Phase I Everolimus Dose Finding Study for the Treatment of Stage IV or Recurrent, Non-resectable, Cervical Cancer With Standard Whole Pelvic Radiation Therapy in Combination With Weekly Cisplatin and Daily Everolimus
Overview
- Phase
- Phase 1
- Intervention
- RAD001
- Conditions
- Cervical Cancer
- Sponsor
- Accelerated Community Oncology Research Network
- Primary Endpoint
- To determine the maximum tolerated dose for RAD001 as adjunct therapy to standard upfront treatment of advanced stage cervical cancer in combination with weekly cisplatin and whole pelvic external beam radiation
- Status
- Withdrawn
- Last Updated
- 12 years ago
Overview
Brief Summary
This Phase 1, single-site, dose-escalation study is being conducted to determine the maximum tolerated dose (MTD) of RAD001 as part of a specified combination regimen.
Detailed Description
This Phase 1, single-site, dose-escalation study is being conducted to determine the MTD of RAD001 as part of a specified combination regimen. The combination regimen will be standard field whole pelvic RT in combination with cisplatin at 40mg/m2 weekly with RAD001 at dose escalation daily starting at 5 mg qod, then 5 mg qd, then 10 mg qd during the period of whole pelvic radiation therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors criteria that has not been previously irradiated.
- •Female patient aged ≥18 years.
- •Patient has life expectancy of at least 12 weeks at study start.
- •Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study start.
- •Patient has diagnosis of stage IV or recurrent, non-resectable, cervical cancer at study start.
- •Patient has received no prior chemotherapy.
- •Patient has adequate hematologic function:
- •Absolute neutrophil count \[ANC\] ≥1500/μL
- •Platelets ≥100,000/μL
- •Hemoglobin \> 9g/dL
Exclusion Criteria
- •Patient has neuroendocrine or small cell carcinoma of the cervix.
- •Patient has previously used any biologic therapy with VEGF, VEGFR, or ErbB1/ErbB2 inhibitors.
- •Patient is currently receiving anticancer therapies or has received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.).
- •Patient has had a major surgery or significant traumatic injury within 4 weeks of start of study drug; patient has not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patient might require major surgery during the course of the study.
- •Patient has had prior treatment with any investigational drug within the preceding 4 weeks before study start.
- •Patient is receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
- •Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Patients should also avoid close contact with people who have received live vaccines during treatment with everolimus. Examples of live vaccines are: intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, and TY21a typhoid vaccines.
- •Patient has known brain or leptomeningeal metastases.
- •Patient has had other malignancies within the past 3 years except for adequately treated squamous cell carcinomas of the skin.
- •Patients has any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
Arms & Interventions
Single arm
All subjects receive RAD001 in combination with standard field whole pelvic radiation and cisplatin.
Intervention: RAD001
Single arm
All subjects receive RAD001 in combination with standard field whole pelvic radiation and cisplatin.
Intervention: Cisplatin
Single arm
All subjects receive RAD001 in combination with standard field whole pelvic radiation and cisplatin.
Intervention: External Beam Whole Pelvis Radiation Therapy
Outcomes
Primary Outcomes
To determine the maximum tolerated dose for RAD001 as adjunct therapy to standard upfront treatment of advanced stage cervical cancer in combination with weekly cisplatin and whole pelvic external beam radiation
Time Frame: every 7 days
To determine the dose limiting toxicities for RAD001 as adjunct therapy to standard upfront treatment of advanced stage cervical cancer in combination with weekly cisplatin and whole pelvic external beam radiation
Time Frame: every 7 days
Secondary Outcomes
- To evaluate microvessel density pre-and post-treatment with the specified treatment regimen in the specified patient population(day 1 and end of treatment)
- To determine the pharmacokinetics of RAD001 given as adjunct therapy to standard upfront treatment of advanced stage cervical cancer(day 1 and day 15 during study treatment)
- To evaluate the pharmacogenetics of RAD001 in the specified patient population(day 1 prior to starting study treatment)
- To evaluate potential correlations between biomarkers HIF-1a, TSP-1, P53, VEGF, and VEGFR and use of the specified treatment regimen in the specified patient population(day 1 and end of treatment)
- To evaluate progression free survival in the specified patient population(from the time of treatment start until progression or up to 5 years after completion of study treatment)
- To assess quality of life as indicated by the Patient Care Monitor in the specified patient population(every 7 days during study treatment)