A Study of Combination of Temsirolimus (Torisel®) and Pegylated Liposomal Doxorubicin (PLD, Doxil®/Caelyx®) in Advanced or Recurrent Breast, Endometrial and Ovarian Cancer

NCT00982631 | Unknown Phase 1 DMC

• 1 other identifier: UMCNONCO200902
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A study to examine the combination of temsirolimus and Caelyx® (chemotherapeutic) in advanced or recurrent breast, endometrial and ovarian cancer.

Conditions

Advanced/Recurrent Breast Cancer; Endometrial Cancer; Ovarian Cancer

Keywords

temsirolimus (Torisel®); pegylated liposomal doxorubicin (PLD, Doxil®/ Caelyx®)

Outcome Measures

Primary Outcomes (1)

• MTD, pharmacokinetic parameters

  2 years

Secondary Outcomes (1)

• Effectiveness: objective response rate, time to progression

  2 years

Study Arms (1)

temsirolimus/PLD

EXPERIMENTAL

temsirolimus (Torisel) with pegylated liposomal doxorubicin (PLD,Doxil,Caelyx);a dose escalating study in a 3+3 design

Drug: Temsirolimus/PLD

Interventions

Temsirolimus/PLD DRUG

This is a dose escalation study. Patients will start with temsirolimus iv once weekly. After 2 weeks, PLD therapy is added. From then on, PLD is repeated every 4 weeks. One cycle is 28 days. The DLT period is also defined within the first 28 days of combination therapy (thus the first 6 weeks of study participation). The first dose level (DL) is DL 1. Depending on toxicity, intermediate dose levels can be added. If no MTD is found in the sixth cohort, this dose level will be considered as the recommended dose (RD), being the optimal dose for both drugs in this combination. At the MTD dose level, the dose level will be expanded to a total of 12 patients.

temsirolimus/PLD

Eligibility Criteria

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

You may qualify if:

• Patients with proven advanced breast cancer, endometrial cancer or ovarian cancer, who are refractory to standard therapies or for whom no standard therapy exists.
• Age ≥ 18 years
• Patients who have an ECOG status of 0 or 1
• Patients who have a life expectancy of at least 12 weeks
• Negative pregnancy test for female patients of childbearing potential
• Signed informed consent

You may not qualify if:

• Adequate bone marrow: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and haemoglobin ≥ 5.0 mmol/l
• Adequate renal function: GFR ≥ 60 ml/min
• Adequate liver function: ALT and AST \< 2.5 x ULN, total bilirubin ≤ 1x ULN
• Fasting level of total cholesterol of no more than 350 mg/dL (9.1 mmol/L) and triglyceride level of no more than 400 mg/L (4.5 mmol/L)
• Left ventricular ejection fraction (LVEF) \< 50%
• History of serious cardiac disease
• Active clinically serious bacterial, viral or fungal infections (\> grade 2).
• Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
• Clinically symptomatic brain or meningeal metastasis. Patients with seizure disorders requiring medication (such as steroids or antiepileptics). Concomitant treatment with strong CYP3A4 inductors (such as rifampicin, St. John´s Wort) or CYP3A4 inhibitors (such as ketoconazole, voriconazole, itraconazole, diltiazem, verapamil, erythromycin) within 2 weeks prior to start.
• Moderate or weak CYP3A4 modifiers should be used concomitantly only after careful assessment of risk-benefit ratio. Concomitant use of carbamazepine, phenobarbital, phenytoin or chronic use of dexamethasone is not allowed. (Table 1)
• Other concomitant anti-cancer therapy (except steroids)
• Concomitant use of streptozocin, mercaptopurine.
• Previous treatment with one of the study drugs.
• Previous treatment with other mTOR inhibitors
• Prior investigational therapy/agents within 4 weeks of start, in case of bevacizumab at least 60 days between bevacizumab discontinuation and first dosing of temsirolimus.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

University Medical Center Nijmegen st Radboud

Nijmegen, Gelderland, 6525 GH, Netherlands

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Endometrial Neoplasms; Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• C.M.L. van Herpen, MD, Phd

  UMCN st Radboud

  PRINCIPAL INVESTIGATOR

Central Study Contacts

C.M.L. van Herpen, Md, Phd

CONTACT

+31 24 3610353; c.vanherpen@onco.umcn.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2009
• First Posted: September 23, 2009
• Study Start: June 1, 2009
• Primary Completion: February 1, 2012
• Study Completion: August 1, 2012
• Last Updated: April 11, 2012

Record last verified: 2012-04

Locations

NL (1)