Pancreatic Cancer
Conditions
Keywords
adenocarcinoma of the pancreas, stage III pancreatic cancer, stage IV pancreatic cancer, recurrent pancreatic cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Genistein may help gemcitabine and erlotinib kill more tumor cells by making tumor cells more sensitive to the drugs. PURPOSE: This phase II trial is studying how well giving genistein together with gemcitabine and erlotinib works in treating patients with locally advanced or metastatic pancreatic cancer.
Detailed description
OBJECTIVES: Primary * Determine the 6-month survival rate of patients with locally advanced or metastatic pancreatic cancer treated with genistein, gemcitabine hydrochloride, and erlotinib hydrochloride. Secondary * Determine the frequency of objective tumor response rate in these patients. * Determine the time to treatment failure in these patients. * Determine the effect of baseline expression of pAKT and activation of NF-kappaB on survival of patients treated with this regimen. * Determine the overall time to disease progression in these patients. * Estimate the quantitative and qualitative toxicities of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive oral genistein twice daily on days -7 to 28 in course 1 and on days 1-28 in all other courses. Patients also receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and oral erlotinib hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Interventions
DIETARY_SUPPLEMENTgenistein
DRUGerlotinib hydrochloride
DRUGgemcitabine hydrochloride
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed pancreatic adenocarcinoma * Locally advanced or metastatic disease by radiological evidence * Must have biopsy material consisting of 10 unstained slides or paraffin-embedded tissue blocks available for correlative studies * No endocrine tumor or lymphoma of the pancreas * No history of CNS (central nervous system) metastases PATIENT CHARACTERISTICS: * SWOG (Southwest Oncology Group) performance status 0-1 * Life expectancy ≥ 12 weeks * Platelet count ≥ 100,000/mm\^3 * Absolute neutrophil count ≥ 1,500/mm\^3 * Bilirubin \< 2.0 mg/dL * AST (aspartate aminotransferase) and ALT (alanine aminotransferase) \< 1.5 times upper limit of normal * Creatinine \< 1.5 mg/dL * Albumin \> 2.5 g/dL * INR (international normalized ratio) \< 1.3 (in the absence of ongoing treatment with warfarin) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active infection * No condition that would limit the ability to receive oral medications * No requirement for a gastrostomy tube for the administration of drugs * No serious concurrent systemic disorder, that, in the opinion of the investigator, is incompatible with the study * No active second primary malignancy within the past year except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin * No allergy to any study drug PRIOR CONCURRENT THERAPY: * No prior chemotherapy or radiotherapy for metastatic disease * Prior adjuvant chemotherapy allowed provided it was completed at least 6 months ago * No prior gemcitabine hydrochloride or epidermal growth factor receptor-inhibiting agents * No other concurrent chemotherapy, immunotherapy, tumor-directed hormonal therapy, or radiotherapy * No other concurrent investigational agents * No other concurrent antitumor therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Patients Alive | at 6 months |
| Median Overall Survival Estimate | up to 17 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Treatment Failure | Every 8 weeks | Imaging tests (CT scan, CXR, MRI or imaging studies as clinically indicated). Progressive disesase is defined as a greater than 20% increase in the sum of the longest diameter of target lesions taking as reference the smalles sum of the longest diameter recorded since the treatment started or the appearance of new lesions. |
| Time to Progression | Every 8 weeks | Imaging tests (CT scan, CXR, MRI or imaging studies as clinically indicated). Progressive disesase is defined as a greater than 20% increase in the sum of the longest diameter of target lesions taking as reference the smalles sum of the longest diameter recorded since the treatment started or the appearance of new lesions. |
| Overall Objective Response Rate (Complete and Partial Response) | Every 8 weeks | Imaging tests (CT scan, CXR \[Chest X-Ray\], MRI or imaging studies as clinically indicated |
| pAKT (Pichia Anomala Killer Toxin) and NF (Nuclear Factor)-kappaB Activation | At start of study | Tumor tissue collected from paraffin |
| Grade 3 or Higher Toxicity Evaluation | First day of each cycle | Toxicity evaluation using NCI-CTC (Common Terminology Criteria) v.3 criteria; CBC (complete blood count) with differential white cell and platelet counts; Serum sodium, potassium, chloride, bicarbonate, AST, ALT, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine, and albumin; Serum CA 19-9 |
