Advanced or Metastatic Solid Tumors, Advanced or Metastatic Breast Cancer
Conditions
Brief summary
The purpose of this clinical trial is to test whether treatment of patients with advanced or metastatic solid tumors or breast cancer with Abraxane plus Vidaza is safe and results in good tumor response. All patients enrolling in this study will receive treatment with Abraxane and Vidaza. Safety will be assessed by adverse events, laboratory results and performance status. Tumor response will be measured by RECIST criteria.
Detailed description
The phase I part of the study will enroll patients with advanced or metastatic solid tumors who have failed at least one previous treatment. The purpose of the phase I part is to assess the safety of the investigational treatment and select the recommended phase II dose-regimen. The phase II part of the study will enroll patients with advanced or metastatic HER2-negative breast cancer who have not received treatment for their metastatic disease. The purpose of the phase II part of the study is to assess safety and efficacy of the investigational treatment in breast cancer. The study doctor will determine what phase patients will be enrolled in.
Interventions
50mg/m2, 75mg/m2 or 100mg/m2 daily for 5 days for each 4-week cycle
100mg/m2 weekly for 3 weeks of each 4-week cycle
Sponsors
Celgene Corporation
University of Utah
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
1. For phase I, any solid tumors, including lymphoma, that progressed or were stable as best response on at least one previous therapy and are evaluable. 2. For phase II, pathologically confirmed breast cancer, measurable disease, no prior treatments for recurrent or metastatic breast cancer. 3. Her-2/neu negative (Phase II) 4. Negative pregnancy test for female subjects 5. Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacitidine or nab-paclitaxel. investigator. 6. Male or female for phase I and female for phase II, \>19 years of age and any race.
Exclusion criteria
1. Major surgery, radiotherapy, chemotherapy or investigational agents within 4 weeks of treatment day 1 2. Known brain metastases 3. Prior taxanes (except for adjuvant therapy more than 6 months prior to treatment day 1) (phase II) 4. Active infection requiring antibiotic therapy 5. History of allergy or hypersensitivity to nab-paclitaxel, albumin or a taxane 6. Grade 2 or greater motor or sensory neuropathy 7. Prior cytotoxic chemotherapy for recurrent or metastatic breast cancer (phase II portion) 8. Uncontrolled hypertension, arrhythmia, congestive heart failure or angina. Patients who have had a myocardial infarction or cardiac surgery should be at least 6 months from the event and free of active symptoms. 9. Known or suspected hypersensitivity to azacitidine or mannitol 10. Pregnant or breast feeding 11. Patients with advanced malignant hepatic tumors 12. Malignancy other than breast carcinoma (phase II) 13. Known HIV infection or chronic hepatitis B or C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Percentage of Participants Responding to Treatment | 6 months | Azacitidine is set at 75mg/m2 and Nab-paclitaxel is set at100mg/m2 based on the number of participants responding to treatment as measured per RECIST v1 criteria. |
| Phase II: Percentage of Participants With Objective Response Rate (ORR) Measured Using RECIST 1.0 Criteria | 1.5 years | Objective response rate (ORR) will be measured using RECIST 1.0 criteria. The best response, including complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), for each patient will be summarized. For target lesions, Complete Response is defined as disappearance of all target lesions for at least 4 weeks; Partial Response consists of at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD, for at least 4 weeks; Progressive Disease consists of at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease consists of neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ER+ Status | 2 years | Tissue SPARC protein will be assessed using archival tumor blocks. In addition, in patients who have easily accessible tumors, such as lymph nodes, cutaneous or subcutaneous lesions, and who have consented to sample collection, biopsies will be taken twice: before cycle 1 day 1 treatment, and cycle 3 day 8 (+/- 3 days). |
| Progression-free Survival | 2 years | Progression-free survival (PSF) is defined as the length of time during and after treatment in which a patient is living with a disease that does not get worse. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase II Azacitidine is set at 75mg/m2 and Nab-paclitaxel is set at100mg/m2 | 14 |
| Phase I Azacitidine (Vidaza): 50mg/m2, 75mg/m2 or 100mg/m2 daily for 5 days for each 4-week cycle
Nab-paclitaxel (Abraxane): 100mg/m2 weekly for 3 weeks of each 4-week cycle | 16 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | disease progression | 2 | 0 |
| Overall Study | noncompliance | 1 | 0 |
Baseline characteristics
| Characteristic | Phase II | Total | Phase I |
|---|---|---|---|
| Age, Continuous | 65 years | 63.5 years | 62 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 22 Participants | 10 Participants |
| Region of Enrollment United States | 14 Participants | 30 Participants | 16 Participants |
| Sex: Female, Male Female | 14 Participants | 27 Participants | 13 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Phase II: Percentage of Participants With Objective Response Rate (ORR) Measured Using RECIST 1.0 Criteria
Objective response rate (ORR) will be measured using RECIST 1.0 criteria. The best response, including complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), for each patient will be summarized. For target lesions, Complete Response is defined as disappearance of all target lesions for at least 4 weeks; Partial Response consists of at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD, for at least 4 weeks; Progressive Disease consists of at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease consists of neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: 1.5 years
Population: Of the 14 patients enrolled on the Phase II portion of trial, one patient opted out off trial after 1 cycle because of toxicity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 | Phase II: Percentage of Participants With Objective Response Rate (ORR) Measured Using RECIST 1.0 Criteria | 53.8 percentage of participants |
Primary
Phase I: Percentage of Participants Responding to Treatment
Azacitidine is set at 75mg/m2 and Nab-paclitaxel is set at100mg/m2 based on the number of participants responding to treatment as measured per RECIST v1 criteria.
Time frame: 6 months
Population: 16 patients were evaluable for toxicity. 13 were evaluable for response per RECIST v1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 | Phase I: Percentage of Participants Responding to Treatment | 61.5 percent of participants with response |
Secondary
Number of Participants With ER+ Status
Tissue SPARC protein will be assessed using archival tumor blocks. In addition, in patients who have easily accessible tumors, such as lymph nodes, cutaneous or subcutaneous lesions, and who have consented to sample collection, biopsies will be taken twice: before cycle 1 day 1 treatment, and cycle 3 day 8 (+/- 3 days).
Time frame: 2 years
Population: Of the 14 patients enrolled on the Phase II portion of trial, one patient opted out off trial after 1 cycle because of toxicity. Thirteen patients were evaluated for ER+ status.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 | Number of Participants With ER+ Status | 11 participants were ER+ |
Secondary
Progression-free Survival
Progression-free survival (PSF) is defined as the length of time during and after treatment in which a patient is living with a disease that does not get worse.
Time frame: 2 years
Population: Data were not collected.