Metastatic Breast Cancer
Conditions
Brief summary
A published phase 2 study reported that lonafarnib was administered as a single agent via continuous or intermittent oral dosing to 76 women with advanced breast cancer who were previously treated with chemotherapy and/or with endocrine therapy. Objective response rates of approximately 10% were observed. This study will determine the rate of progression-free survival of patients with metastatic breast cancer who receive lonafarnib.
Detailed description
OUTLINE: This is a multi-center study Patients will be treated with lonafarnib 200 mg PO BID daily on days 1-21 of every 21-day cycle until progression of disease, unacceptable toxicity, or investigator's discretion. 1 Cycle = 21 days of lonafarnib (plus the time required to recover from toxicity if encountered). ECOG Performance Status 0-1 Life Expectancy: Not Specified Hematopoietic: * Platelets \> 100 K/mm3 * Absolute Neutrophil Count (ANC) \> 1.2 K/mm3 * Hemoglobin ≥ 9 g/dl * Serum potassium ≥ 3.3 mmol/L Hepatic: * Aspartate transaminase (AST) ≤ 5.0 x ULN * Alanine transaminase (ALT) ≤ 5.0 x ULN * Total bilirubin \< 1.5 x ULN Renal: * Calculated creatinine clearance (using Cockcroft-Gault formula) \> 45 cc/min Cardiovascular: * No history of Torsades de Pointes, ventricular tachycardia, ventricular fibrillation or ventricular flutter
Interventions
DRUGLonafarnib
All registered patients will be treated with Lonafarnib 200 mg PO BID daily on days 1-21 of every 21-day cycle until progression of disease, unacceptable toxicity, or investigator's discretion.
Sponsors
Schering-Plough
Hoosier Cancer Research Network
George Sledge
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytological confirmed adenocarcinoma of the breast with locally advanced or metastatic disease. * Must be able and willing to enroll in the companion study entitled Predicting Response and Toxicity in Patients Receiving Lonafarnib for Breast Cancer: A Multicenter Genomic, Proteomic and Pharmacogenomic Correlative Study: Hoosier Oncology Group COE-03. * Must have measurable disease per RECIST as evaluated by imaging within 28 days prior to registration for protocol therapy. * Must be willing to not drink grapefruit juice for the duration of lonafarnib therapy. * Previously radiated area(s) must not be the only site of disease for study entry. * Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time of consent until at least 90 days following completion of study treatment. * Females of childbearing potential must have a negative pregnancy test within 7 days prior to registration for protocol therapy. Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. * Females must not be breastfeeding. * Written informed consent and HIPAA authorization for release of personal health information. * Age \> 18 years
Exclusion criteria
* No history or radiologic evidence of CNS metastases including previously treated, resected or asymptomatic brain lesions or leptomeningeal involvement (head CT or MRI must be obtained within 42 days prior to registration for protocol therapy). * No treatment with any investigational agent within 30 days prior to registration for protocol therapy. * No history of Torsades de Pointes, ventricular tachycardia, ventricular fibrillation or ventricular flutter. * No history of syncope. * No history of seizures. * No prolonged QTc interval \> 450msec on pre-entry electrocardiogram obtained within 28 days prior to registration for protocol therapy. * No history of hypokalemia that cannot be corrected prior to registration for protocol therapy. * No radiation within 14 days prior to registration for protocol therapy. Patients must have recovered from the acute toxic effects prior to registration for protocol therapy. * No prior chemotherapy within 21 days prior to registration for protocol therapy. * No clinically active serious infections as judged by the treating investigator (CTC v3, \> Grade 2) including known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C. * Following concomitant medications must be discontinued 7 days prior to registration for protocol therapy and for the duration of lonafarnib therapy: bisphosphonates, including but not limited to etidronate (Didronel), pamidronate (Aredia), alendronate (Fosamax), risedronate (Actonel), zoledronate (Zometa or Reclast), ibandronate (Boniva), ethinylestradiol, gestodene, itraconazole, ketoconazole, cimetidine, erythromycin, carbamazepine, high dose chronic steroids, phenobarbital, phenytoin, rifampin (rifampicin), sulfinpyrazone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 18 months | To determine progression-free survival of lonafarnib in patients with metastatic breast cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 18 months | To determine overall response rate. |
| Toxicity Profile of Lonafarib | 18 months | To determine the toxicity profile of lonafarnib in this patient population. |
| Clinical Benefit Response Rate (Complete Response (CR)+Partial Response(PR)+Stable Disease(SD) > 180 Day Duration). | 18 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lonafarnib All registered patients will be treated with Lonafarnib 200 mg PO BID daily on days 1-21 of every 21-day cycle until progression of disease, unacceptable toxicity, or investigator's discretion.
