Clinical trial NCT00376948: Genistein, Gemcitabine, and Erlotinib in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
Official title: Phase II Trial of Novasoy®, Gemcitabine, and Erlotinib in Locally Advanced or Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas
stage III pancreatic cancer
stage IV pancreatic cancer
recurrent pancreatic cancer
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-09-15
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Patients Alive
timeFrame: at 6 months
measure: Median Overall Survival Estimate
timeFrame: up to 17 months
Secondary outcomes:
measure: Overall Objective Response Rate (Complete and Partial Response)
timeFrame: Every 8 weeks
measure: Response Duration
timeFrame: Every 8 weeks
measure: Time to Treatment Failure
timeFrame: Every 8 weeks
measure: Time to Progression
timeFrame: Every 8 weeks
measure: Grade 3 or Higher Toxicity Evaluation
timeFrame: First day of each cycle
measure: pAKT (Pichia Anomala Killer Toxin) and NF (Nuclear Factor)-kappaB Activation
timeFrame: At start of study
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Khaldoun Almhanna, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Barbara Ann Karmanos Cancer Institute
name: Fazlul H. Sarkar, PhD
role: PRINCIPAL_INVESTIGATOR
References: