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Clinical Trials (PDQ®)

Temsirolimus, Carboplatin, and Paclitaxel as First-Line Therapy in Treating Patients With Newly Diagnosed Stage III-IV Clear Cell Ovarian Cancer

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and overNCINCI-2011-02653
CDR0000684262, GOG-0268, U10CA027469, NCT01196429

Trial Description

Summary

This phase II trial studies how well temsirolimus, carboplatin, and paclitaxel as first-line therapy works in treating patients with newly diagnosed stage III-IV clear cell ovarian cancer. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus with combination chemotherapy may be an effective treatment for ovarian cancer.

Further Study Information

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 United States (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 Common Terminology Criteria for Adverse Events (CTCAE) version 4 in each population.

III. To estimate the rate of objective tumor response in patients with measurable disease.

TERTIARY OBJECTIVES:

I. To explore whether immunohistochemical (IHC) expression of components of the mammalian target of rapamycin (mTOR) signaling pathway (phosphatase and tensin homolog [PTEN], total and phosphorylated protein kinase B [Akt], as well as, ATP-binding cassette, sub-family C [CFTR/MRP], member 3 [ABCC3] [MRP3], ATPase, H+ transporting, lysosomal accessory protein 1 [AB CF2], cyclin E, and vascular endothelial growth factor [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:

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. Treatment repeats every 3 weeks for 11 courses in the absence of disease progression or unacceptable toxicity.

NOTE: * For circumstances in which docetaxel should be substituted for paclitaxel, docetaxel is given IV over 1 hour.

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

Eligibility Criteria

Inclusion Criteria:

  • Patients must have stage III or IV clear cell ovarian cancer; primary tumors must be at least 50% clear cell histomorphology in order to be eligible; in addition, the tumors should be negative for expression of Wilms tumor 1 (WT-1) antigen and estrogen receptor (ER) antigen by immunohistochemistry; appropriate tissue sections to confirm stage and histologic classification of cell type must be sent to Gynecologic Oncology Group (GOG) for central pathology review; immunohistochemical stained slides for ER and WT-1 antigen must be also be submitted to GOG for pathology review
  • Patients who have met the pre-entry requirements
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information
  • Patients with a GOG performance status of 0, 1, or 2
  • Patients must be entered between 2 and 12 weeks after initial surgery; performed for the combined purpose of diagnosis, staging and cytoreduction
  • Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
  • Absolute neutrophil count >= 1,500/mcl
  • Platelets >= 100,000/mcl
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 times institutional upper limit of normal (< 5 times upper limit of normal [ULN] for subjects with liver metastases)
  • Alkaline phosphatase =< 2.5 times institutional upper limit of normal (< 5 times ULN for subjects with liver metastases)
  • Creatinine =< 1.5 x institutional upper limit of normal, grade 1 per CTCAE v. 4.0
  • Cholesterol =< 350 mg/dL (fasting)
  • Triglycerides =< 400 mg/dL (fasting)
  • Albumin >= 3.0 g/dL
  • Prothrombin time (PT) such that international normalized ratio (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)
  • Partial thromboplastin time (PTT) < 1.2 times the upper limit of normal
  • Neurologic function (sensory and motor) =< CTCAE grade 1

Exclusion Criteria:

  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
  • Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than five years prior to registration, and the patient remains free of recurrent or metastatic disease
  • Patients who have received prior chemotherapy for any abdominal or pelvic tumor including neo-adjuvant chemotherapy for their clear cell ovarian cancer
  • Patients with primary peritoneal and fallopian tube carcinoma are not eligible
  • Previous treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus), paclitaxel, or carboplatin
  • Patients cannot be receiving enzyme-inducing antiepileptic drugs (enzyme-inducing antiepileptic drugs [EIAEDs]; e.g., phenytoin, carbamazepine, phenobarbital) nor any other cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin or St. John's Wort; use of agents that potently inhibit CYP3A4 (and hence may raise temsirolimus levels), such as ketoconazole, is discouraged, but not specifically prohibited; the appropriateness of use of such agents is left to physician discretion; strong CYP3A4 inhibitors are prohibited
  • Patients receiving any investigational agents
  • Patients with severely impaired lung function defined as a diffusion lung capacity for carbon monoxide (DLCO) =< 50% of the normal predicted value and/or oxygen (O2) saturation =< 88% at rest on room air
  • Patients with symptomatic congestive heart failure of New York Heart Association class III or IV, unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant disease
  • Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
  • Patients on maintenance corticosteroids are ineligible with the exception of short term use (fewer than 5 days)
  • Patients with baseline requirement for oxygen
  • Patients with serious concomitant illness which, in the opinion of the treating physician, will place patient at unreasonable risk from therapy on this protocol
  • Patients who are pregnant or nursing; patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of study therapies
  • Patients with poorly controlled diabetes

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

John FarleyPrincipal Investigator

Trial Sites

U.S.A.
Kansas
  Kansas City
 Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
 Julia A. Chapman Ph: 913-588-4709
Maryland
  Olney
 Walter Reed Army Medical Center-Olney
 Sarah Bernstein Ph: 202-782-3559
  Email: sarah.bernstein@med.navy.mil
Massachusetts
  Boston
 Massachusetts General Hospital
 Michael J Birrer Ph: 617-726-8624
  Email: mbirrer@partners.org
  Springfield
 Baystate Medical Center
 Tashanna K Myers Ph: 413-794-3565
  Email: tamara.wrenn@baystatehealth.org
Ohio
  Columbus
 Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
 John H Farley
Texas
  Houston
 M. D. Anderson Cancer Center at University of Texas
 Jubilee Brown
  Email: jbbrown@mdanderson.org
Japan
  Minato-ku, Tokyo
 Jikei University School of Medicine
 Kyosuke Yamada Ph:  03-3433-1111 ext 2153
  Tottori
 Tottori University Hospital
 Junzo Kigawa Ph: 0857-31-5007
Aoba-ku
  Sendai
 Tohoku University Graduate School of Medicine
 Nobuo Yaegashi
  Email: med-som@bureau.tohoku.ac.jp
Hiroshima
  Kure
 National Hospital Organization - Medical Center of Kure
 Kazuhiro Takehara Ph: 089-999-1172
Iwate
  Morioka
 Iwate Medical University Hospital
 Toru Sugiyama Ph: 019-651-5111
Niigata
  Niigata City
 Niigata University Medical and Dental Hospital
 John H Farley

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01196429
ClinicalTrials.gov processed this data on June 24, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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