Pancreatic Neoplasms
Conditions
Keywords
pancreatic cancer, metastatic, chemotherapy naive
Brief summary
The purpose of this study is to determine if imexon in combination with gemcitabine could improve overall survival as compared to gemcitabine alone in subjects with pancreatic cancer that has spread to other organs such as the liver or lungs. The study will also look at the safety of the combination as compared to gemcitabine alone. Participants in the study will be randomly assigned to either treatment and neither the participant or their doctors will know which treatment they will be receiving.
Interventions
DRUGimexon in combination with gemcitabine
875 mg/m\^2 imexon IV + 1000 mg/m\^2 gemcitabine IV
DRUGimexon placebo + gemcitabine
imexon placebo IV + 1000 mg/m\^2 gemcitabine IV
Sponsors
AmpliMed Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with histologically or cytologically confirmed, chemotherapy naive, metastatic pancreatic adenocarcinoma (Stage IV). This does not include patients with only locally advanced pancreatic cancer. 2. At least one unidimensional measurable metastatic lesion by contrast enhanced CT scan (or MRI in patients ineligible for contrast enhanced CT) that are outside any prior radiation port. 3. Age at least 18 years. 4. ECOG performance status 0 or 1. 5. No prior chemotherapy or radiation therapy. 6. Projected life expectancy at least 2 months. 7. If female, neither pregnant nor lactating. 8. If of child bearing potential must agree to, and be able to use adequate contraception. 9. Concomitant disease: No respiratory insufficiency requiring oxygen therapy; no angina at rest; no myocardial infarction in previous 3 months; no life threatening ventricular arrhythmias. No uncompensated CHF or NY Heart Association class 3 or 4 cardiac disease. 10. No other concurrent active malignancy. 11. No infection requiring parenteral antibiotic therapy at the start of protocol treatment. 12. Laboratory values within the following criteria: Hgb greater than or equal to 9 gm/dL WBC greater than or equal 3,500/mm\^3 ANC greater than or equal 1,500/mm\^3 Platelet count greater than or equal 100,000/mm\^3 Creatinine greater than or equal 2.0 Bilirubin less than or equal to 2.0 Hepatic enzymes (AST, ALT) less than or equal 3 times upper limit of normal (ULN) 13. G6PD level greater than or equal lower limit of normal (LLN). 14. Able to render informed consent and follow protocol requirements.
Exclusion criteria
1. Patients with locally advanced, non-metastatic pancreas cancer (Stage III or below). 2. Age less than 18 years. 3. ECOG performance status 2 or greater. 4. Prior anticancer drug therapy for metastatic disease. 5. Ascites. 6. Prior abdominal or thoracic surgery \< 4 weeks before the start of therapy. 7. Current or prior brain metastases. Brain MRI or CT required pre-registration only if the patient has CNS symptoms indicating a need for evaluation. 8. Life expectancy projected less than 2 months. 9. Pregnancy or lactation. 10. Unable or unwilling to utilize medically acceptable contraception if of childbearing potential. 11. Laboratory parameters outside of specified ranges, (see above). 12. Infection requiring parenteral antibiotics. 13. NY Heart Association stage 3 or 4 heart disease. 14. Unable to render informed consent. 15. Failure to meet any of the eligibility criteria as outlined above.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival for the Intent to Treat Population | up to 2 years | To compare the overall survival duration of the two treatment arms. Overall survival is measured from the time of randomization until reported death. Subjects were censored at last time known alive if lost to follow-up. Alive patients were censored at the last survival follow-up. Follow-up was monthly after off study treatment. |
| To Evaluate and Compare the Tolerability and Toxicity of the Two Treatment Arms by Comparing Adverse Events | Adverse events were collected from the time of treatment until the participant went off study treatment, an average of 4 months | Number of Participants with Adverse Events were compared between the two arms to detect any differences in number or types of events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rates of the Two Treatment Arms | one year | Objective response is measured by tumor reduction as defined in the RECIST criteria. Tumor shrinkage must be at least 30% to qualify as an objective response. |
| Progression Free Survival | one year | To compare the median progression free survival (PFS) of the two treatment arms. Progression free survival is measured from randomization until the subject has documented disease progression by an objective measure. Subjects were censored if no documented progression had occurred at the one year time point. Subjects must be alive with no more than 20% increase in tumor size to qualify for progression free survival. Changes in tumor size are defined by RECIST criteria. |
