Everolimus Dose Finding Study for Stage IV or Recurrent Cervical Cancer

NCT00967928 | Withdrawn Phase 1

• 1 other identifier: ATDTCC0801
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Cervical Cancer

Keywords

Stage IV or Recurrent Cervical cancer

Outcome Measures

Primary Outcomes (2)

• 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

  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

  every 7 days

Secondary Outcomes (6)

• 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 microvessel density pre-and post-treatment with the specified treatment regimen in the specified patient population

  day 1 and end of 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

Study Arms (1)

Single arm

EXPERIMENTAL

All subjects receive RAD001 in combination with standard field whole pelvic radiation and cisplatin.

Drug: RAD001; Drug: Cisplatin; Radiation: External Beam Whole Pelvis Radiation Therapy

Interventions

RAD001 DRUG

RAD001 will be administered orally as 5 mg qod, 5 mg qd, or 10mg qd continuously from study Day 1 until the end of whole pelvic radiation therapy unless the patient develops progression of disease or unacceptable toxicity prior to that.

Also known as: Afinitor, Everolimus

Single arm

Cisplatin DRUG

Cisplatin will be administered intravenously once weekly at 40mg/m2 for 6 weeks. The preferred administration day is Monday.

Also known as: CDDP, Platinol

Single arm

External Beam Whole Pelvis Radiation Therapy RADIATION

Patients will receive 180 cGy daily fraction Monday through Friday x 25 days (4500 cGy total) using a four field technique throughout the entire treatment with all fields treated each day.

Single arm

Eligibility Criteria

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

You may qualify if:

• 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
• Patient has adequate renal function:
• Serum creatinine ≤ 2.0 mg/dL
• Calculated creatinine clearance ≥ 50 mL/min
• Patient has adequate hepatic function:
• Serum bilirubin ≤1.5 x ULN

You may not qualify if:

• 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:
• Symptomatic congestive heart failure of New York Heart Association Class III or IV.
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
• Severely impaired lung function defined as spirometry and diffusing capacity (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air.
• Uncontrolled diabetes as defined by fasting serum glucose \>1.5 × ULN.
• Active (acute or chronic) or uncontrolled severe infections.

Sponsors & Collaborators

• Accelerated Community Oncology Research Network: lead
• Novartis Pharmaceuticals: collaborator

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Everolimus; Cisplatin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Todd D Tillmanns, MD

  The West Clinic

  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: August 27, 2009
• First Posted: August 28, 2009
• Study Start: December 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: February 14, 2014

Record last verified: 2014-02