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A Phase II Evaluation of Temsirolimus (CCI-779) (NCI Supplied Agent: NSC# 683864, IND# 61010) in Combination With Carboplatin and Paclitaxel Followed by Temsirolimus (CCI-779) Consolidation as First-Line Therapy in the Treatment of Stage III-IV Clear Cell Carcinoma of the Ovary


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Ovarian Clear Cell Cystadenocarcinoma, Stage III Ovarian Epithelial Cancer, Stage IV Ovarian Epithelial Cancer

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Trial Information

A Phase II Evaluation of Temsirolimus (CCI-779) (NCI Supplied Agent: NSC# 683864, IND# 61010) in Combination With Carboplatin and Paclitaxel Followed by Temsirolimus (CCI-779) Consolidation as First-Line Therapy in the Treatment of Stage III-IV Clear Cell Carcinoma of the Ovary


PRIMARY OBJECTIVES:

I. To assess the activity of the study regimen as measured by the proportion of patients who
are alive and progression-free for at least 12 months after study entry in patients with
newly diagnosed Stage III or IV clear cell ovarian cancer in the following populations:
patients in the U.S. and worldwide (outside of Japan) and patients in Japan.

II. To compare progression-free survival in newly diagnosed Stage III or IV clear cell
ovarian cancer patients in patients in the U.S. and worldwide (outside of Japan) versus
patients in Japan.

SECONDARY OBJECTIVES:

I. To characterize the duration of overall survival and progression-free survival in each
population.

II. To examine the frequency and severity of adverse events as assessed by CTCAE version 4
in each population.

III. To estimate the rate of objective tumor response in patients with measurable disease.
(09/04/12)

TERTIARY OBJECTIVES:

I. To explore whether immunohistochemical (IHC) expression of components of the mTOR
signaling pathway (PTEN, total and phosphorylated Akt, as well as, ABCC3 (MRP3), AB CF2,
cyclin E, and VEGF) are associated with outcome, nationality or clinical characteristics.

II. To explore whether there is any differences in differential gene expression profiles
between U.S. and worldwide (outside of Japan) versus Japanese patients.

OUTLINE: This is a multicenter study. Patients are stratified according to surgical extent
(optimal vs suboptimal).

Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30
minutes on day 1 and temsirolimus IV on days 1 and 8. Treatment repeats every 3 weeks for 6
courses. Patients then receive consolidation therapy comprising temsirolimus IV on days 1,
8, and 15. For circumstances in which docetaxel should be substituted for paclitaxel,
docetaxel will be given IV over 1 hour. Treatment repeats every 3 weeks for 11 courses in
the absence of disease progression or unacceptable toxicity. Patients may undergo sample
collection for exploratory studies.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.


Inclusion Criteria:



- Diagnosis of stage III or IV clear cell ovarian cancer

- Primary tumors must be ≥ 50% clear cell histomorphology*

- No primary peritoneal or fallopian tube carcinoma

- Negative for the expression of WT-1 antigen and estrogen receptor (ER) antigen by
IHC**

- Newly diagnosed disease

- Undergone initial surgery for the combined purpose of diagnosis, staging, and
cytoreduction within the past 2-12 weeks

- GOG performance status 0-2

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Total bilirubin normal

- AST ≤ 2.5 times upper limit of normal (ULN) (< 5 times ULN for patients with liver
metastases)

- Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN for patients with liver
metastases)

- Creatinine ≤ 1.5 times ULN

- Cholesterol ≤ 350 mg/dL (fasting)

- Triglycerides ≤ 400 mg/dL (fasting)

- Albumin ≥ 3.0 mg/dL

- PT such that INR is ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient
is on a stable dose of therapeutic warfarin for management of venous thrombosis
including pulmonary thrombo-embolus)

- PTT < 1.2 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study treatment

- Neurologic function (sensory and motor) ≤ CTCAE grade 1

- No severely impaired lung function, defined as a DLCO ≤ 50% of the normal predicted
value and/or oxygen saturation ≤ 88% at rest on room air

- No baseline requirement for oxygen

- None of the following:

- NYHA class III-IV symptomatic congestive heart failure

- Unstable angina pectoris

- Myocardial infarction within the past 6 months

- Serious uncontrolled cardiac arrhythmia

- Any other clinically significant disease

- No poorly controlled diabetes

- No active infection requiring antibiotics (except for uncomplicated urinary tract
infection)

