Ridaforolimus in Treating Patients With Recurrent Metastatic and/or Locally Advanced Endometrial Cancer

NCT00770185 | Completed Phase 2 DMC

• 4 other identifiers: I192CAN-NCIC-IND192ARIAD-CAN-NCIC-IND192CDR0000614597
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 11

Brief Summary

RATIONALE: Ridaforolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying the side effects of ridaforolimus and to see how well it works in treating patients with recurrent metastatic and/or locally advanced endometrial cancer.

Conditions

Endometrial Cancer

Keywords

endometrial adenocarcinoma; endometrial adenosquamous cell carcinoma; endometrial clear cell carcinoma; endometrial papillary carcinoma; recurrent endometrial carcinoma; stage III endometrial carcinoma; stage IV endometrial carcinoma

Outcome Measures

Primary Outcomes (4)

• Objective response measured by RECIST criteria

  After every second cycle

  every 8 weeks

• Adverse events

  Adverse events will be monitored and assessed from the time of the first dose with overall results being assessed at final analysis.

  4 years

• Time to progression

  4 years

• Correlation between objective tumor response with PTEN expression and other potential markers

  will be assessed overall at the time of completion of therapy and final analysis.

  4 years

Secondary Outcomes (1)

• Response duration

  4 years

Study Arms (1)

Ridaforolimus

EXPERIMENTAL

oral ridaforolimus 40 mg days 1-5 each week (once daily for 5 consecutive days every week; cycle arbitrarily defined as a 4 week period)

Drug: ridaforolimus; Genetic: gene expression analysis; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis

Interventions

ridaforolimus DRUG

oral ridaforolimus 40 mg days 1-5 each week (once daily for 5 consecutive days every week; cycle arbitrarily defined as a 4 week period)

Ridaforolimus

gene expression analysis GENETIC

Ridaforolimus

immunohistochemistry staining method OTHER

Ridaforolimus

laboratory biomarker analysis OTHER

Ridaforolimus

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed endometrial cancer, including any 1 of the following subtypes: * Adenocarcinoma * Papillary serous * Papillary * Villoglandular * Mucinous * Clear cell * Endometrioid * Adenosquamous carcinoma * Recurrent or metastatic and/or locally advanced disease * Incurable disease by standard therapies * Clinically and/or radiologically documented disease within the past 28 days (35 days if negative), defined as ≥ 1 unidimensionally measurable disease site meeting 1 of the following criteria: * At least 20 mm by x-ray or physical exam * At least 10 mm by spiral CT scan * At least 20 mm by non-spiral CT scan * Available tumor tissue (paraffin block or unstained slides) from primary tumor * No uterine sarcoma (leiomyosarcoma), mixed müllerian tumor (MMT), and/or adenosarcoma * No known brain metastases * Clinical suspicion of CNS involvement requires a head CT scan PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 12 weeks * Granulocyte count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Bilirubin ≤ upper limit of normal (ULN) * ALT and AST ≤ 2.5 times ULN * Creatinine ≤ 1.25 times ULN OR creatinine clearance ≥ 50 mL/min * Fasting serum cholesterol ≤ 9.0 mmol/L * Fasting triglycerides ≤ 4.56 mmol/L * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Accessible for treatment and follow up (e.g., 1 ½ hours driving distance from participating center) * No upper gastrointestinal or other condition that would impair swallowing or absorption of oral medication * No serious illness or medical condition that would not permit the patient to be managed according to the protocol, including, but not limited to, any of the following: * History of significant neurologic or psychiatric disorder (e.g., uncontrolled psychotic disorders) that would impair the ability to obtain consent or limit compliance with study requirements * Active uncontrolled or serious infection * Active peptic ulcer disease * Myocardial infarction within the past 6 months, congestive heart failure (even if medically controlled), unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, or uncontrolled hypertension * Pulmonary disease requiring oxygen * HIV infection or other immune deficiency * Other medical conditions that might be aggravated by study treatment * No history of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years * No known hypersensitivity to the study drug or its components PRIOR CONCURRENT THERAPY: * At least 7 days since prior hormonal therapy (progestational or aromatase inhibitor) as either adjuvant therapy or for treatment of metastatic disease * At least 21 days since prior major surgery and recovered * At least 28 days since prior radiotherapy and recovered * Prior low-dose palliative radiotherapy allowed * At least 4 months since prior adjuvant chemotherapy * No prior mTOR inhibitors * No prior or concurrent chemotherapy for metastatic or recurrent disease * More than 7 days since prior and no concurrent CYP3A4 inhibitors including, but not limited to, any of the following: * Azole antifungals (i.e., ketoconazole, itraconazole, miconazole, fluconazole) * HIV protease inhibitors (i.e., indinavir, saquinavir, ritonavir, atazanavir, nelfinavir) * Clarithromycin * Verapamil * Erythromycin * Delavirdine * Diltiazem * Nefazodone * Telithromycin * More than 12 days since prior and no concurrent CYP3A4 inducers including, but not limited to, any of the following: * Rifampin * Phenytoin * Rifabutin * St. John's wort * Carbamazepine * Efavirenz * Phenobarbital * Tipranavir * At least 14 days since prior and no concurrent investigational drugs or anticancer therapy (e.g., immunotherapy, biological response modifiers \[excluding hematopoietic growth factors\], and systemic hormonal therapy) * No concurrent CYP3A4 substrates

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• Ariad Pharmaceuticals: collaborator

Study Sites (11)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Related Publications (1)

• Tsoref D, Welch S, Lau S, Biagi J, Tonkin K, Martin LA, Ellard S, Ghatage P, Elit L, Mackay HJ, Allo G, Tsao MS, Kamel-Reid S, Eisenhauer EA, Oza AM. Phase II study of oral ridaforolimus in women with recurrent or metastatic endometrial cancer. Gynecol Oncol. 2014 Nov;135(2):184-9. doi: 10.1016/j.ygyno.2014.06.033. Epub 2014 Aug 28.

  PMID: 25173583 RESULT

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

ridaforolimus; Gene Expression Profiling; Immunohistochemistry

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

Intervention Hierarchy (Ancestors)

Genetic Techniques; Investigative Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Immunologic Techniques

Study Officials

• Amit M. Oza, MD

  Princess Margaret Hospital, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2008
• First Posted: October 9, 2008
• Study Start: November 13, 2008
• Primary Completion: March 19, 2012
• Study Completion: February 13, 2015
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (11)