Countries
United States
Participant flow
Recruitment details
Recruitment period was from April 2008 to May 2009. Enrollment occurred at 34 clinical centers in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Amplimexon (Imexon) + Gemcitabine Amplimexon 875 mg/m\^2 + gemcitabine 1000 mg/m\^2 | 72 |
| Imexon Placebo + Gemcitabine Placebo 875 mg/m\^2+ gemcitabine 1000 mg/m\^2 | 70 |
| Total | 142 |
Baseline characteristics
| Characteristic | Imexon Placebo + Gemcitabine | Amplimexon (Imexon) + Gemcitabine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 39 Participants | 38 Participants | 77 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 34 Participants | 65 Participants |
| Age, Continuous | 64.9 years STANDARD_DEVIATION 11.1 | 66.1 years STANDARD_DEVIATION 10.6 | 65.5 years STANDARD_DEVIATION 10.8 |
| Region of Enrollment United States | 70 participants | 72 participants | 142 participants |
| Sex: Female, Male Female | 31 Participants | 31 Participants | 62 Participants |
| Sex: Female, Male Male | 39 Participants | 41 Participants | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 67 | 68 / 68 |
| serious Total, serious adverse events | 51 / 67 | 44 / 68 |
Outcome results
Primary
Overall Survival for the Intent to Treat Population
To compare the overall survival duration of the two treatment arms. Overall survival is measured from the time of randomization until reported death. Subjects were censored at last time known alive if lost to follow-up. Alive patients were censored at the last survival follow-up. Follow-up was monthly after off study treatment.
Time frame: up to 2 years
Population: Intention to treat with subjects who were alive at the time of the survival analysis or lost to follow-up were considered censored at the last date the subject was known to be alive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amplimexon (Imexon) + Gemcitabine | Overall Survival for the Intent to Treat Population | 5.2 months |
| Imexon Placebo + Gemcitabine | Overall Survival for the Intent to Treat Population | 6.8 months |
Comparison: The hypothesis that survival curves were equal in the two treatment groups was tested with a one-sided logrank test at the alpha-0.2 level, one sided. The power of this test is 80% for detecting the hypothesized increase in median survival of 2.4 months for subjects in the experimental arm.p-value: 0.2Log Rank
Primary
To Evaluate and Compare the Tolerability and Toxicity of the Two Treatment Arms by Comparing Adverse Events
Number of Participants with Adverse Events were compared between the two arms to detect any differences in number or types of events
Time frame: Adverse events were collected from the time of treatment until the participant went off study treatment, an average of 4 months
Population: This includes only those subjects that received at least 1 dose of study treatment. There were 67 subjects in the imexon + gemcitabine arm and 68 in the placebo + gemcitabine arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amplimexon (Imexon) + Gemcitabine | To Evaluate and Compare the Tolerability and Toxicity of the Two Treatment Arms by Comparing Adverse Events | 67 participants |
| Imexon Placebo + Gemcitabine | To Evaluate and Compare the Tolerability and Toxicity of the Two Treatment Arms by Comparing Adverse Events | 68 participants |
Secondary
Objective Response Rates of the Two Treatment Arms
Objective response is measured by tumor reduction as defined in the RECIST criteria. Tumor shrinkage must be at least 30% to qualify as an objective response.
Time frame: one year
Population: Per protocol, response evaluable population was treated and had baseline and at least one response evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amplimexon (Imexon) + Gemcitabine | Objective Response Rates of the Two Treatment Arms | 13.2 percent of responses |
| Imexon Placebo + Gemcitabine | Objective Response Rates of the Two Treatment Arms | 16.4 percent of responses |
Secondary
Progression Free Survival
To compare the median progression free survival (PFS) of the two treatment arms. Progression free survival is measured from randomization until the subject has documented disease progression by an objective measure. Subjects were censored if no documented progression had occurred at the one year time point. Subjects must be alive with no more than 20% increase in tumor size to qualify for progression free survival. Changes in tumor size are defined by RECIST criteria.
Time frame: one year
Population: Intention to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amplimexon (Imexon) + Gemcitabine | Progression Free Survival | 2.8 months |
| Imexon Placebo + Gemcitabine | Progression Free Survival | 3.8 months |