Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Trastuzumab

Lapatinib

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Oral Pazopanib 200 mg every other day starting on day 1 and oral Lapatinib 500 mg daily starting day 1, both for 28 days.

Oral Pazopanib 200 mg daily for 28 day cycle and Trastuzumab (Herceptin®) 4 mg/kg loading dose as a 90 minute infusion by vein on day 1 of cycle 1, with a maintenance dose of 2 mg/kg every week as 30 minute infusion by vein.

Starting dose: 200 mg by mouth every other day starting on day 1 for 28 days.

Pazopanib

Starting dose 500 mg by mouth every day for 28 days.

4 mg/kg loading dose as a 90 minute infusion by vein on day 1 of cycle 1.

Maintenance dose of 2 mg/kg every week as 30 minute infusion by vein.

Dose Expansion Phase: Maximum tolerated dose (MTD) from Dose Escalation Phase

Trastuzumab (Herceptin®)

Starting dose 200 mg by mouth every day for 28 days.

David S. Hong, MD

The goal of this clinical research study is to find the highest tolerable dose of the combinations of pazopanib and either lapatinib or trastuzumab that can be given to patients with advanced cancer. The safety of the drug combinations will also be studied.

Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells.

Lapatinib is designed to prevent or slow down the growth of cancer cells by blocking 2 proteins on the surface of the cancer cell, which are HER 1 and HER 2 receptors.

Trastuzumab is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the Her2/neu receptor.

Study Groups:

If you are found to be eligible to take part in this study, your doctor will decide which study drugs you will receive based on the disease type and the drugs you have taken in the past

You will receive either a combination of pazopanib and lapatinib (Arm A) or a combination of pazopanib and trastuzumab (Arm B).

Up to 5 dose levels of each combination will be tested. Up to 6 participants will be enrolled at each dose level of each combination. The first group of participants will receive the lowest dose level of each combination. Each new group(s) will receive a higher combination than the group before it, if no intolerable side effects were seen. Participants may be enrolled on 1-3 similar dose levels at the same time. You will be assigned to a dose level based on when you joined this study. This will continue until the highest tolerable dose(s) of the study drug combination is found.

The dose of the study drug combination that you receive may be lowered if you have intolerable side effects.

Once the highest tolerable doses of the different combinations are found, this dose of each combination will be given to an expansion group of 20 extra participants.

Study Drug Administration:

If you are in Arm A, you will take lapatinib by mouth 1 time each day. You will take pazopanib by mouth 1 time every other day (Day 1, 3, 5, and so on). You should take pazopanib and lapatinib either 1 hour before or 2 hours after eating a meal.

If you are in Arm B, you will take pazopanib by mouth 1 time each day. You will receive trastuzumab by vein on Days 1, 8, 15, and 22 of each cycle. The first infusion will be over 90 minutes. If you handle the infusion well, the next infusions will be over 30 minutes. You should take pazopanib either 1 hour before or 2 hours after eating a meal.

Each study cycle is 28 days.

Study Visits:

At all study visits, you will be asked about any drugs you may be taking and side effects you may be having.

Week 3 of Cycle 1, blood (about 1 teaspoon) and urine will be collected for routine tests.

During Week 3 of Cycles 2 and beyond, blood (about 1 teaspoon) will be drawn for routine tests.

During Week 4 of Cycle 2 and then every 2-3 cycles:

* You will have a CT scan, MRI scan, PET scan, and/or x-ray to check the status of the disease.
* If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to measure tumor markers.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will be taken off study early if the disease gets worse, if you continue to have intolerable side effects, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the end-of-study visit.

End-of-Study Visit:

Within 30 days after your last dose of study drugs, you will have an end-of-study visit. At this visit, the following tests and procedures performed:

* Your medical history will be recorded.
* You will have a physical exam.
* You will be asked about any drugs you may be taking and side effects you may be having.
* Your weight, vital signs, and performance status will be recorded.
* Blood (about 2 teaspoons) and urine will be collected for routine tests.
* If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to measure tumor markers.
* If the study doctor thinks it is needed, you will have a chest x-ray, CT scan, MRI scan, and/or PET scan to check the status of the disease.

