Breast Cancer, Breast Neoplasms
Conditions
Keywords
Cancer of Breast, Cancer of the Breast
Brief summary
The purpose of the study is to determine if the two drugs can help patients feel better while causing the tumor to become smaller or disappear; evaluate the safety of giving both pemetrexed and gemcitabine in patients with advanced breast cancer.
Interventions
DRUGPemetrexed
500 mg/m2, intravenous (IV), every 14 days, until disease progression
DRUGGemcitabine
1500 mg/m2, intravenous (IV), every 14 days, until disease progression
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have received prior chemotherapy with Taxol (paclitaxel) or Taxotere (docetaxel). * Less than 3 different chemotherapy treatments for metastatic disease. * Prior treatment with hormonal and/or radiation therapy. * Must have disease that can be measured. * Must be able to take care of self needs for example personal hygiene
Exclusion criteria
* Must not be pregnant or breast-feeding. * Cancer that has spread to the brain. * Treatment with Gemcitabine or Pemetrexed * Unable to take folic acid or Vitamin B12 * Treatment for another cancer within the last 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Tumor Response | Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated | Best overall (confirmed) response recorded from start of treatment until disease progression/recurrence, start of other anti-tumor therapy/intervention, or end of trial, whichever comes first. Response must be confirmed at least 6 weeks from previous scans. Best overall response assignment depends on both measurement and confirmation criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of (Confirmed) Complete Response or Partial Response | Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated | Duration of response is calculated as (Date of First Disease Progression or Death as a Result of any Cause whichever Comes First - Date of First Objective Status Assessment of Confirmed CR or PR + 1)/(365.25/12). |
| Time to Progressive Disease | Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated | Time to progressive disease is calculated as (Date of First Disease Progression or Death Due to Disease under Study whichever Comes First - First Dose Date + 1)/(365.25/12). |
| Time to Treatment Failure | Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated | Time to treatment failure is calculated as (Date of First Disease Progression, Death as a Result of any Cause, or Early Discontinuation of Treatment Due to Adverse Event or Physician Perception of Lack of Efficacy or Patient and Physician Perception of Lack of Efficacy, whichever Comes First - First Dose Date + 1)/ (365.25/12) |
| Overall Survival | Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated | Overall survival time is calculated as (Date of Death as a Result of any Cause - First Dose Date + 1)/ (365.25/12). |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
At completion of the first stage of the trial, toxicities associated with the Day 8 dosing of gemcitabine were observed, and the protocol was amended to a bi-weekly schedule. Patients were analyzed separately according to the study drug schedule received.
Participants by arm
| Arm | Count |
|---|---|
| Bi-Weekly Schedule Pemetrexed: 500 mg/m2, intravenous (IV), every 14 days, until disease progression.
Gemcitabine: 1500 mg/m2, intravenous (IV), every 14 days, until disease progression. | 52 |
| 21-Day Schedule Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days, until disease progression.
Gemcitabine: 1000 mg/m2, intravenous (IV) on Days 1 and 8 of a 21-day cycle, until disease progression. | 21 |
| Total | 73 |
Baseline characteristics
| Characteristic | Bi-Weekly Schedule | 21-Day Schedule | Total |
|---|---|---|---|
| Age Continuous | 53.5 years | 50.7 years | 51.9 years |
| Current Pathological Diagnosis Adenocystic breast carcinoma | 0 paticipants | 1 paticipants | 1 paticipants |
| Current Pathological Diagnosis Breast carcinoma | 4 paticipants | 4 paticipants | 8 paticipants |
| Current Pathological Diagnosis Ductal breast carcinoma | 36 paticipants | 12 paticipants | 48 paticipants |
| Current Pathological Diagnosis Lobular breast carcinoma | 2 paticipants | 0 paticipants | 2 paticipants |
| Current Pathological Diagnosis No current pathological diagnosis | 2 paticipants | 0 paticipants | 2 paticipants |
| Current Pathological Diagnosis Other | 7 paticipants | 3 paticipants | 10 paticipants |
| Current Pathological Diagnosis Unknown | 1 paticipants | 1 paticipants | 2 paticipants |
| Karnofsky Performance Status (KPS) 100 - Normal no complaints; no evidence of disease | 17 participants | 6 participants | 23 participants |
| Karnofsky Performance Status (KPS) <=60 - Needs increasing assistance up to Death (0) | 0 participants | 0 participants | 0 participants |
| Karnofsky Performance Status (KPS) 70 - Unable to carry on normal activity | 4 participants | 1 participants | 5 participants |
| Karnofsky Performance Status (KPS) 80 - Activity with effort; some signs of disease | 11 participants | 5 participants | 16 participants |
