GCC 0845:Vorinostat and Lapatinib in Advanced Solid Tumors and Advanced Breast Cancer to Evaluate Response and Biomarkers

NCT01118975 | Terminated Phase 1 Results DMC

• 1 other identifier: HP-00040048
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to find out how safe and how well the combination of lapatinib and vorinostat works against advanced cancers.

Conditions

Breast Cancer; Neoplasm Metastasis

Keywords

lapatinib ditosylate; Zolinza (vorinostat); Cancer Stem Cells

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities

  Safety and tolerability were assessed. Adverse events and dose limiting toxicities were recorded during an escalting dose pilot phase.

  6 weeks

• Clinical Benefit Rate

  The Clinical Benefit Rate is the number of patients with either Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for ≥ 6 months

  Radiological evaluations are performed every 12 weeks to determine disease status

Study Arms (2)

Pilot Phase - Vornistat 200 to 400mg + Lapatinib

EXPERIMENTAL

lapatinib 1,250 mg continuous daily and escalating doses of vorinistat (200mg run-up, 300mg, and 400mg 4 days on 3 days off)

Drug: Vorinostat; Drug: Lapatinib

Phase II - Vorinistat 400mg + Lapatinib

EXPERIMENTAL

lapatinib 1,250 mg continuous daily and vorinostat 400 mg 4 days on 3 days

Drug: Vorinostat; Drug: Lapatinib

Interventions

Vorinostat DRUG

300 mg 4 days on then 3 days off As defined in the protocol, the dose of vorinostat was increased to 400 mg 4 days on then 3 days off in the pilot phase because the adverse event threshold was not met. In the Phase II cohort, the dose of vorinistat was 400 mg 4 days on and 3 days off.

Also known as: Zolinza

Phase II - Vorinistat 400mg + Lapatinib; Pilot Phase - Vornistat 200 to 400mg + Lapatinib

Lapatinib DRUG

1,250 mg once daily

Also known as: Tykerb

Phase II - Vorinistat 400mg + Lapatinib; Pilot Phase - Vornistat 200 to 400mg + Lapatinib

Eligibility Criteria

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

You may qualify if:

• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
• Consent for peripheral blood sampling for analysis of circulating tumor cells.
• Patients must have adequate organ and marrow function as defined by the protocol.
• Female patients with histologically confirmed adenocarcinoma of the breast with recurrent local-regional disease, or metastatic disease that have progressed after treatment with regimens that include an anthracycline, a taxane, or trastuzumab.
• Human Epidermal growth factor Receptor 2 (HER2) positive in the primary or secondary tumor tissue as defined by:
• Grade 3plus staining intensity (on a scale of 0 to 3) by means of Immunohistochemistry (IHC) analysis OR
• Gene amplification on fluorescence in situ hybridization (FISH) greater than or equal to 2.2.
• Patients must have measurable disease by the Response Evaluation Criteria In Solid Tumors (RECIST)criteria at the time of enrollment.
• Prior trastuzumab therapy is allowed. Trastuzumab should be stopped at least 4 weeks prior to enrollment.

You may not qualify if:

• Patients receiving any other investigational agents.
• Prior exposure to lapatinib, vorinostat, or other Histone deacetylase (HDAC) inhibitors. Prior valproic acid exposure is allowed providing this is a greater than or equal to 30 days wash-out period.
• History of allergic reactions or hypersensitivity to compounds of similar chemical or biologic composition to vorinostat or lapatinib.
• Patients with history of clinically significant or uncontrolled cardiac disease, as defined by the protocol, or any significant cardiac condition that in the judgment of the investigator is unsuitable.
• Significant chronic or recent (less than 30 days) acute gastrointestinal disorder with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption, or Grade 2 or greater diarrhea of any etiology at baseline).
• Prior exposure to more than 360 mg/m2 doxorubicin or liposomal doxorubicin, more than 120 mg/m2 mitoxantrone, or more than 90 mg/m2 idarubicin, or elevated baseline cardiac troponin T (more than upper limit of normal).
• Patients with active Central Nervous System (CNS) metastasis and/or carcinomatous meningitis are excluded. Patients with CNS metastasis who have completed a course of therapy would be eligible for the study provided they are clinically stable for 3 weeks prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis and (2) off steroids and/or anticonvulsants, for at least 4 weeks before an enrollment.
• Female patient that is pregnant or breastfeeding or expecting to conceive during the study. Women able to have children must have a negative pregnancy test prior to enrollment. All patients must use two effective methods of contraception (including a barrier method) during treatment and for 12 weeks after stopping treatment.
• The patient is known to be Human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C-positive (test results are not required in order to participate).
• Patients with current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirement.
• Previous or current systemic malignancy within the past 3 years other than the following: Female- breast cancer or adequately treated carcinoma in-situ of the cervix, or Female and Male- basal/squamous carcinoma of the skin.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• University of Maryland Greenebaum Cancer Center: collaborator

Study Sites (1)

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Vorinostat; Lapatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The most important limitation of this study is that the Phase II efficacy portion was terminated early by the sponsor.

Results Point of Contact

• Title: Michelle Medeiros
• Organization: University of Maryland

mmedeiros@umm.edu

410-328-1160

Study Officials

• Saranya Chumsri, MD

  University of Maryland, College Park

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: May 5, 2010
• First Posted: May 7, 2010
• Study Start: March 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: November 13, 2019
• Results First Posted: April 24, 2014

Record last verified: 2019-10

Locations

US (1)