- No active bleeding or pathologic conditions that carry high risk of bleeding, such as
known bleeding disorder, coagulopathy, or tumor involving major vessels

- No other invasive malignancies within the past 5 years except for nonmelanoma skin
cancer

- No other serious concurrent illness that, in the opinion of the treating physician,
will place the patient at unreasonable risk from study treatment

- No concurrent live vaccines

- No prior cancer treatment that contraindicates study therapy

- No prior treatment with a mTOR inhibitor (sirolimus, temsirolimus, everolimus),
paclitaxel, or carboplatin

- No prior radiotherapy to any portion of the abdominal cavity or the pelvis

- Prior radiotherapy for localized cancer of the breast, head and neck, or skin is
allowed provided that it was completed ≥ 5 years before registration and the
patient remains free of recurrent or metastatic disease

- No prior chemotherapy for any abdominal or pelvic tumor, including neoadjuvant
chemotherapy for the clear cell ovarian cancer

- No concurrent maintenance corticosteroids except for short-term (< 5 days) use

- No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine,
phenobarbital), any other CYP3A4 inducer (e.g., rifampin, St. John wort), or strong
CYP3A4 inhibitors

- No other concurrent investigational agents

- No concurrent sunitinib

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Progression-free survival

Outcome Description:

Will be characterized with Kaplan-Meier plots.

Outcome Time Frame:

12 months

Safety Issue:

No

Principal Investigator

John Farley

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02653

NCT ID:

NCT01196429

Start Date:

August 2010

Completion Date:

Related Keywords:

  • Ovarian Clear Cell Cystadenocarcinoma
  • Stage III Ovarian Epithelial Cancer
  • Stage IV Ovarian Epithelial Cancer
  • Cystadenocarcinoma
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms

