RAD001 Plus Carboplatin in Breast Cancer Patients

NCT01127763 | Completed Phase 2 Results DMC

• 1 other identifier: NYU 09-0060
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates the effectiveness of combination of carboplatin and investigational agent RAD001 in triple-negative breast cancer.

Conditions

Breast Cancer

Keywords

metastatic; breast; cancer

Outcome Measures

Primary Outcomes (3)

• Clinical Benefit Rate (Complete Response, Partial Response, and Stable Disease That Lasts More Than 6 Months)

  Clinical benefit rate is defined as the number of patients with complete response (CR), partial response (PR), or stable disease (SD) that lasts at least 6 months. Response was assessed every 2 cycles of treatment (6 weeks) by computed tomography (CT), CT/positron emission tomography (PET), or magnetic resonance imaging (MRI). Overall response evaluation is based on Response Evaluation Criteria In Solid Tumors 1.0 (RECIST 1.0). Per RECIST 1.0 for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  up to 1 year

• Toxicity Profile-Hematological

  Reported as percentage of patients who experienced grade 3 and higher hematological adverse events (AEs) related to the study drugs.

  treatment period (up to 1 year) plus 30 days off treatment

• Toxicity Profile-Non Hematological

  Reported as percentage of patients who experienced grade 3 and higher non-hematological AEs related to the study drugs.

  treatment period (up to 1 year) plus 30 days off treatment

Secondary Outcomes (1)

• Median Progression-free Survival Time

  up to 1 year

Study Arms (1)

RAD001+carboplatin

EXPERIMENTAL

Carboplatin (starting dose was initially AUC 6, later decreased to AUC 5, then AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day until disease progression or unacceptable toxicity.

Drug: RAD001; Drug: Carboplatin

Interventions

RAD001 DRUG

Also known as: Afinitor, Everolimus

RAD001+carboplatin

Carboplatin DRUG

Also known as: Paraplatin

RAD001+carboplatin

Eligibility Criteria

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

You may qualify if:

• Women with metastatic breast cancer (measurable or evaluable including bone metastases only)
• Histologically confirmed triple negative breast cancer (estrogen receptor (ER)\< 10%, progesterone receptor (PR) \< 10 %, Her2neu IHC 0 or 1 or FISH negative)
• Age \>= 18 years
• World Health Organization performance status \<= 2
• Adequate bone marrow function as shown by: absolute neutrophil count ≥ 1.5 x 10\^9/L, Platelets ≥ 100 x 10\^9/L, Hb \>9 g/dL
• Adequate liver function as shown by:
• serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
• international normalized ratio (INR): Patients not on warfarin INR ≤1.5; Patients on warfarin INR ≤3; Patient on stable dose of low molecular weight heparin for \>2 weeks at time of treatment is allowed.
• alanine aminotransferase and aspartate aminotransferase ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases)
• Adequate renal function: serum creatinine ≤ 1.5 x ULN
• Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
• Signed informed consent
• Patients may have had 0-3 prior regimens for metastatic disease and prior bevacizumab (avastin) is allowed.
• A baseline lung CT (or PET/CT)
• O2 sat \>= 90% in room air (if \<90%, spirometry and diffusion capacity of lung for carbon monoxide (DLCO) above 50% of the normal predicted value of pulmonary function tests)

You may not qualify if:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks of the start of study drug (including chemotherapy, radiation therapy, and biologics)
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• Prior treatment with any investigational drug within the preceding 2 weeks
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. However, patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with RAD001. Topical or inhaled corticosteroids are allowed.
• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Symptomatic congestive heart failure of New York heart Association Class III or IV
• unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
• severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
• uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN
• active (acute or chronic) or uncontrolled severe infections
• liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis. Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA polymerase chain reaction testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.
• A known history of HIV seropositivity

Sponsors & Collaborators

• NYU Langone Health: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

NYU Clinical Cancer Center

New York, New York, 10016, United States

Location

Related Publications (1)

• Singh J, Novik Y, Stein S, Volm M, Meyers M, Smith J, Omene C, Speyer J, Schneider R, Jhaveri K, Formenti S, Kyriakou V, Joseph B, Goldberg JD, Li X, Adams S, Tiersten A. Phase 2 trial of everolimus and carboplatin combination in patients with triple negative metastatic breast cancer. Breast Cancer Res. 2014 Mar 31;16(2):R32. doi: 10.1186/bcr3634.

  PMID: 24684785 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Neoplasms

Interventions

Everolimus; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Coordination Complexes

Results Point of Contact

• Title: Amy Tiersten, MD
• Organization: Mt Sinai School of Medicine

amy.tiersten@mssm.edu

212-249-3300

Study Officials

• Amy Tiersten, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: May 19, 2010
• First Posted: May 21, 2010
• Study Start: June 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: March 1, 2013
• Last Updated: April 9, 2014
• Results First Posted: April 9, 2014

Record last verified: 2014-03

Locations

US (1)