Brief Title
AZD2171 and Temsirolimus in Patients With Advanced Gynecological Malignancies
Official Title
A Phase I/IB Study fo AZD2171 and Temsirolimus in Patients With Advanced Gynecological Malignancies
Brief Summary
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.
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
To determine the maximum tolerated dose of cediranib with temsirolimus in patients with recurrent/refractory gynecological malignancies.
Secondary Outcome
To determine the efficacy of this combination as measured by response rate or clinical benefit.
Condition
Endometrial Cancer
Intervention
temsirolimus
Study Arms / Comparison Groups
Cediranib and Temsirolimus
Description: Please see interventions section.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
50
Start Date
February 2010
Completion Date
April 2020
Primary Completion Date
September 2013
Eligibility 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.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Susana Campos, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01065662
Organization ID
09-397
Responsible Party
Sponsor-Investigator
Study Sponsor
Susana M. Campos, MD
Collaborators
Massachusetts General Hospital
Study Sponsor
Susana Campos, MD, Principal Investigator, Dana-Farber Cancer Institute
Verification Date
April 2020