Lapatinib With Sirolimus or Metformin

NCT01087983 | Completed Phase 1

• 2 other identifiers: 2009-0743NCI-2011-00563
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of 2 different combinations of drugs that can be given to patients with advanced cancer. The first combination of drugs is Tykerb (lapatinib) and Rapamune (sirolimus), and the second combination is lapatinib and Glucophage (metformin). The safety of these drug combinations will also be studied.

Conditions

Advanced Cancers

Keywords

Metastatic cancer; Lapatinib; Tykerb; Metformin; Glucophage; Sirolimus; Rapamune

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Lapatinib in Combination with Sirolimus or Metformin

  MTD is defined as the highest dose studied in which the incidence of dose-limiting toxicity (DLT) is less than 33%.

  21 day cycle

Study Arms (2)

Lapatinib + Sirolimus

EXPERIMENTAL

Lapatinib starting oral dose of 500 mg daily for 21 day cycle. Sirolimus starting oral dose 1 mg daily.

Drug: Lapatinib; Drug: Sirolimus

Lapatinib + Metformin

EXPERIMENTAL

Lapatinib starting oral dose of 500 mg daily for 21 day cycle. Metformin Starting oral dose 1000 mg daily.

Drug: Lapatinib; Drug: Metformin

Interventions

Lapatinib DRUG

Starting oral dose of 500 mg daily for 21 day cycle.

Also known as: Tykerb, GW572016

Lapatinib + Metformin; Lapatinib + Sirolimus

Sirolimus DRUG

Starting oral dose 1 mg daily.

Also known as: Rapamune

Lapatinib + Sirolimus

Metformin DRUG

Starting oral dose 1000 mg daily.

Also known as: Glucophage

Lapatinib + Metformin

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
• Patients must be at least 3 weeks beyond their previous cytotoxic treatment. Patient must wait at least 5 half-lives or 3 weeks, whichever is shorter, from their previous targeted or biologic therapy; In addition, patients must be at least 3 weeks beyond the last session of radiation therapy or major surgery. Local palliative radiation therapy that is not delivered to all target lesions is allowed immediately before or during treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status should be less or equal to 3
• Patients must have normal organ and marrow function defined as: absolute neutrophil count (ANC) \>/= 750/mL; platelets \>/= 50,000/mL; creatinine \</= 2x upper limit of normal (ULN) for the Sirolimus Arm and creatinine \< 1.5 mg/dl for the Metformin arm; total bilirubin \</=2.0 (For patients with Gilbert syndrome, bilirubin level \> 2 could will be allowed on study if the hyperbilirubinemia is believed to be secondary only to the Gilbert syndrome); ALT (SGPT) \</= 5x ULN; Exception for patients with liver metastasis: total bilirubin \</= 3x ULN; ALT (SGPT) \</= 8x ULN.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose
• Patients must be able to understand and be willing to sign a written informed consent document
• Patients with treated brain metastases are allowed in both arms of the study.

You may not qualify if:

• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
• Pregnant or lactating women.
• History of hypersensitivity to Lapatinib or any component of the formulation.
• Patients who have malabsorption syndrome
• Patients with class III or IV congestive heart failure as defined by New York Heart Association functional classification system
• Patients unwilling or unable to sign informed consent document
• History of hypersensitivity to Sirolimus or any component of the formulation (for Lapatinib and Sirolimus arm only)
• History of hypersensitivity to metformin or any component of the formulation (for Lapatinib and Metformin arm only)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Lapatinib; Sirolimus; Metformin

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Organic Chemicals; Biguanides; Guanidines; Amidines

Study Officials

• Filip Janku, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

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: March 15, 2010
• First Posted: March 16, 2010
• Study Start: March 1, 2010
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: November 11, 2015

Record last verified: 2015-11

Locations

US (1)