Study of BKM120 or BYL719 and Capecitabine in Patients With Metastatic Breast Cancer

NCT01300962 | Completed Phase 1 DMC

• 2 other identifiers: LCCC 102411-0060
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I study has been designed to establish the safety, tolerability and maximum tolerated dose (MTD) of four separate regimens for patients with metastatic breast cancer: dose- escalating BKM120 when combined with capecitabine (Arm A), with capecitabine and trastuzumab (Arm C), or with capecitabine and lapatinib (Arm D) and dose- escalating BEZ235 when combined with capecitabine (Arm B).

Conditions

Metastatic Breast Cancer

Keywords

Xeloda; Capecitabine; BKM120; Lineberger Comprehensive Cancer Center; Metastatic; BYL719 Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose

  Maximum Tolerated Dose (MTD) will be the highest does at which less than or equal to 1 out of 6 patients have experienced a dose limiting toxicity (DLT)

  two years

• Dose limiting toxicity (DLT)

  Dose-limiting toxicities (DLT) will be defined per NCI Common Terminology Criteria for Adverse Events version 4 (CTCAE v4)

  two years

Secondary Outcomes (2)

• Objective Response

  two years

• Best Overall Response

  two years

Study Arms (4)

BYL719 ARM B

EXPERIMENTAL

Treatment with BYL719 and Capecitabine

Drug: Capecitabine; Drug: BYL719

BKM120 ARM A

EXPERIMENTAL

Treatment with BKM120 and capecitabine

Drug: BMK120; Drug: Capecitabine

ARM C

EXPERIMENTAL

BKM 120 plus capecitabine plus trastuzumab

Drug: BMK120; Drug: Capecitabine; Drug: Trastuzumab

ARM D

EXPERIMENTAL

BKM120 plus capecitabine plus lapatinib

Drug: BMK120; Drug: Capecitabine; Drug: Lapatinib

Interventions

BMK120 DRUG

BKM120 PO 50, 80 or 100mg every day for each day of each 21 day cycle. Number of cycles: until progression of disease; unacceptable toxicity, withdrawal or death.

ARM C; ARM D; BKM120 ARM A

Capecitabine DRUG

875-1250mg/m2 PO BID for two weeks followed by one week rest every three week cycle. Number of cycles: until progression of disease, unacceptable toxicity, withdrawal or death.

Also known as: Xeloda

ARM C; ARM D; BKM120 ARM A; BYL719 ARM B

BYL719 DRUG

BYL719 200mg PO BID for 21 days (3 weeks) in combination with capecitabine 1000 mg/m2 PO BID for 2 weeks

BYL719 ARM B

Trastuzumab DRUG

trastuzumab infusion on day 1 of each cycle.

Also known as: Herceptin

ARM C

Lapatinib DRUG

lapatinib daily for 21 days in each cycle.

Also known as: Tykerb

ARM D

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years (no upper age limit)
• confirmed pathologic diagnosis of breast cancer which is metastatic and for which capecitabine is a reasonable treatment option
• ARMS C \& D: Histologically confirmed HER2+ breast cancer: IHC 3+ or fluorescence in situ hybridization \[FISH\] amplified; by clinical assay on either primary or metastatic tumor
• Brain metastases permitted in Arms A and B if:
• CNS-directed treatment has been given;
• No CNS-directed therapy for the past 3 months, including glucocorticoids; AND
• CNS disease has been clinically and radiographically stable for at least 8 weeks
• Brain metastases permitted in Arms C and D if:
• CNS-directed treatment has been given;
• weeks interval between whole brain radiation therapy and initiation of protocol-based therapy;
• weeks interval between stereotactic radiosurgery or gamma knife (or equivalent) and initiation of protocol-based therapy;
• CNS disease has been clinically and radiographically stable for at least 4 weeks
• In Arm C, if patient on glucocorticoids, must be on stable (4 weeks) dose of no more than 2 mg/day of dexamethasone or equivalent.
• In Arms B and D, no steroids are allowed.
• Measurable or non-measurable (but evaluable) disease as defined via RECIST 1.1

You may not qualify if:

• Receiving concurrent endocrine, cytotoxic, or biologic agent(s) or within time limits specified above prior to study day 1
• Receiving any other investigational agents currently, or within time limits specified above prior to study day 1
• Received wide field radiotherapy ≤4 weeks, or SRS or gamma knife for brain metastasis ≤ 2 weeks or limited field radiation for palliation ≤2 weeks prior to starting either BYL719 or BKM120 or have not recovered from side effects of such therapy
• Have undergone major surgery ≤2 weeks prior to starting BKM120 or BYL719 or have not recovered from side effects of such therapy
• Prior treatment with treatment doses of capecitabine (prior radio-sensitizing doses of capecitabine are allowed as long as the patient did not progress on capecitabine)
• Prior treatment with a PI3K inhibitor
• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• Treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued
• Currently receiving treatment with medication known to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
• Patients currently receiving chronic systemic treatment with steroids or another immunosuppressive agent; NOTE: This restriction regarding choice of glucocorticoid does not apply should patient need \<2 week course of glucocorticoid for treatment of non-infectious pneumonitis during study, or if ARM C patient with brain metastases treated with glucocorticoid is enrolled. Topical applications (e.g., rash), inhaled sprays, eye drops or local injections of steroids are allowed.
• Known coagulopathies, and those who require therapeutic anticoagulation with coumarin-derivative anticoagulants
• Presence of acute or chronic liver, renal disease, or pancreatitis
• For all Arms, patients with poorly controlled diabetes mellitus, and/or with clinical signs, and/or steroid-induced diabetes mellitus; for Arm B, patients requiring insulin treatment
• History of gestational diabetes mellitus
• Known diagnosis of human immunodeficiency virus (HIV) infection

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (2)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Related Links

• UNC Lineberger Comprehensive Cancer Center

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Capecitabine; Alpelisib; Trastuzumab; 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)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Claire Dees

  University of North Carolina Lineberger Comprehensive 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: February 17, 2011
• First Posted: February 23, 2011
• Study Start: August 1, 2011
• Primary Completion: February 7, 2017
• Study Completion: December 31, 2018
• Last Updated: December 4, 2023

Record last verified: 2023-11

Locations

US (2)