Name

Location

Cleveland Clinic FoundationCleveland, Ohio  44195
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Abington Memorial HospitalAbington, Pennsylvania  19001
University of Washington Medical CenterSeattle, Washington  98195-6043
Tacoma General HospitalTacoma, Washington  98405
Hurley Medical CenterFlint, Michigan  48503
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Memorial Hospital of South BendSouth Bend, Indiana  46601
LDS HospitalSalt Lake City, Utah  84143
Rush University Medical CenterChicago, Illinois  60612-3824
University of Kansas Medical CenterKansas City, Kansas  66160-7353
Hartford HospitalHartford, Connecticut  06102-5037
Baystate Medical CenterSpringfield, Massachusetts  01199
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Group Health CooperativeSeattle, Washington  98112
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Winthrop University HospitalMineola, New York  11501
MetroHealth Medical CenterCleveland, Ohio  44109
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
McKay-Dee Hospital CenterOgden, Utah  84403
Cancer Care Northwest - Spokane SouthSpokane, Washington  99202
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Elkhart General HospitalElkhart, Indiana  46515
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Medical Oncology and Hematology AssociatesDes Moines, Iowa  50309
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Geisinger Medical GroupState College, Pennsylvania  16801
Wenatchee Valley Medical CenterWenatchee, Washington  98801-2028
Seattle Cancer Care AllianceSeattle, Washington  98109
Genesys Regional Medical CenterGrand Blanc, Michigan  48439-8066
Pacific Gynecology SpecialistsSeattle, Washington  98104
University of North CarolinaChapel Hill, North Carolina  27599
Duke University Medical CenterDurham, North Carolina  27710
Northwestern UniversityChicago, Illinois  60611
Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Case Western Reserve UniversityCleveland, Ohio  44106
Indiana University Medical CenterIndianapolis, Indiana  46202
Northwest HospitalSeattle, Washington  98133
Providence Saint Joseph Medical CenterBurbank, California  91505-4866
Florida HospitalOrlando, Florida  32803
Memorial Health University Medical CenterSavannah, Georgia  31404
Harrison Medical CenterBremerton, Washington  98310
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
M D Anderson Cancer CenterHouston, Texas  77030
University of Southern CaliforniaLos Angeles, California  90033
Northern Indiana Cancer Research ConsortiumSouth Bend, Indiana  
University of CincinnatiCincinnati, Ohio  45267-0502
Froedtert and the Medical College of WisconsinMilwaukee, Wisconsin  53226
Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
The Hospital of Central ConnecticutNew Britain, Connecticut  06050
Iowa Oncology Research Association CCOPDes Moines, Iowa  50309
Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des MoinesDes Moines, Iowa  50309
Michigan Cancer Research Consortium Community Clinical Oncology ProgramAnn Arbor, Michigan  48106
Oakwood HospitalDearborn, Michigan  48123
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Allegiance HealthJackson, Michigan  49201
Sparrow HospitalLansing, Michigan  48912
Saint Mary Mercy HospitalLivonia, Michigan  48154
Saint Joseph Mercy OaklandPontiac, Michigan  48341-2985
Saint Joseph Mercy Port HuronPort Huron, Michigan  48060
Saint Mary's of MichiganSaginaw, Michigan  48601
Lakeland HospitalSt. Joseph, Michigan  49085
Saint John Macomb-Oakland HospitalWarren, Michigan  48093
Ozark Health Ventures LLC dba Cancer Research for The Ozarks SpringfieldSpringfield, Missouri  65802
Saint John's HospitalSpringfield, Missouri  65804
Cox Medical CenterSpringfield, Missouri  65807
Cooper Hospital University Medical CenterCamden, New Jersey  08103
Kettering Medical CenterKettering, Ohio  45429
Geisinger Wyoming ValleyWilkes-Barre, Pennsylvania  18711
Harrison Bremerton Hematology and OncologyBremerton, Washington  98310
Swedish Medical Center-First HillSeattle, Washington  98122-4307
Saint Joseph Medical CenterTacoma, Washington  98405
Cancer Care Associates-YaleTulsa, Oklahoma  74136-1929
Women and Infants HospitalProvidence, Rhode Island  02905
Lake University Ireland Cancer CenterMentor, Ohio  44060
Stony Brook University Medical CenterStony Brook, New York  11794
Lahey Clinic Medical CenterBurlington, Massachusetts  01805
Elkhart ClinicElkhart, Indiana  46515
University of Colorado Cancer Center - Anschutz Cancer PavilionAurora, Colorado  80045
Michiana Hematology Oncology PC-ElkhartElkhart, Indiana  46514
Michiana Hematology Oncology PC-PlymouthPlymouth, Indiana  46563
Michiana Hematology Oncology PC-South BendSouth Bend, Indiana  46601
Michiana Hematology Oncology-PC WestvilleWestville, Indiana  46391
Michiana Hematology Oncology PC-NilesNiles, Michigan  49120
Utah Valley Regional Medical CenterProvo, Utah  84603
Dixie Medical Center Regional Cancer CenterSaint George, Utah  84770
Women's Cancer Center of NevadaLas Vegas, Nevada  89109
Central DuPage Hospital Cancer CenterWarrenville, Illinois  60555
Providence Regional Cancer PartnershipEverett, Washington  98201
Palo Alto Medical Foundation-Gynecologic OncologyMountain View, California  94040
Sudarshan K Sharma MD Limted-Gynecologic OncologyHinsdale, Illinois  60521
Saint Vincent Oncology CenterIndianapolis, Indiana  46260
PeaceHealth Medical Group PCBellingham, Washington  98226
Skagit Valley Hospital Regional Cancer Care CenterMount Vernon, Washington  98274
Olympic Medical Cancer Care CenterSequim, Washington  98384
Rockwood Cancer Treatment CenterSpokane, Washington  99204
Providence Saint Mary Regional Cancer CenterWalla Walla, Washington  99362
Michiana Hematology Oncology PC-MishawakaMishawaka, Indiana  46545-1470
Marie Yeager Cancer CenterSaint Joseph, Michigan  49085
Summa Akron City HospitalAkron, Ohio  44304
Gynecologic Oncology GroupPhiladelphia, Pennsylvania  19103
Geisinger Medical Center-Cancer Center HazeltonHazleton, Pennsylvania  18201
Community Howard Regional HealthKokomo, Indiana  46904
Indiana University Health La Porte HospitalLa Porte, Indiana  46350
Saint Joseph Regional Medical Center-MishawakaMishawaka, Indiana  46545-1470
Saint Joseph's Hospital and Medical CenterPhoenix, Arizona  85013
Harrison Poulsbo Hematology and OncologyPoulsbo, Washington  98370
Walter Reed Army Medical Center-OlneyOlney, Maryland  20832