Single Arm Trial With Combination of Everolimus and Letrozole in Treatment of Platinum Resistant Relapse or Refractory or Persistent Ovarian Cancer/Endometrial Cancer

NCT02188550 | Unknown Phase 2

• 1 other identifier: CRAD001CUS242T
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine if the combination of Everolimus and Letrozole is effective in the treatment of women with either recurrent or persistent epithelial ovarian, fallopian tube, primary peritoneal or endometrial cancer. Experiments have shown that everolimus (Afinitor®) can prevent cells such as cancer from growing in number. Therefore, everolimus (Afinitor®) is being tested in specific diseases to stop cells from growing too fast (as in cancer). Everolimus (Afinitor®) has been FDA approved for adults with advanced kidney cancer (Renal Cell Carcinoma). Everolimus (Afinitor®) received approval for patients with subependymal giant cell astrocytoma (SEGA), a brain tumor seen with genetic conditions called tuberous sclerosis complex (TSC) who require therapy, but are not candidates for surgery. Everolimus (Afinitor®) was approved for pancreatic neuroendocrine tumor (PNET) in patients with unresectable, locally advanced, or metastatic disease. Everolimus (Afinitor®) received approval for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2- negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole. Everolimus (Afinitor®) also received approval for the treatment of patients with TSC who have renal angiomyolipoma not requiring immediate surgery. Everolimus (Afinitor®) has been used to treat patients in clinical studies since 2002 and approximately 25,645 patients (as of 30-Sep-2012) have been treated with everolimus (Afinitor®).

Conditions

Ovarian Cancer; Endometrial Cancer

Keywords

relapse or refractory or persistent epithelial ovarian fallopian tube; primary peritoneal carcinoma or endometrial cancer

Outcome Measures

Primary Outcomes (1)

• Tumor Response to treatment with Everolimus and Letrozole using RECIST Criteria

  The duration of response will be documented and also compared to the duration of response ot the last, most recent, cancer treatment.

  Baseline, Then every 12 weeks while on Everolimus and Letrozole up to 36 months

Secondary Outcomes (1)

• Overall survival of patients treated with the combination of letrozole and everolimus

  From randomization until date of death, assessed up to 36 months

Study Arms (1)

Single

EXPERIMENTAL

This is a single arm, non-randomized, open-label study with a combination of everolimus and letrozole once a day dosing . Each cycle would be 28days and patients would be scanned after every 3 cycles for response, until disease progression is documented

Drug: everolimus and letrozole

Interventions

everolimus and letrozole DRUG

This is a single arm, non-randomized, open-label study with a combination of everolimus and letrozole once a day dosing . Each cycle would be 28days and patients would be scanned after every 3 cycles for response, until disease progression is documented The duration of the study will be until disease progression Everolimus and Letrozole will be administered as noted below; 6.1.1 Dosing regimen Dosage : Everolimus Dose: 10 Unit: mg Frequency: daily Route of administration: Orally Dosage : Letrozole Dose: 2.5 Unit: mg Frequency: daily Route of administration: Orally

Single

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Post-menopausal or post-oophorectomy.
• Performance status Less than or equal to ECOG 2
• Patients must have relapse or refractory or persistent epithelial ovarian, fallopian tube, primary peritoneal carcinoma or endometrial cancer. Histologic documentation of the original primary tumor is required via pathology report.
• Patients must have received treatment with a platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin. This initial treatment may have included intraperitoneal therapy, consolidation, noncytotoxic agents (biologic/targeted therapy) or extended therapy administered after surgical or non-surgical assessment.
• Patients must have platinum-resistant disease, defined as progression \< 12 months after completion of first-or-second-line platinum based chemotherapy. The date (platinum-free interval) should be calculated from the last administered dose of platinum therapy.
• Platinum sensitive patients must have progressed/relapsed after receiving a second line platinum therapy.
• Patients with platinum-refractory primary disease, defined as having disease3 progression while receiving first-line platinum-based chemotherapy.
• Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of relapse or refractory or persistent disease.
• Patients are allowed to have received, but are not required to have received, biologic/targeted therapy (e.g., bevacizumab and/or PARP inhibitor) as part of their primary treatment regimen or for management of relapse or refractory or persistent disease.

You may not qualify if:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of Everolimus (including chemotherapy, antibody based therapy, etc.); radiation therapy within 2 weeks.
• Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g.
• sirolimus, temsirolimus) or to Letrozole.
• Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus;
• Patients who have any severe and/or uncontrolled medical conditions such as:
• unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to start of Everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
• Symptomatic congestive heart failure of New York heart Association Class III or IV
• active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active or chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA),
• known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air),
• active, bleeding diathesis;
• Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are allowed;

Sponsors & Collaborators

• Sinai Hospital of Baltimore: lead

Study Sites (1)

Sinai Hospital of Baltimore, Inc.

Baltimore, Maryland, 21215, United States

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms; Recurrence

Interventions

Everolimus; Letrozole

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: May 9, 2014
• First Posted: July 11, 2014
• Study Start: June 1, 2014
• Primary Completion: June 1, 2016
• Last Updated: May 19, 2015

Record last verified: 2015-05

Locations

US (1)