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Vemurafenib in Combination With Everolimus or Temsirolimus With Advanced Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01596140
Recruitment Status : Completed
First Posted : May 10, 2012
Last Update Posted : June 4, 2020
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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 or disease Intervention/treatment Phase
Advanced Cancer Solid Tumor Drug: Vemurafenib Drug: Everolimus Drug: Temsirolimus Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : December 18, 2012
Actual Primary Completion Date : June 1, 2020
Actual Study Completion Date : June 1, 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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:
  • Zelboraf®
  • PLX4032
  • RO5185426

Drug: Everolimus
Starting dose 5.0 mg by mouth daily for 28-day study cycle.
Other Names:
  • Afinitor®
  • RAD001

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:
  • Zelboraf®
  • PLX4032
  • RO5185426

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

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Combination Vemurafenib [ Time Frame: First cycle of 28 day cycle ]
    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. DLT defined as any Grade 3 or 4 non-hematologic toxicity, as defined in NCI CTC v4.0, even if expected and believed related to study medications, any Grade 4 hematologic toxicity lasting two weeks or longer despite supportive care; Grade 3 nausea/vomiting > 48 hours or any Grade 4 nausea/vomiting; and any other Grade 3 non-hematologic toxicity, including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in NCI-CTCAE that is attributable to therapy.

Secondary Outcome Measures :
  1. Tumor Response [ Time Frame: 4 months ]
    Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by RECIST criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in CA125 for patients with ovarian cancer), or (4) a partial response according to Choi criteria, i.e., decrease in size by 10% or more, or a decrease in tumor density, as measured in Hounsfield units (HU), by more than or equal to 15%.

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Confirmation of BRAF mutation-positive malignancy is required for selection of patients for vemurafenib therapy
  2. Measurable or non-measurable disease by RECIST 1.1.
  3. 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.
  4. 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.
  5. ECOG performance status </= 2 (Karnofsky >/= 60%; Lansky Score >/= 50).
  6. 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.
  7. 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.
  8. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. 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.
  2. Exclusion of patients with creatinine >2.0 and bilirubin > 2.0.
  3. Pregnant or lactating women.
  4. Patients with a history of bone marrow transplant within the previous two years.
  5. Patients with a known hypersensitivity to any of the components of the drug products.
  6. Patients with major surgery within 30 days prior to entering the study.
  7. Patients with a baseline QTc > 500 ms.
  8. Patients who are unable to swallow pills.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01596140

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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
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Principal Investigator: Vivek Subbiah, MD M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01596140    
Other Study ID Numbers: 2012-0153
NCI-2012-00789 ( Registry Identifier: NCI CTRP )
First Posted: May 10, 2012    Key Record Dates
Last Update Posted: June 4, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
BRAF gene mutation
solid tumor
relapsed BRAF mutation positive malignant melanoma
refractory BRAF mutation positive malignant melanoma
Additional relevant MeSH terms:
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Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Protein Kinase Inhibitors
Enzyme Inhibitors