AZD2171 and Temsirolimus in Patients With Advanced Gynecological Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
National Comprehensive Cancer Network
Wyeth is now a wholly owned subsidiary of Pfizer
AstraZeneca
Information provided by (Responsible Party):
Susana M. Campos, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01065662
First received: February 8, 2010
Last updated: August 23, 2013
Last verified: August 2013
  Purpose

The purpose of this research study is to determine the safety of the combination of the two drugs cediranib and temsirolimus and the highest doses of these two drugs that can be given in combination to people safely. Cediranib is a drug that may stop blood supply to the tumor and therefore help keep cancer cells from growing. Temsirolimus is a drug that may stop cancer cells from growing. These drugs have been used in other research studies in ovarian and kidney cancer and these studies suggest that these drugs may help to keep cancer from growing in this research study.


Condition Intervention Phase
Endometrial Cancer
Ovarian Cancer
Cervical Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Drug: temsirolimus
Drug: cediranib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/IB Study fo AZD2171 and Temsirolimus in Patients With Advanced Gynecological Malignancies

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To determine the maximum tolerated dose of cediranib with temsirolimus in patients with recurrent/refractory gynecological malignancies. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the efficacy of this combination as measured by response rate or clinical benefit. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: February 2010
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: temsirolimus
    Given on days 1, 8, 15 and 22 of each cycle
    Drug: cediranib
    Taken orally daily
Detailed Description:
  • We are looking for the highest dose of the study drugs that can be administered safely without severe or unmanageable side effects in participants that have recurrent gynecological cancers. Not everyone who participates in this research study will receive the same dose of the study drug.
  • There will be samples of blood taken that measure any additional effect of the study drugs and to look for a marker for the participant's particular type of cancer. Blood will be taken at a certain point in the study to evaluate the interaction of the two study drugs, cediranib and temsirolimus when given together. These are called pharmacokinetic (PK) samples. About 6 teaspoons of blood will be taken with each PK sample with a total of 34 samples taken.
  • Participants will be given a study medication diary for each treatment cycle. Each cycle lasts four weeks (28 days). Temsirolimus will be given on days 1, 8, 15 and 22 of each cycle. Cediranib wil be taken orally once daily in the morning.
  • Participants will be asked to monitor their blood pressure on a daily basis at home and keep a blood pressure diary.
  • The following tests and procedures will be performed at specific time periods during the course of the study: medical history; side effect assessment; physical exam; vital signs; blood tests; CT scan; MUGA or ECHO; EKG and urine test.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with metastatic endometrial cancer
  • Patients with recurrent ovarian, fallopian and peritoneal cancer
  • Patients with recurrent cervical cancer
  • Patients may have either measurable or non-measurable disease
  • Up to one prior line of chemotherapy in the recurrent setting is allowed. Biologic therapies will be considered as a prior line but hormonal therapies do not count.
  • No prior VEGF inhibitor therapy allowed.
  • Toxic side effects related to prior chemotherapy or hormonal therapy must have resolved to less than or equal to grade 1 or to baseline (excluding alopecia), or for peripheral neuropathy to less than or equal to grade 2.
  • Subjects may begin AZD2171 and temsirolimus at least 3 weeks after their last dose of chemotherapy or hormonal therapy, assuming they are otherwise eligible.
  • 18 years of age or older
  • At present, the potential of AZD2171 for clinically significant drug interactions involving the CYP isozymes is unknown. Eligibility of patients receiving any medication or substances known to affect or with teh potential to affect the activity or PK of AZD2171 will be determined following review of their case by the principal investigator.
  • Subjects with treated limited stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible if they otherwise meet eligibility. Subjects with stage I or II cancer treated with curative intent are also eligible with no evidence of recurrent disease.
  • No evidence of preexisting uncontrolled hypertension. If patient has hypertension, it must be medically controlled prior to starting AZD2171.
  • Women of child-bearing potential must have a negative pregnancy test prior to study entry. Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation.
  • No therapeutic anticoagulation. The use of low dose warfarin, intermittent doses of TPA, or heparin flushes to prophylaxis against central venous catheter-associated clots is permitted.
  • ECOG Performance status 0-2
  • Patients must have normal organ and marrow function as defined in the protocol

Exclusion Criteria:

  • Patients who have had chemotherapy, radiotherapy, or major surgery within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
  • Patients may not be receiving any other investigational agents nor have participated in an investigational trial within the past 4 weeks. Prior bevacizumab is allowed.
  • Patients may not be receiving any medication that may markedly affect renal function. NSAIDs should be avoided if possible.
  • Patients with known brain metastases should be excluded from this clinical trial. A CT of the head is required prior to entry into the study.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171.
  • Mean QTc of 470msec or greater in screening electrocardiogram or history of familial long QT syndrome.
  • Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart
  • Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Inability to take and absorb orally administered medication.
  • Pregnant women. Breastfeeding should be discontinued.
  • Major surgical procedure or medical interference with peritoneum or pleura within 4 weeks of baseline CA-125 assessments. This excludes the need for a paracentesis.
  • Subjects with a history of an active malignancy during the last 3 years except non-melanomatous skin cancer, in situ breast or cervical cancer or stage I or II cancer treated with a curative intent and no active cancer recurrence.
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171.
  • New York Heart Association classification of III or IV
  • Conditions requiring concurrent use of drugs or biologics with proarrhythmic potential.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01065662

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Susana M. Campos, MD
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
National Comprehensive Cancer Network
Wyeth is now a wholly owned subsidiary of Pfizer
AstraZeneca
Investigators
Principal Investigator: Susana Campos, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Susana M. Campos, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01065662     History of Changes
Other Study ID Numbers: 09-397
Study First Received: February 8, 2010
Last Updated: August 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
AZD2171
temsirolimus
advanced gynecological malignancies

Additional relevant MeSH terms:
Neoplasms
Endometrial Neoplasms
Uterine Cervical Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Uterine Cervical Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Sirolimus
Everolimus
Cediranib
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014