic Polypeptide Tumor, Recurrent Breast Cancer, Recurrent Cervical Cancer, Recurrent Endometrial Carcinoma, Recurrent Gastrointestinal Carcinoid Tumor, Recurrent Islet Cell Carcinoma, Recurrent Neuroendocrine Carcinoma of the Skin, Recurrent Non-small Cell Lung Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Ovarian Germ Cell Tumor, Recurrent Pheochromocytoma, Recurrent Prostate Cancer, Recurrent Renal Cell Cancer, Recurrent Small Cell Lung Cancer, Recurrent Uterine Sarcoma, Regional Gastrointestinal Carcinoid Tumor, Regional Pheochromocytoma, Stage III Cervical Cancer, Stage III Endometrial Carcinoma, Stage III Neuroendocrine Carcinoma of the Skin, Stage III Ovarian Epithelial Cancer, Stage III Ovarian Germ Cell Tumor, Stage III Prostate Cancer, Stage III Renal Cell Cancer, Stage III Uterine Sarcoma, Stage IIIA Breast Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Breast Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer, Stage IV Endometrial Carcinoma, Stage IV Neuroendocrine Carcinoma of the Skin, Stage IV Non-small Cell Lung Cancer, Stage IV Ovarian Epithelial Cancer, Stage IV Ovarian Germ Cell Tumor, Stage IV Prostate Cancer, Stage IV Renal Cell Cancer, Stage IV Uterine Sarcoma, Stage IVA Cervical Cancer, Stage IVB Cervical Cancer, Thyroid Gland Medullary Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22 and vinorelbine ditartrate IV over 5-10 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
temsirolimus
Other Intervention Name(s)
CCI-779, cell cycle inhibitor 779, rapamycin analog CCI-779, Torisel
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
vinorelbine ditartrate
Other Intervention Name(s)
Biovelbin, Eunades, navelbine ditartrate, NVB, vinorelbine tartrate, VNB
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
To determine the maximum tolerated dose of Temsirolimus and Vinorelbine
Time Frame
1 month up to 18 months
Title
To assess the response rate based on the Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame
2 months up to 18 months
Secondary Outcome Measure Information:
Title
To evaluate the safety and tolerability of Temsirolimus and Vinorelbine
Time Frame
4 weeks up to 36 weeks
Title
Progression-free and overall survival
Time Frame
Up to 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion
Patients with histologically confirmed metastatic or unresectable solid tumors for which standard curative measures do not exist or are no longer effective; histology will be limited to those tumors for which temsirolimus or vinorelbine have reported clinical activity: lung, breast, ovary, cervix, prostate, uterus, renal, bladder and neuroendocrine tumors
SWOG performance status of 0-2
Projected life expectancy of at least 3 months
Provision of informed consent prior to any study-related procedures
Negative pregnancy test for women of childbearing potential
Female patients must not be pregnant due to the potential mutagenicity and teratogenicity of this treatment; a pregnancy test must be administered 7 days prior to administration of therapy to women of childbearing potential; patients must agree to use some form of contraception while on this study at initiation and for the duration of participation in the study; sexually active males must also use a reliable and appropriate method of contraception; post-menopausal women must be amenorrheic for at least 12 months to be considered of nonchildbearing potential
Patients must have recovered from acute toxicities from previous surgery, chemotherapy or radiation therapy
ANC >= 1500/mm^3
Platelet count >= 100,000 cells/mm^3
Hemoglobin >= 9.0g/dL
Serum creatinine =< 1.5 mg/dl
Hepatic function: Patients must have adequate liver functions: AST or ALT =< 2.5 X upper limit of normal (ULN), alkaline phosphatase =< 2.5 X upper limit of normal; in patients with bone metastasis and no evidence of liver metastasis and bilirubin =< upper limit of normal an alkaline phosphatase =< 5 ULN will be allowed
Serum Bilirubin =< 1.0 mg/dL
Peripheral neuropathy grade 0-1
No other concomitant therapy directed at the cancer is allowed
Exclusion
Prior therapy with vinorelbine or an mTor inhibitor
Receipt of any investigational agents within 30 days prior to commencing study treatment
Last dose of prior chemotherapy discontinued less than 4 weeks before the start of study therapy
Last radiation therapy within the last 4 weeks before the start of study therapy, except palliative radiotherapy
Any unresolved toxicity greater than CTC grade 1 from previous anticancer therapy, excluding alopecia
CTC Grade 1 or greater neuropathy (motor or sensory) at study entry
Hematologic function with absolute neutrophils =< 1500/mm^3 and/or platelets < 100,000/mm^3
Hepatic function with serum bilirubin greater than the upper institutional limits of normal, ALT and AST > 2.5 times the upper institutional limits of normal
Concurrent use of strong inhibitors of CYP3A4: ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine and voriconazole
CYP3A4 inducers should be avoided or used with caution; the use of these agents is discouraged: rifabutin, rifampicin, rifapentine, carbamazepine, Phenobarbital, phenytoin and St. John's wart
Ongoing long term use of steroids for chronic conditions
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Agustin Garcia
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
USC/Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Temsirolimus and Vinorelbine Ditartrate in Treating Patients With Unresectable or Metastatic Solid Tumors
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