Vemurafenib in Combination With Everolimus or Temsirolimus With Advanced Cancer
This study is currently recruiting participants.
Verified February 2013 by M.D. Anderson Cancer Center
Sponsor:
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01596140
First received: May 8, 2012
Last updated: February 25, 2013
Last verified: February 2013
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Purpose
The goal of this clinical research study is to find the highest tolerable dose of vemurafenib that can be given in combination with either everolimus or temsirolimus. The safety of these drug combinations will also be studied.
Vemurafenib is designed to block BRAF inside the cancer cells, which is a mutation that is involved in cancer cell growth.
Temsirolimus and everolimus are designed to block the growth of cancer cells, which may cause cancer cells to die.
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced Cancer Solid Tumor |
Drug: Vemurafenib Drug: Everolimus Drug: Temsirolimus |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I Dose-Escalation Study of the BRAF Inhibitor Vemurafenib (Zelboraf®) in Combination With an mTOR Inhibitor, Everolimus (Afinitor®) or Temsirolimus (Torisel®), in Subjects With Advanced Cancer |
Resource links provided by NLM:
Further study details as provided by M.D. Anderson Cancer Center:
Primary Outcome Measures:
- Maximum Tolerated Dose (MTD) of combination Vemurafenib [ Time Frame: First cycle of 28 day cycle ] [ Designated as safety issue: Yes ]The MTD of combination Vemurafenib and Everolimus or Vemurafenib and Temsirolimus is defined as the highest dose studied in which the incidence of dose limiting toxicity (DLT) was less than one third (33%) of the participants at that dose level.
| Estimated Enrollment: | 114 |
| Study Start Date: | December 2012 |
| Estimated Primary Completion Date: | December 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Vemurafenib + Oral Everolimus
Vemurafenib starting dose 720 mg orally twice day (morning/evening) for 28-day cycle plus Oral Everolimus starting dose 5 mg daily.
|
Drug: Vemurafenib
Starting dose 720 mg by mouth twice a day (3 tablets in the morning and 3 tablets in the evening) for 28-day study cycle.
Other Names:
Drug: Everolimus
Starting dose 5.0 mg by mouth daily for 28-day study cycle.
Other Names:
|
|
Experimental: Vemurafenib + Intravenous Temsirolimus
Vemurafenib starting dose 720 mg orally twice day (morning/evening) for 28-day cycle plus Intravenous Temsirolimus starting dose 15 mg daily on Days 1, 8, 15, and 22 of each cycle.
|
Drug: Vemurafenib
Starting dose 720 mg by mouth twice a day (3 tablets in the morning and 3 tablets in the evening) for 28-day study cycle.
Other Names:
Drug: Temsirolimus
Starting dose 15 mg daily over 30-60 minutes on Days 1, 8, 15, and 22 of each 28-day cycle.
Other Name: Temodar
|
Show Detailed Description Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Confirmation of BRAF mutation-positive malignancy is required for selection of patients for vemurafenib therapy
- Measurable or non-measurable disease by RECIST 1.1.
- Patients with advanced cancer should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy available that improves survival by at least three months.
- Patients must be at least 3 weeks past receiving cytotoxic therapy and at least 5 half-lives after their previous treatment or 3 weeks, whichever is shorter, after biologic therapy. Patients may receive palliative radiotherapy immediately or during treatment provided that not all target lesions are radiated.
- ECOG performance status </= 2 (Karnofsky >/= 60%; Lansky Score >/= 50).
- Patients must have normal organ and marrow function defined as: absolute neutrophil count >/=1,000/mL; platelets >/=50,000/mL; creatinine < 2.0; total bilirubin < 2.0; ALT(SGPT) </= 3 X ULN; Exception for patients with liver metastasis: ALT(SGPT) </= 5 X ULN.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Patients with uncontrolled concurrent illness, including but not limited to: ongoing or active infection requiring hospitalization; psychiatric illness/social situations that would limit compliance with study requirements.
- Exclusion of patients with creatinine >2.0 and bilirubin > 2.0.
- Pregnant or lactating women.
- Patients with a history of bone marrow transplant within the previous two years.
- Patients with a known hypersensitivity to any of the components of the drug products.
- Patients with major surgery within 30 days prior to entering the study.
- Patients with a baseline QTc > 500 ms.
- Patients who are unable to swallow pills.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01596140
Contacts
| Contact: Vivek Subbiah, MD | 713-794-1226 |
Locations
| United States, Texas | |
| UT MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
| Principal Investigator: | Vivek Subbiah, MD | UT MD Anderson Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01596140 History of Changes |
| Other Study ID Numbers: | 2012-0153 |
| Study First Received: | May 8, 2012 |
| Last Updated: | February 25, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by M.D. Anderson Cancer Center:
|
Vemurafenib Everolimus Afinitor RAD001 temsirolimus |
BRAF gene mutation solid tumor relapsed BRAF mutation positive malignant melanoma refractory BRAF mutation positive malignant melanoma |
Additional relevant MeSH terms:
|
Neoplasms Everolimus Sirolimus Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Antifungal Agents Anti-Infective Agents Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on May 19, 2013