Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma. (EVOLVE-1)

Novartis

Status and phase: Completed; Phase 3

Conditions: Carcinoma

Treatments: Drug: Everolimus Placebo; Other: Best Supportive Care (BSC); Drug: Everolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT01035229

CRAD001O2301

2009-010196-25 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to compare treatment with RAD001 plus best supportive care (BSC) to placebo plus BSC in patients with advanced HCC whose disease progressed while on or after sorafenib treatment or who are intolerant to sorafenib.

Enrollment: 546 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Advanced liver cancer

• Prior systemic treatment with sorafenib for advanced HCC and for whom their disease progressed during or after sorafenib treatment, or were intolerant to sorafenib treatment. Specifically, this can be defined as:

  • Documented radiological confirmation (radiology scans or report) of disease progression during or after sorafenib treatment
  • Intolerance to sorafenib (at any dose and/or duration) is defined as documented sorafenib-related grade 3 or 4 adverse events that led to sorafenib discontinuation.

NOTE:

• Sorafenib must be the last antineoplastic treatment before randomization

• Prior local and/or hormonal therapy (e.g., tamoxifen) before sorafenib is allowed

• One systemic chemotherapy regimen for advanced HCC is allowed before sorafenib treatment

  • ECOG performance status of ≤ 2
  • Child-Pugh A

Exclusion criteria

• Active bleeding during the last 28 days
• Prior therapy with mTOR inhibitors
• Prior liver or other organ transplantation which mandates systemic immunosuppression

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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546 participants in 2 patient groups, including a placebo group

Everolimus + Best Supportice Care (BSC)

Experimental group

Description:

Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the investigational drug. In addition to taking Everolimus, all patients also received BSC as per normal local practice.

Treatment:

Drug: Everolimus

Other: Best Supportive Care (BSC)

Placebo + Best Supportive Care

Placebo Comparator group

Description:

Placebo Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placeb Everolimus, all patients also received BSC as per normal local practice.

Treatment:

Other: Best Supportive Care (BSC)

Drug: Everolimus Placebo