Lapatinib and RAD-001 for HER2 Positive Metastatic Breast Cancer

NCT01283789 | Unknown Phase 2 DMC

• 1 other identifier: 12418
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

By doing this study, researchers hope to learn the effectiveness of the combination of Lapatinib and RAD-001 for treating patients who have progressed on previous therapies.

Conditions

Metastatic Breast Cancer

Keywords

breast; cancer; metastatic; metastasis

Outcome Measures

Primary Outcomes (1)

• Assess the effectiveness of the combination of RAD-001 and lapatinib

  To assess the effectiveness of the combination of RAD-001 and lapatinib as measured by the six-month Overall Response Rate in women with MBC who have progressed on trastuzumab and/or lapatinib based therapies.

  6 months

Secondary Outcomes (1)

• Overall benefit of combination

  6 months

Study Arms (1)

Lapatinib and RAD-001

EXPERIMENTAL

RAD-001 will be administered orally as a once-daily dose of 5 mg (one 5 mg tablet) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD-001 in the morning, at the same time each day. Lapatinib will be administered orally as a once-daily dose of 1250 mg (five 250 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take lapatinib at bedtime, at the same time each day. Lapatinib should be taken by the patient in a fasting state.

Drug: Lapatinib and RAD-001

Interventions

Lapatinib and RAD-001 DRUG

Lapatinib will be taken orally as a once-daily dose of 1250 mg (five 250 mg tablets) continuously from study day 1 until progression of disease. Patients will take the tablet at bedtime, at the same time each day, in a fasting state. Everolimus will be taken orally as a once-daily dose of 5 mg (one 5 mg tablet) from study day 1 until progression of disease. Patients will take the tablet at the same time each morning.

Also known as: everolimus, tykerb

Lapatinib and RAD-001

Eligibility Criteria

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

You may qualify if:

• Females \> 18 years of age
• Histologically proven adenocarcinoma of breast in primary or metastatic setting. Stage: Locally advanced (inoperable) or metastatic
• HER2 positive breast cancer (IHC 3+ or FISH ratio of \> 2.0)
• ECOG Performance status 0-2
• Up to four prior chemotherapy regimens and anti-HER2 agents in metastatic setting allowed. Must have progressed on at least one HER2 targeted therapy (lapatinib or Herceptin) for metastatic breast cancer.
• Women of childbearing potential must have negative urine or serum pregnancy test within 7 days prior to administration of Everolimus. If barrier contraceptives are used, they must be continued throughout trial by both sexes. Hormonal contraceptives not acceptable as a sole method of contraception.
• Adequate kidney function: serum creatinine of \< 1.5 mg/dl and/or creatinine clearance of \> 60 mL/min
• Adequate hepatic function: transaminases \< 2.5 x upper limit of normal (up to 5 x ULN in patients with liver metastases) and total bilirubin \< 1.5 mg/dL. Adequate coagulation: INR ≤ 2.0 and PTT \< 1.5 X the upper limit of institution normal range. Oral anticoagulants, eg, warfarin are CYP2C9 substrates and, as such, no interaction with Everolimus is expected. Anticoagulation with Coumadin is allowed if target INR is ≤ 2.0 and stable for \> 2weeks. Anticoagulation with LMW is allowed.
• Must be informed of investigational nature of study, and must sign an informed consent
• Pretreatment lab values (must be performed within 14 days of patient registration unless otherwise specified. Other baseline studies must be performed within 30 days of registration.
• Patients will have baseline CT chest, abdomen and pelvis within 30 days of registration.
• Adequate cardiac function (LVEF ≥ 50% as measured by echocardiogram or MUGA scan).
• 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, patient may be included after initiation of appropriate lipid lowering medication with approval from the principal investigator.
• Must have measurable or non-measurable disease by RECIST criteria (version 1.1), with radiologic scans performed within 30 days of registration. Baseline scans can include:
• CT Scan or MRI and Bone Scan OR

You may not qualify if:

• Patients who have received prior lapatinib for metatastic breast cancer will be excluded.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics or psychiatric illness/social situations that would limit compliance with study requirements.
• GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (eg, Crohn's, ulcerative colitis).
• Current active hepatic or biliary disease (exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• Pregnant and lactating women. Women of reproductive potential not using or unwilling to use effective birth control methods throughout the trial.
• Severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study such as:
• Symptomatic congestive heart failure of NYHA 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
• liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C). 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 PCR testing required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.
• Patients with symptomatic brain metastases who have not completed radiation therapy and/or are receiving systemic steroid therapy. Patients with leptomeningeal disease will be excluded.
• Patients with CNS progression during the trial will be allowed to receive local treatment for CNS metastases and will remain on protocol. Trial medications will be held during hte time patients are receiving radiation therapy as dictated by their treating physicians.
• Patients receiving chronic, systemic treatment with corticosteroids (of more than 4mg/day or equivalent of dexamethasone. Doses of dexamethasone of up to 8mg/day may be administered for less than 2 weeks) or another immunosuppressive agent. 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.
• Severely impaired lung function 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.

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• Novartis: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

University of Kansas Medical Centner

Kansas City, Kansas, 66160, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms; Neoplasm Metastasis

Interventions

Lapatinib; Everolimus

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Qamar Khan, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

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: January 10, 2011
• First Posted: January 26, 2011
• Study Start: February 1, 2011
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2017
• Last Updated: February 8, 2017

Record last verified: 2017-02

Locations

US (1)