Clinical trial NCT00419159: Efficacy and Safety of Everolimus in Patients With Metastatic Colorectal Cancer Who Have Failed Prior Targeted Therapy and Chemotherapy
Official title: A Single Arm, Multicenter Phase II Study of Everolimus in Patients With Metastatic Colorectal Adenocarcinoma Whose Cancer Has Progressed Despite Prior Therapy With an Anti-EGFR Antibody (if Appropriate), Bevacizumab, Fluoropyrimidine, Oxaliplatin, and Irinotecan-based Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: Colorectal cancer
metastatic colorectal adenocarcinoma
anti-EGFR antibody
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-01-08
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To assess the safety and efficacy of weekly (70 mg per week) and daily (10 mg per day) everolimus in patients with metastatic colorectal cancer whose cancer has progressed despite prior treatment with targeted therapy and chemotherapy.


Eligibility criteria: Inclusion criteria:

* Age ≥ 18 years old.
* Patients with metastatic colorectal cancer (CRC).
* Patients must have sufficient and obtainable tumor tissue for biomarker analysis from original surgical resection.
* Patients with documented disease progression within 6 months of their most recent dose of chemotherapeutic regimens.
* Patients with at least one measurable lesion.
* Adequate bone marrow function.
* Adequate liver function.
* Adequate renal function.
* Patients with a life expectancy of \> 3 months.
* Patients with a World Health Organization (WHO) performance status of 0, 1, or 2.
* Women of childbearing potential must have had a negative serum pregnancy test 72 hours prior to the administration of the first study treatment.
* Patients who give a written informed consent obtained according to local guidelines.

Exclusion criteria:

* Patients currently receiving anti-cancer agents or who have received these within 4 weeks prior to study entry.
* Patients who have previously received RAD001.
* Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients.
* Chronic treatment with steroids or another immunosuppressive agent.
* Patients with untreated central nervous system (CNS) metastases or neurologically unstable CNS metastases.
* HIV seropositivity.
* Patients with an active, bleeding diathesis. Patients may use enoxaparin.
* Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.
* Patients who have a history of another primary malignancy \< 3 years, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix.
* Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.
* Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to first study treatment.
* Patients unwilling to or unable to comply with the protocol.

Other protocol defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Disease Control Rate (DCR) and Objective Response Rate (ORR) According to the Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Imaging every 8 weeks
measure: The Number of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Imaging every 8 weeks
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Imaging every 8 weeks
measure: Overall Survival (OS)
timeFrame: Every 3 months
measure: Number of Patients Who Died, Had an Serious Adverse Event (SAE), Had Grade 3 to 4 Adverse Event (AE), Discontinued Due to an AE, or Had a Clinical Notable AE by Treatment (tr).
timeFrame: From the first day of treatment until 28 days after discontinuation of study treatment
measure: Biomarker Predictive of Clinical Benefit (DCR by KRAS) on Everolimus (RAD001) 70 mg/Week
timeFrame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
measure: Biomarker Predictive of Clinical Benefit (DCR by KRAS) on Everolimus (RAD001) 10 mg/Day
timeFrame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
measure: Biomarkers Predictive of Clinical Benefit (Median PFS and OS by KRAS ) on Everolimus (RAD001) 70mg/Week
timeFrame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
measure: Biomarkers Predictive of Clinical Benefit (Median PFS and OS by KRAS) on Everolimus (RAD001) 10mg/Day
timeFrame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
measure: Biomarkers Predictive of Clinical Benefit (DCR by PTEN ) on Everolimus (RAD001) 70mg/Week
timeFrame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
measure: Biomarkers Predictive of Clinical Benefit (DCR by PTEN ) on Everolimus (RAD001) 10mg/Day
timeFrame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
measure: Biomarkers Predictive of Clinical Benefit (Median PFS and OS by PTEN ) on Everolimus (RAD001) 70mg/Week
timeFrame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
measure: Biomarkers Predictive of Clinical Benefit (Median PFS and OS by PTEN ) on Everolimus (RAD001) 10mg/Day
timeFrame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: