Temsirolimus With or Without Megestrol and Tamoxifen in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00729586
First received: August 6, 2008
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

This randomized phase II trial is studying temsirolimus to see how well it works with or without megestrol and tamoxifen in treating patients with advanced, persistent, or recurrent endometrial cancer. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of endometrial cancer cells. Hormone therapy using megestrol and tamoxifen may fight endometrial cancer by blocking the use of estrogen by the tumor cells. It is not yet known whether temsirolimus is more effective when given alone or together with megestrol and tamoxifen in treating endometrial cancer.


Condition Intervention Phase
Recurrent Endometrial Carcinoma
Stage III Endometrial Carcinoma
Stage IV Endometrial Carcinoma
Drug: megestrol acetate
Drug: tamoxifen citrate
Drug: temsirolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Temsirolimus (NCI-Supplied Agent, NSC # 683864, IND # 61010) or the Combination of Hormonal Therapy Plus Temsirolimus in Women With Advanced, Persistent, or Recurrent Endometrial Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Frequency of complete and partial clinical response, measured using GOG RECIST Criteria [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Survival time [ Time Frame: From entry into the study to death or the date of last contact, assessed up to 1 year ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: From study entry until disease progression, death or date of last contact, assessed up to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease that occurs in a patient administered a medical treatment, whether the event is considered related [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Graded according to the CTCAE version 3.0. The frequency and severity of all toxicities will be tabulated.


Estimated Enrollment: 84
Study Start Date: September 2008
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive temsirolimus IV over 30 minutes once weekly for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
Experimental: Arm II (closed to accrual as of 12/21/09)
Patients receive temsirolimus as in arm I. Patients also receive oral megestrol acetate twice daily for 3 weeks alternating with oral tamoxifen citrate twice daily for 3 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Drug: megestrol acetate
Given orally
Other Names:
  • BDH 1298
  • Maygace
  • Megace
  • Megestil
  • Niagestin
Drug: tamoxifen citrate
Given orally
Other Names:
  • Nolvadex
  • TAM
  • tamoxifen
  • TMX
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the response rate in patients with advanced, persistent, or recurrent endometrial carcinoma treated with temsirolimus with or without hormonal therapy comprising megestrol acetate and tamoxifen citrate.

II. To determine the time to progression and number of patients remaining on study therapy at 24 weeks.

SECONDARY OBJECTIVE:

III. To describe the toxicities of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prior treatment for endometrial carcinoma (adjuvant chemotherapy or chemoradiotherapy at the time of initial diagnosis or for a pelvic recurrence vs no adjuvant chemotherapy or chemoradiotherapy at the time of initial diagnosis or for a pelvic recurrence). Patients are randomized to 1 of 2 treatment arms (arm II closed to accrual as of 12/21/09).

ARM I: Patients receive temsirolimus IV over 30 minutes once weekly for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

ARM II (closed to accrual as of 12/21/09): Patients receive temsirolimus as in arm I. Patients also receive oral megestrol acetate twice daily for 3 weeks alternating with oral tamoxifen citrate twice daily for 3 weeks.

Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 1 year.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically* confirmed endometrial carcinoma

    • NOTE: *Histologic documentation of recurrence is not required
    • Advanced (FIGO stage III or IV), persistent, or recurrent disease that cannot be cured by surgery or radiotherapy
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (e.g., palpation, plain x-ray, CT scan, and MRI) or ≥ 10 mm by spiral CT scan
  • Must have at least one "target lesion" to be used to assess response, as defined by RECIST criteria

    • Tumors within a previouslyirradiated field will be designated as "non-target" lesions unless progression isdocumented
  • No sarcoma, carcinosarcoma, or leiomyosarcoma of the uterine corpus
  • GOG performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelet count ≥ 100,000/mcL
  • 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
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception
  • Able to take oral medication
  • No known congestive heart failure
  • No baseline requirement for oxygen
  • No history of unprovoked deep vein thrombosis or pulmonary embolism, unless patient is maintained on anticoagulation for the duration of the study
  • No concurrent serious illness that, in the opinion of the treating physician, would place the patient at unreasonable risk from study therapy
  • No other invasive malignancy within the past 5 years, except non-melanoma skin cancer
  • At least 4 weeks since prior major surgery (e.g, hysterectomy or resection of a lung nodule)
  • At least 4 weeks since minor surgery (e.g., port-a-cath placement)
  • No more than 1 prior chemotherapy regimen (including chemoradiotherapy)

    • No prior chemotherapy for stage IV disease, except in the case where the patient was without evidence of disease at the completion of chemotherapy and had at least 6 months of progression-free survival since the completion of chemotherapy
    • Prior chemoradiotherapy for a pelvic recurrence is allowed
    • Prior chemotherapy in the adjuvant setting for stage I, II, or III disease is allowed
    • No prior chemotherapy for metastatic or recurrent disease except as noted above
  • No prior hormonal or biologic therapy for endometrial carcinoma
  • No prior cancer treatment that would contraindicate study therapy
  • No concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (e.g., phenytoin, carbamazepine, or phenobarbital) or any other CYP3A4 inducer (e.g., rifampin or St. John's wort)
  • No concurrent maintenance corticosteroids, except for short-term use (i.e., < 5 days)
  • No concurrent prophylactic granulocyte colony-stimulating factors

    • Concurrent granulocyte colony-stimulating factors for neutropenic fever allowed
  • No concurrent oral contraceptives
  • No other concurrent investigational agents
  • No other concurrent anticancer therapies
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00729586

  Show 112 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Gini Fleming Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00729586     History of Changes
Other Study ID Numbers: NCI-2009-01085, NCI-2009-01085, GOG-0248, CDR0000609740, GOG-0248, GOG-0248, U10CA027469
Study First Received: August 6, 2008
Last Updated: December 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Endometrial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Carcinoma
Uterine Diseases
Genital Diseases, Female
Megestrol
Megestrol Acetate
Tamoxifen
Sirolimus
Everolimus
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Appetite Stimulants
Central Nervous System Stimulants
Central Nervous System Agents
Selective Estrogen Receptor Modulators

ClinicalTrials.gov processed this record on April 14, 2014