| Karnofsky Performance Status (KPS) 90 - Normal activity; minor signs of disease | 19 participants | 9 participants | 28 participants |
| Karnofsky Performance Status (KPS) unknown | 1 participants | 0 participants | 1 participants |
| Menopausal Status at Cycle 0 Menopausal | 4 participants | 3 participants | 7 participants |
| Menopausal Status at Cycle 0 Post-Menopausal | 41 participants | 15 participants | 56 participants |
| Menopausal Status at Cycle 0 Pre-Menopausal | 7 participants | 3 participants | 10 participants |
| Patients with Current Pathological Diagnosis No | 2 participants | 0 participants | 2 participants |
| Patients with Current Pathological Diagnosis Yes | 50 participants | 21 participants | 71 participants |
| Race/Ethnicity African | 4 participants | 1 participants | 5 participants |
| Race/Ethnicity Caucasian | 44 participants | 20 participants | 64 participants |
| Race/Ethnicity East/Southeast Asian | 3 participants | 0 participants | 3 participants |
| Race/Ethnicity Hispanic | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 52 participants | 21 participants | 73 participants |
| Sex: Female, Male Female | 52 Participants | 21 Participants | 73 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Time (in months) from Current Pathological Diagnosis to Enrollment | 13.08 Months | 14.31 Months | 14.29 Months |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 51 / — | 21 / — |
| serious Total, serious adverse events | 17 / — | 7 / — |
Outcome results
Primary
Overall Tumor Response
Best overall (confirmed) response recorded from start of treatment until disease progression/recurrence, start of other anti-tumor therapy/intervention, or end of trial, whichever comes first. Response must be confirmed at least 6 weeks from previous scans. Best overall response assignment depends on both measurement and confirmation criteria.
Time frame: Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated
Population: Patients who received at least one dose of study drug (pemetrexed or gemcitabine) were included in the analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bi-Weekly Schedule | Overall Tumor Response | Partial Response | 8 participants |
| Bi-Weekly Schedule | Overall Tumor Response | Progressive Disease | 14 participants |
| Bi-Weekly Schedule | Overall Tumor Response | Stable Disease | 26 participants |
| Bi-Weekly Schedule | Overall Tumor Response | Unknown | 2 participants |
| Bi-Weekly Schedule | Overall Tumor Response | Complete Response | 2 participants |
| 21-Day Schedule | Overall Tumor Response | Unknown | 0 participants |
| 21-Day Schedule | Overall Tumor Response | Complete Response | 0 participants |
| 21-Day Schedule | Overall Tumor Response | Partial Response | 5 participants |
| 21-Day Schedule | Overall Tumor Response | Stable Disease | 10 participants |
| 21-Day Schedule | Overall Tumor Response | Progressive Disease | 6 participants |
Secondary
Duration of (Confirmed) Complete Response or Partial Response
Duration of response is calculated as (Date of First Disease Progression or Death as a Result of any Cause whichever Comes First - Date of First Objective Status Assessment of Confirmed CR or PR + 1)/(365.25/12).
Time frame: Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated
Population: Number of patients with a confirmed complete or partial response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bi-Weekly Schedule | Duration of (Confirmed) Complete Response or Partial Response | 5.85 months |
| 21-Day Schedule | Duration of (Confirmed) Complete Response or Partial Response | 4.17 months |
Secondary
Overall Survival
Overall survival time is calculated as (Date of Death as a Result of any Cause - First Dose Date + 1)/ (365.25/12).
Time frame: Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bi-Weekly Schedule | Overall Survival | 13.44 months |
| 21-Day Schedule | Overall Survival | 16.20 months |
Secondary
Time to Progressive Disease
Time to progressive disease is calculated as (Date of First Disease Progression or Death Due to Disease under Study whichever Comes First - First Dose Date + 1)/(365.25/12).
Time frame: Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated
Population: Intention to Treat analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bi-Weekly Schedule | Time to Progressive Disease | 3.19 months |
| 21-Day Schedule | Time to Progressive Disease | 4.01 months |
Secondary
Time to Treatment Failure
Time to treatment failure is calculated as (Date of First Disease Progression, Death as a Result of any Cause, or Early Discontinuation of Treatment Due to Adverse Event or Physician Perception of Lack of Efficacy or Patient and Physician Perception of Lack of Efficacy, whichever Comes First - First Dose Date + 1)/ (365.25/12)
Time frame: Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated
Population: Intention to Treat analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bi-Weekly Schedule | Time to Treatment Failure | 2.79 months |
| 21-Day Schedule | Time to Treatment Failure | 2.56 months |