Vemurafenib in Combination With Everolimus or Temsirolimus With Advanced Cancer

NCT01596140 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2012-0153NCI-2012-00789
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Cancer; Solid Tumor

Keywords

Vemurafenib; Everolimus; Afinitor; RAD001; temsirolimus; BRAF gene mutation; solid tumor; relapsed BRAF mutation positive malignant melanoma; refractory BRAF mutation positive malignant melanoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Combination Vemurafenib

  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.

  First cycle of 28 day cycle

Secondary Outcomes (1)

• Tumor Response

  4 months

Study Arms (2)

Vemurafenib + Oral Everolimus

EXPERIMENTAL

Vemurafenib starting dose 720 mg orally twice day (morning/evening) for 28-day cycle plus Oral Everolimus starting dose 5 mg daily.

Drug: Vemurafenib; Drug: Everolimus

Vemurafenib + Intravenous Temsirolimus

EXPERIMENTAL

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; Drug: Temsirolimus

Interventions

Vemurafenib DRUG

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.

Also known as: Zelboraf®, PLX4032, RO5185426

Vemurafenib + Intravenous Temsirolimus; Vemurafenib + Oral Everolimus

Everolimus DRUG

Starting dose 5.0 mg by mouth daily for 28-day study cycle.

Also known as: Afinitor®, RAD001

Vemurafenib + Oral Everolimus

Temsirolimus DRUG

Starting dose 15 mg daily over 30-60 minutes on Days 1, 8, 15, and 22 of each 28-day cycle.

Also known as: Temodar

Vemurafenib + Intravenous Temsirolimus

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Interventions

Vemurafenib; Everolimus; temsirolimus; Temozolomide

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sirolimus; Macrolides; Lactones; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Vivek Subbiah, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2012
• First Posted: May 10, 2012
• Study Start: December 18, 2012
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: June 4, 2020

Record last verified: 2020-06

Locations

US (1)