This is an investigational study. Pazopanib is FDA approved and commercially available for the treatment of renal cell carcinoma. Lapatinib and trastuzumab are FDA approved and commercially available for the treatment of breast cancer. The combination of pazopanib and lapatinib or pazopanib and trastuzumab is investigational.

Up to 174 participants will take part in this study. All will be enrolled at MD Anderson.

Pazopanib, Lapatinib or Trastuzumab in Subjects With Solid Tumors

Phase I Study of Pazopanib in Combination With Lapatinib or Trastuzumab in Subjects With Solid Tumors

MTD is defined as highest dose in which incidence of dose limiting toxicity (DLT) was less than 33% (approximately two or more participants in a dose cohort).

Computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, positron emission tomography (PET) scan, and/or x-ray to check the status of the disease. Tumor response calculated by Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization Working Group (WHO) criteria. A tumor response is defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by RECIST criteria, (3) decrease in tumor markers by more than or equal to 25% or (4) a partial response according to the Choi criteria.

M.D. Anderson Cancer Center

Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Disease Progression

Breast Diseases

Skin Diseases

Hormones

Anastrozole

Aromatase Inhibitors

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.

1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.

4mg/kg iv loading dose, followed by 2mg/kg iv weekly

trastuzumab (Herceptin®)

anastrazole (Arimidex®)

Clinical Trials

This 2 arm study assessed the safety and efficacy of adding intravenous trastuzumab (Herceptin®) to daily oral anastrozole (Arimidex®) tablets as first- and second-line treatment in postmenopausal patients with human epidermal growth factor receptor-2 (HER2) overexpressing metastatic breast cancer (ER+ve and/or PR+ve). Patients were randomized to receive either anastrazole 1 mg per os (po) daily, or anastrazole 1 mg po daily + a loading dose of Herceptin® 4 mg/kg intravenous (iv) followed by weekly doses of Herceptin® 2 mg/kg iv. The anticipated time on study treatment was until disease progression, and the target sample size was 100-500 individuals.

A Study to Evaluate the Efficacy and Safety of Herceptin® (Trastuzumab) in Combination With Arimidex® (Anastrozole) an Aromatase Inhibitor Compared to Arimidex® Alone in Patients With Metastatic Breast Cancer

A Randomized, Open-label Study of the Effect of Herceptin Plus Arimidex Compared With Arimidex Alone on Progression-free Survival in Patients With HER2-positive and Hormone-receptor Positive Metastatic Breast Cancer

PFS was assessed by the investigator based on World Health Organization (WHO) criteria using radiographic tumor evaluations. Disease progression was defined as the appearance of any new lesion not previously identified or an estimated increase of 25% or more in existent bidimensionally or unidimensionally measurable lesions or progression of an existing non-measurable lesion. For bidimensionally measurable malignant lesions with an area of at least 2.0 centimeters squared (cm\^2) an increase of 1.0 cm\^2 was required and for unidimensionally measurable lesions of 1.0 cm or less an increase of 0.5 cm was required. PFS was defined as the number of days between date of randomization and date of documented disease progression or date of death. Kaplan Meier estimates of PFS are presented.

Clinical Benefit was defined as stable disease for ≥ six months or complete response or partial response.

Duration of response was defined as the number of days from the day complete response or partial response was first noted to the day of progression of disease, death or last follow-up.

Time to response was defined as the number of days from the day of randomization to the day complete response or partial response was first noted.

Overall Survival is defined as the number of days from randomization to death.

Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Overall Response was defined as either complete response or partial response.

Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Best Response was defined as the best response a patient achieves in the study.

