Temsirolimus in Treating Patients With Cervical Cancer That Is Recurrent, Locally Advanced, Metastatic, or Cannot Be Removed By Surgery
Condition: Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer
MeSH terms: Carcinoma; Uterine Cervical Neoplasms; Carcinoma, Adenosquamous; Recurrence
Intervention: Temsirolimus; Laboratory Biomarker Analysis
Intervention description: Given IV; Correlative studies
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the effects of temsirolimus in treating patients with cervical
      cancer that cannot be cured by standard therapy. Temsirolimus interferes with a protein in
      cells that is part of one pathway that sends signals to stimulate cell growth and survival.
      By blocking this protein cancer cells may stop growing or die.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed squamous cell carcinoma
             or adenosquamous carcinoma of the cervix, or adenocarcinoma of the cervix

          -  Patients must have unresectable, locally advanced or metastatic disease, incurable by
             standard therapies

          -  Patients must have tumor tissue from their primary tumor available

          -  Presence of clinically and/or radiologically documented disease

               -  Chest x-ray >= 20 mm

               -  Computed tomography (CT) scan (with slice thickness of =< 5 mm) >= 10 mm: longest
                  diameter

               -  Physical exam (using calipers) >= 10 mm

               -  Lymph nodes by CT scan >= 15 mm: measured in short axis

               -  All radiology studies must be performed within 21 days prior to registration
                  (within 28 days if negative)

          -  Patients must have a life expectancy of at least 12 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

          -  Patients may have had up to one prior chemotherapy regimen; a minimum of 28 days (4
             weeks) must have elapsed between the end of chemotherapy and study registration; Note:
             Radiotherapy with concurrent radiosensitizing cisplatin at the time of initial
             diagnosis and treatment is permitted, and is not considered systemic chemotherapy

          -  Patients may have had prior radiation therapy; a minimum of 28 days must have elapsed
             between the end of radiotherapy and registration onto the study; (exceptions may be
             made however, for low dose, palliative radiotherapy); patients must have recovered
             from any acute toxic effects from radiation prior to registration

          -  Previous major surgery is permitted provided that it has been at least 28 days prior
             to patient registration and that wound healing has occurred

          -  Granulocytes (AGC) >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Serum creatinine =< 1.5 upper limit of normal (ULN)

          -  Bilirubin =< 1.5 ULN

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

          -  Fasting serum cholesterol =< 9.0 mmol/L

          -  Fasting triglycerides =< 2.5 x ULN

          -  Patient consent must be obtained according to local Institutional and/or University
             Human Experimentation Committee requirements; it will be the responsibility of the
             local participating investigators to obtain the necessary local clearance, and to
             indicate in writing to the National Cancer Institute of Canada (NCIC) Clinical Trials
             Group (CTG) study coordinator that such clearance has been obtained, before the trial
             can commence in that center; a standard consent form for the trial will not be
             provided but a sample form is given; a copy of the initial full board Research Ethics
             Board (REB) approval and approved consent form must be sent to the central office; the
             patient must sign the consent form prior to registration; please note that the consent
             form for this study must contain a statement which gives permission for the NCIC CTG
             and monitoring agencies to review patient records

          -  Patients must be accessible for treatment, response assessment and follow-up; patients
             registered on this trial must be treated and followed at the participating center;
             this implies there must be reasonable geographical limits (for example: 1 ½ hour's
             driving distance) placed on patients being considered for this trial; investigators
             must assure themselves the patients registered on this trial will be available for
             complete documentation of the treatment, adverse events, and follow-up

          -  In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working
             days of patient registration

        Exclusion Criteria:

          -  Patients with a history of other malignancies, except: adequately treated non-melanoma
             skin cancer or other solid tumors curatively treated with no evidence of disease for
             >= 5 years

          -  Patients must not have had prior treatment with an mTOR inhibitor

          -  Pregnant or lactating women; pregnant women are excluded from this study;
             breastfeeding should be discontinued if the mother is treated with temsirolimus; if
             the patient is of childbearing potential, a urine beta (β)-human chorionic
             gonadotropin (HCG) must be proved negative within 7 days prior to registration; women
             of child-bearing potential must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry and for the duration
             of study participation; should a woman become pregnant or suspect she is pregnant
             while participating in this study, she should inform her treating physician
             immediately

          -  Patients with known brain metastases (a brain CT is not necessary to rule out brain
             metastases, unless there is clinical suspicion of CNS involvement); patients with
             known brain metastases will be excluded from this trial

          -  Patients with serious cardiovascular illness such as myocardial infarction within 6
             months prior to entry, congestive heart failure (even if medically controlled),
             unstable angina, active cardiomyopathy, unstable ventricular arrhythmia or
             uncontrolled hypertension

          -  Patients who require use of therapeutic anticoagulation are ELIGIBLE but must have
             their prothrombin time (PT)/international normalized ratio (INR) or partial
             thromboplastin time (PTT) monitored closely during therapy

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to temsirolimus

          -  Patients receiving concurrent treatment with other anti-cancer therapy or other
             investigational agents

          -  Serious illness or medical condition which would not permit the patient to be managed
             according to the protocol including, but not limited to:

               -  History of significant neurologic or psychiatric disorder which would impair the
                  ability to obtain consent or limit compliance with study requirements

               -  Active uncontrolled infection or non-healing wounds

               -  Active peptic ulcer disease

               -  Active bleeding or any other medical conditions that might be aggravated by
                  treatment

               -  Symptomatic congestive heart failure, unstable angina, cardiac arrhythmia

               -  Fistula or history of fistula at any location, gastrointestinal (GI) perforation
                  or abscess; patients believed to be at high risk for fistula formation because of
                  the location and extent of their disease should not be enrolled