NCT01454804

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
43

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Oct 2011

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2011

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

October 12, 2011

Completed
7 days until next milestone

First Posted

Study publicly available on registry

October 19, 2011

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
Last Updated

April 13, 2016

Status Verified

March 1, 2015

Enrollment Period

3.4 years

First QC Date

October 12, 2011

Last Update Submit

April 11, 2016

Conditions

Advanced Cancers

Keywords

Advanced CancersSolid TumorsPazopanibGW786034LapatinibTykerbGW572016TrastuzumabHerceptin

Outcome Measures

Primary Outcomes (2)

  • Maximum Tolerated Dose (MTD) of Pazopanib in Combination with Lapatinib or Trastuzumab

    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).

    28 day cycle

  • Tumor Response

    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.

    End of second 28 day cycle

Study Arms (2)

Arm A: Pazopanib + Lapatinib

EXPERIMENTAL

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

Drug: PazopanibDrug: Lapatinib

Arm B: Pazopanib + Trastuzumab

EXPERIMENTAL

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.

Drug: Trastuzumab (Herceptin®)Drug: Pazopanib

Interventions

PazopanibDRUG

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

Also known as: GW78634
Arm A: Pazopanib + Lapatinib
LapatinibDRUG

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

Also known as: Tykerb, GW572016
Arm A: Pazopanib + Lapatinib
Trastuzumab (Herceptin®)DRUG

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

Also known as: Herceptin
Arm B: Pazopanib + Trastuzumab

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with advanced cancer should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months.
  • Patients must have measurable or evaluable disease.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status \</= 2.
  • Abnormal organ function is permitted; however, patients must have : Plt \>/=100,000/, absolute neutrophil count (ANC) \>/=1500, total Bilirubin \</=2.0 mg/dl, Creatinine \</=2.0 mg/dl and Prothrombin Time/International Normalized Ratio/Partial Thromboplastin Time (PT/INR/PTT) within 1.5 X upper limit of normal (ULN).
  • A woman is eligible to enter and participate in the study if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had a hysterectomy, bilateral oophorectomy (ovariectomy), bilateral tubal ligation, is post-menopausal (total cessation of menses for ≥ 1 year); OR if of childbearing potential, has a negative serum pregnancy test at screening, and agrees to use adequate contraception.
  • A man with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study.
  • Signed informed consent approved by the Institutional Review Board prior to patient entry.
  • Expanded Cohort only: Patients must have HER2 amplification, HER2 mutation, c-Met amplification, c-Met mutation, EML4-ALK translocation, or epidermal growth factor receptor (EGFR) mutation.

You may not qualify if:

  • Poorly-controlled hypertension (systolic blood pressure \[SBP\] \>/= 140 mmHg, or diastolic blood pressure \[DBP\]\>/= 90 mmHg).
  • Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes,congestive cardiac failure )
  • History of myocardial infarction, admission for unstable angina, cardiac angioplasty or stenting within three months of Day 1 of treatment period.
  • History of venous or arterial thrombosis within 3 months of Day 1 of treatment Period.
  • Excessive risk of bleeding or thrombosis as defined by stroke or severe bleeding within the prior 6 months.
  • Patients who received investigational drugs, chemotherapy or immunotherapy patient must be \>/= five half-lives or \>/= 3 weeks from the last dose of treatment, whichever is shorter.
  • Any major surgery or radiotherapy within 14 days of treatment.
  • Patients with a documented Left Ventricular Ejection Fraction \< 45%.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

MeSH Terms

Interventions

pazopanibLapatinibTrastuzumab

Intervention Hierarchy (Ancestors)

QuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • David S. Hong, MD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 12, 2011

First Posted

October 19, 2011

Study Start

October 1, 2011

Primary Completion

March 1, 2015

Study Completion

March 1, 2015

Last Updated

April 13, 2016

Record last verified: 2015-03

Locations

US(1)