Phase I/II Trial of RAD001 Plus Nexavar in Patients With Kidney Cancer

NCT00448149 | Completed Phase 1

• 2 other identifiers: PAC IRB#1006-0152RCC-06-102
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see whether the combination for RAD001 and Nexavar® works better when given together than they do alone. The purpose of the first phase of this study is to determine the best dose of RAD001 given with Nexavar®, and to see what effects, good and/or bad, the study drug has on the subject and the subject's tumor. This study will also observe side effects experienced by the subject.

Conditions

Carcinoma, Renal Cell

Keywords

Kidney cancer; Renal cell carcinoma; Metastatic RCC

Outcome Measures

Primary Outcomes (2)

• Phase I: To establish the maximally tolerated dose (MTD) and safety profile of RAD001 in combination with Nexavar® in patients with metastatic renal cell carcinoma (MRCC).

  1 year

• Phase II: Study the anti-tumor effects of RAD001 plus Nexavar®

  2 years

Secondary Outcomes (5)

• Phase II: Response rate

  restaging every 8 weeks

• Duration of tumor response

  restaging every 8 weeks

• Progression free survival

  restaging every 8 weeks

• Overall survival

  restaging every 8 weeks

• Study the safety of RAD001 plus Nexavar® given at MTD.

  AEs as occur

Study Arms (1)

1

EXPERIMENTAL

To establish the maximally tolerated dose (MTD) of RAD001 in combination with Nexavar®

Drug: RAD001; Drug: Sorafenib

Interventions

RAD001 DRUG

RAD001 will be administered orally once a day, daily, without interruption per 4 wk cycle for 2 cycles. MTD is established in Phase I portion of trial (2.5, 5 or 10mg). If responding, additional therapy will be given.

Also known as: Everolimus

1

Sorafenib DRUG

A dose of 400mg of Nexavar® will be administered orally twice a day, daily, without an interruption per 4 week cycle for 2 cycles. If responding, additional therapy will be given.

Also known as: Nexavar®, BAY-4900

1

Eligibility Criteria

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

You may qualify if:

• Histologic confirmed predominant clear cell renal cell carcinoma.
• Patients must have progressive metastatic disease.
• Paraffin RCC tissue blocks or unstained slides must be available.
• Karnofsky performance status \> 70% .
• Not pregnant
• Age \> 18
• Initial laboratory values must meet requirements
• Phase I: No more than three prior systemic and/or investigative therapy for MRCC. Previous therapy may include prior single agent exposure to RAD001 or Nexavar®. Four weeks must have elapsed from previous therapy.
• Phase II: No more than one prior systemic and/or investigative therapy of any kind for MRCC. Four weeks must have elapsed from previous therapy.
• Phase II: Previous therapy may not include RAD001 or Nexavar®.
• Phase II: Patients with primary tumor in place are strongly encouraged to undergo nephrectomy prior to initiation of study agent.
• Phase II: Prior palliative radiotherapy to metastatic lesion(s) is permitted. Patient must have adequately recovered from the acute toxicities of this treatment.
• Phase II: All major surgery of any type and/or radiotherapy must be completed at least 4 weeks prior to registration.

You may not qualify if:

• No ongoing hemoptysis or cerebrovascular accident within 12 months, or peripheral vascular disease with claudication on less than 1 block, or history of clinically significant bleeding.
• No deep venous thrombosis or pulmonary embolus within one year and no ongoing need for full-dose oral or parenteral anticoagulation.
• No evidence of current central nervous system (CNS) metastases.
• No significant cardiovascular disease
• No patients with uncontrolled hypertension
• Any ongoing requirement for systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency) or other immunosuppressants are not permitted.
• Patients with a pre-existing thyroid abnormality whose thyroid function cannot be maintained in the normal range by medication are ineligible.
• No uncontrolled psychiatric disorder.
• Patients with delayed healing of wounds, ulcers, and/or bone fractures are not eligible.
• Patients with a 'currently active' second malignancy other than non-melanoma skin cancers are not eligible. Patients are not considered to have a 'currently active' malignancy if they have completed anti-cancer therapy and are considered by their physician to be a less than 30% risk of relapse.
• Pregnant women are excluded
• All fertile patients must use adequate contraception (barrier method) while on study and for three months thereafter. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
• Prior treatment with any investigational drug within the preceding 4 weeks.
• Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, severe infection, severe malnutrition, ventricular arrhythmias, chronic liver or renal disease, active upper GI tract ulceration).
• A known history of HIV seropositivity.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

The Methodist Hospital Research Institute

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

Everolimus; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Robert J Amato, DO

  Baylor College of Medicine - Methodist Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 15, 2007
• First Posted: March 16, 2007
• Study Start: December 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: March 17, 2016

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)