AZD2171 and Temsirolimus in Patients With Advanced Gynecological Malignancies

NCT01065662 | Completed Phase 1 DMC

• 1 other identifier: 09-397
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

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.

Conditions

Endometrial Cancer; Ovarian Cancer; Cervical Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Keywords

AZD2171; temsirolimus; advanced gynecological malignancies

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose of cediranib with temsirolimus in patients with recurrent/refractory gynecological malignancies.

  1 year

Secondary Outcomes (1)

• To determine the efficacy of this combination as measured by response rate or clinical benefit.

  2 years

Study Arms (1)

Cediranib and Temsirolimus

EXPERIMENTAL

Please see interventions section.

Drug: temsirolimus; Drug: cediranib

Interventions

temsirolimus DRUG

Given on days 1, 8, 15 and 22 of each cycle

Cediranib and Temsirolimus

cediranib DRUG

Taken orally daily

Cediranib and Temsirolimus

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Susana M. Campos, MD: lead
• Massachusetts General Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• National Comprehensive Cancer Network: collaborator
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator
• AstraZeneca: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Endometrial Neoplasms; Ovarian Neoplasms; Uterine Cervical Neoplasms; Fallopian Tube Neoplasms

Interventions

temsirolimus; cediranib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Cervical Diseases; Fallopian Tube Diseases

Study Officials

• Susana Campos, MD

  Dana-Farber Cancer Institute

  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 INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 8, 2010
• First Posted: February 9, 2010
• Study Start: February 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: March 1, 2021
• Last Updated: April 21, 2021

Record last verified: 2021-04

Locations

US (3)