Lonafarnib: All registered patients will be treated with Lonafarnib 200 mg PO BID daily on days 1-21 of every 21-day cycle until progression of disease, unacceptable toxicity, or investigator's discretion. | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Lonafarnib |
|---|---|
| Age, Continuous | 56 years |
| Estrogen Receptor (ER)/Progesterone Receptor (PR)/ HER2 Status ER- | 9 participants |
| Estrogen Receptor (ER)/Progesterone Receptor (PR)/ HER2 Status ER+ | 15 participants |
| Estrogen Receptor (ER)/Progesterone Receptor (PR)/ HER2 Status HER2- | 17 participants |
| Estrogen Receptor (ER)/Progesterone Receptor (PR)/ HER2 Status HER2+ | 3 participants |
| Estrogen Receptor (ER)/Progesterone Receptor (PR)/ HER2 Status PR- | 13 participants |
| Estrogen Receptor (ER)/Progesterone Receptor (PR)/ HER2 Status PR+ | 11 participants |
| Estrogen Receptor (ER)/Progesterone Receptor (PR)/ HER2 Status Unknown | 4 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Number of Prior Therapies | 8.4 Prior Therapies |
| Primary Tumor Diagnosis Breast Carcinoma | 14 participants |
| Primary Tumor Diagnosis Ductal Breast Carcinoma | 20 participants |
| Primary Tumor Diagnosis Lobular Breast Carcinoma | 1 participants |
| Primary Tumor Diagnosis Other | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 7 / 29 |
Outcome results
Primary
Progression Free Survival
To determine progression-free survival of lonafarnib in patients with metastatic breast cancer.
Time frame: 18 months
Population: 20 participants were eligible for analysis via the Kaplan-Meier method. PFS assessed via RECIST criteria.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lonafarnib | Progression Free Survival | 65.5 days |
Secondary
Clinical Benefit Response Rate (Complete Response (CR)+Partial Response(PR)+Stable Disease(SD) > 180 Day Duration).
Time frame: 18 months
Population: 20 evaluable subjects were analyzed for Clinical Benefit Rate (CR+PR+SD\>180 days per RECIST criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lonafarnib | Clinical Benefit Response Rate (Complete Response (CR)+Partial Response(PR)+Stable Disease(SD) > 180 Day Duration). | 0 participants |
Secondary
Overall Response Rate
To determine overall response rate.
Time frame: 18 months
Population: 17 participants were evaluable for Overall Response Rate analysis using RECIST criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lonafarnib | Overall Response Rate | CR | 0 participants |
| Lonafarnib | Overall Response Rate | PR | 0 participants |
| Lonafarnib | Overall Response Rate | SD | 5 participants |
| Lonafarnib | Overall Response Rate | PD | 12 participants |
Secondary
Toxicity Profile of Lonafarib
To determine the toxicity profile of lonafarnib in this patient population.
Time frame: 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lonafarnib | Toxicity Profile of Lonafarib | Grade 3/4 Diarrhea | 6 participants |
| Lonafarnib | Toxicity Profile of Lonafarib | Grade 3/4 Dehydration | 2 participants |
| Lonafarnib | Toxicity Profile of Lonafarib | Grade 5 Encephalopathy | 1 participants |
| Lonafarnib | Toxicity Profile of Lonafarib | Disease Progression NOS | 1 participants |