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Phase I/II Trial of RAD001 Plus Nexavar® For Patients With Metastatic Renal Cell Carcinoma

Phase 1/Phase 2
18 Years
Not Enrolling
Carcinoma, Renal Cell

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Trial Information

Phase I/II Trial of RAD001 Plus Nexavar® For Patients With Metastatic Renal Cell Carcinoma

Despite significant progress in understanding the biology of renal cell carcinoma (RCC), it
is estimated that over 35, 000 people in the United States will be diagnosed and
approximately 12, 000 have died from this disease in 2005. Renal cell carcinoma presently
ranks tenth as the leading cause of cancer death and constitutes 3% of all solid neoplasms.

In contrast to many other malignancies, treatment for RCC is limited. Treatment remains a
highly difficult and perplexing challenge due to its resistance to both chemotherapy and
hormone therapy and limited response to cytokines. Despite recent advances in our
fundamental knowledge of RCC biology and development of molecular therapeutics, more
clinical research will be required to best guide our use of these exciting new agents in
combination regimens.

The combination of RAD001 and Nexavar®, in current clinical trials with minimal toxicity,
represents a treatment regimen which should be investigated for tolerance and toxicity as
well as initial phase II efficacy. The study is designed to evaluate the MTD. Following the
completion of the phase I, utilizing the MTD, Phase II study is designed to evaluate the
anti-tumor activity.

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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

- 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.

- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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).

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Robert J Amato, DO

Investigator Role:

Principal Investigator

Investigator Affiliation:

The Methodist Hospital Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

December 2006

Completion Date:

Related Keywords:

  • Carcinoma, Renal Cell
  • Kidney cancer
  • Renal cell carcinoma
  • Metastatic RCC
  • Carcinoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms



The Methodist Hospital Research Institute Houston, Texas  77030