| Response Duration | Every 8 weeks | Imaging tests (CT scan, CXR, MRI or imaging studies as clinically indicated). Progressive disesase is defined as a greater than 20% increase in the sum of the longest diameter of target lesions taking as reference the smalles sum of the longest diameter recorded since the treatment started or the appearance of new lesions. Partial response is defined as greater than or equal to 30% reduction in the sum of the longest diameteres of target lesions, taking as reference the baseline sum of the longest diameters. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Novasoy®, Gemcitabine & Erlotinib Novasoy® 396 mg (177 mg of Isoflavones) twice-daily starting daay -7 until day 28; Gemcitabine 1000 mg/m2 days 1, 8, & 15; Erlotinib 150 mg day 1 until day 28
genistein
erlotinib hydrochloride
gemcitabine hydrochloride | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Novasoy®, Gemcitabine & Erlotinib |
|---|---|
| Age, Continuous | 58.5 years |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 20 |
| serious Total, serious adverse events | 14 / 20 |
Outcome results
Primary
Median Overall Survival Estimate
Time frame: up to 17 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Novasoy®, Gemcitabine & Erlotinib | Median Overall Survival Estimate | 6.3 months |
Primary
Patients Alive
Time frame: at 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novasoy®, Gemcitabine & Erlotinib | Patients Alive | 10 participants |
Secondary
Grade 3 or Higher Toxicity Evaluation
Toxicity evaluation using NCI-CTC (Common Terminology Criteria) v.3 criteria; CBC (complete blood count) with differential white cell and platelet counts; Serum sodium, potassium, chloride, bicarbonate, AST, ALT, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine, and albumin; Serum CA 19-9
Time frame: First day of each cycle
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Novasoy®, Gemcitabine & Erlotinib | Grade 3 or Higher Toxicity Evaluation | fatigue | 5 Participants |
| Novasoy®, Gemcitabine & Erlotinib | Grade 3 or Higher Toxicity Evaluation | other toxicity | 4 Participants |
| Novasoy®, Gemcitabine & Erlotinib | Grade 3 or Higher Toxicity Evaluation | diarrhea | 3 Participants |
| Novasoy®, Gemcitabine & Erlotinib | Grade 3 or Higher Toxicity Evaluation | infection | 1 Participants |
| Novasoy®, Gemcitabine & Erlotinib | Grade 3 or Higher Toxicity Evaluation | nausea | 7 Participants |
| Novasoy®, Gemcitabine & Erlotinib | Grade 3 or Higher Toxicity Evaluation | neutrophil | 4 Participants |
| Novasoy®, Gemcitabine & Erlotinib | Grade 3 or Higher Toxicity Evaluation | pain | 5 Participants |
| Novasoy®, Gemcitabine & Erlotinib | Grade 3 or Higher Toxicity Evaluation | platelet | 1 Participants |
| Novasoy®, Gemcitabine & Erlotinib | Grade 3 or Higher Toxicity Evaluation | stomach mucostis | 1 Participants |
| Novasoy®, Gemcitabine & Erlotinib | Grade 3 or Higher Toxicity Evaluation | vomiting | 4 Participants |
| Novasoy®, Gemcitabine & Erlotinib | Grade 3 or Higher Toxicity Evaluation | wbc | 2 Participants |
Secondary
Overall Objective Response Rate (Complete and Partial Response)
Imaging tests (CT scan, CXR \[Chest X-Ray\], MRI or imaging studies as clinically indicated
Time frame: Every 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novasoy®, Gemcitabine & Erlotinib | Overall Objective Response Rate (Complete and Partial Response) | 0.056 proportion of patients |
Secondary
pAKT (Pichia Anomala Killer Toxin) and NF (Nuclear Factor)-kappaB Activation
Tumor tissue collected from paraffin
Time frame: At start of study
Population: Data not collected
Secondary
Response Duration
Imaging tests (CT scan, CXR, MRI or imaging studies as clinically indicated). Progressive disesase is defined as a greater than 20% increase in the sum of the longest diameter of target lesions taking as reference the smalles sum of the longest diameter recorded since the treatment started or the appearance of new lesions. Partial response is defined as greater than or equal to 30% reduction in the sum of the longest diameteres of target lesions, taking as reference the baseline sum of the longest diameters.
Time frame: Every 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Novasoy®, Gemcitabine & Erlotinib | Response Duration | 73 days |
Secondary
Time to Progression
Imaging tests (CT scan, CXR, MRI or imaging studies as clinically indicated). Progressive disesase is defined as a greater than 20% increase in the sum of the longest diameter of target lesions taking as reference the smalles sum of the longest diameter recorded since the treatment started or the appearance of new lesions.
Time frame: Every 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Novasoy®, Gemcitabine & Erlotinib | Time to Progression | 2.07 moths |
Secondary
Time to Treatment Failure
Imaging tests (CT scan, CXR, MRI or imaging studies as clinically indicated). Progressive disesase is defined as a greater than 20% increase in the sum of the longest diameter of target lesions taking as reference the smalles sum of the longest diameter recorded since the treatment started or the appearance of new lesions.
Time frame: Every 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Novasoy®, Gemcitabine & Erlotinib | Time to Treatment Failure | 2.04 months |