Participants rated their performance status using the ECOG Questionnaire on the following scale: 0=Fully active, perform all pre-disease activities without restriction; 1=Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature; 2=Ambulatory, capable of self-care, unable to carry out any work activities, up and about more than \>50% of waking hours; 3=Capable of limited self-care, confined to bed or chair \>50% of waking hours; 4=Completely disabled, not capable of any self-care, totally confined to bed or chair; 5=Dead.

The percentage of participants in the following categories:

Improved: Score decrease from baseline. Unchanged: Score the same as baseline. Worse: Score increase from baseline.

Number of participants with adverse events as a measure for safety as assessed by the collection of adverse events, laboratory tests for Hematology and Serum Chemistry, clinical assessments and cardiac monitoring.

Genentech, Inc.

Hoffmann-La Roche

Trastuzumab + Anastrozole

1 mg oral dose of anastrozole every day for 24 Months in the Main phase.

Anastrozole (After Start of Trastuzumab)

Total

Age Continuous

Sex: Female, Male

Medical Communications

24 Months

End of Study

Full analysis population included all randomized participants who received study drug.

Progression Free Survival (PFS)

Percentage of Participants With Clinical Benefit

Participants from the Full Analysis population (all randomized participants who received study drug) evaluable for response.

Duration of Response at 24 Months

Time to Response at 24 Months

Overall Survival at 24 Months

Full Analysis Population included all randomized participants who received study drug.

Percentage of Participants With Two-Year Survival

Participants from the Full Analysis Population (all randomized participants who received study drug) evaluable for response.

Percentage of Participants With Overall Tumor Response at 24 Months

Complete Response

Partial Response

Stable Disease

Progressive Disease

Response not assessed

Percentage of Participants With Best Tumor Response at 24 Months

Improved

No Change

Worse

Participants from the Full Analysis Population (includes all randomized participants who received study drug) with data available for analyses.

Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Final Visit Compared to Baseline

Duration of Response at End of Study

Time to Response at End of Study

Percentage of Participants With Overall Tumor Response at End of Study

Full Analysis Population includes all randomized participants who received study drug.

Percentage of Participants With Best Tumor Response at End of Study

Safety population included all participants who received at least one dose of study drug.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pazopanib, Lapatinib or Trastuzumab in Subjects With Solid Tumors	NCT01454804	Advanced Cancer...	Pazopanib Lapatinib Trastuzumab (He... Pazopanib	-	M.D. Anderson Cancer Center
A Study to Evaluate the Efficacy and Safety of Herceptin® (Trastuzumab) in Combination With Arimidex® (Anastrozole) an Aromatase Inhibitor Compared to Arimidex® Alone in Patients With Metastatic Breast Cancer	NCT00022672	Breast Cancer	trastuzumab (He... anastrazole (Ar...	18 Years -	Hoffmann-La Roche
Pazopanib, Lapatinib or Trastuzumab in Subjects With Solid Tumors	NCT01454804	Advanced Cancer...	Pazopanib Lapatinib Trastuzumab (He... Pazopanib	-	M.D. Anderson Cancer Center
A Study to Evaluate the Efficacy and Safety of Herceptin® (Trastuzumab) in Combination With Arimidex® (Anastrozole) an Aromatase Inhibitor Compared to Arimidex® Alone in Patients With Metastatic Breast Cancer	NCT00022672	Breast Cancer	trastuzumab (He... anastrazole (Ar...	18 Years -	Hoffmann-La Roche
Pazopanib, Lapatinib or Trastuzumab in Subjects With Solid Tumors	NCT01454804	Advanced Cancer...	Pazopanib Lapatinib Trastuzumab (He... Pazopanib	-	M.D. Anderson Cancer Center
Pazopanib, Lapatinib or Trastuzumab in Subjects With Solid Tumors	NCT01454804	Advanced Cancer...	Pazopanib Lapatinib Trastuzumab (He... Pazopanib	-	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for trastuzumab (herceptin®)