Temsirolimus in Treating Patients With Cervical Cancer That Is Recurrent, Locally Advanced, Metastatic, or Cannot Be Removed By Surgery

Cervical Adenocarcinoma Clinical Trial

Official title:

A Phase II Study of Temsirolimus (NSC 683864), an mTOR Inhibitor, in Patients With Recurrent, Unresectable, Locally Advanced or Metastatic Carcinoma of the Cervix

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01026792
• Other study ID #: NCI-2014-00268
• Secondary ID: NCI-2014-00268NC
• Status: Completed
• Phase: Phase 2
• First received: December 3, 2009
• Last updated: August 10, 2015
• Start date: December 2009
• Est. completion date: November 2012

Study information

• Verified date: February 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

PRIMARY OBJECTIVES:

I. To assess the efficacy (objective response rate) of temsirolimus given intravenously (IV) weekly in patients with metastatic and/or locally advanced recurrent carcinoma of the cervix.

II. To assess the adverse events, time to progression and response duration of temsirolimus given IV weekly in patients with metastatic and/or locally advanced recurrent carcinoma of the cervix.

III. To explore the relationship between expression of proteins in the mammalian target of rapamycin (mTOR) pathway in archival tissue samples from patients on this trial and their objective response to therapy.

OUTLINE:

Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. For complete responders, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or for 2 courses after complete response criteria are first met. For other patients, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 3 months (patients with complete response [CR], partial response [PR], or stable disease [SD] only) thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: November 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 (ß)-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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Adenosquamous
• Carcinoma, Squamous Cell
• 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
• Uterine Cervical Neoplasms

Intervention

Drug:
• Temsirolimus
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
Canada	National Cancer Institute of Canada Clinical Trials Group	Kingston	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	Response is defined as a 30% decrease in the sum of the longest diameters of the target lesions (PR) or complete disappearance of disease and symptoms (CR) for at least 4 weeks as assessed by Response Evaluation Criteria in Solid Tumors 1.1	Up to 3 years	No