Know Cancer

or
forgot password

A Phase Ib Multicenter Trial To Determine The Safety, Tolerance And Preliminary Antineoplastic Activity Of Gemcitabine Administered In Combination With Escalating Oral Doses Of OSI-774 To Patient Cohorts With Recently Diagnosed, Gemcitabine-Naive, Advanced Pancreatic Carcinoma Or Other Potentially Responsive Malignancies


Phase 1
18 Years
N/A
Not Enrolling
Both
Pancreatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

A Phase Ib Multicenter Trial To Determine The Safety, Tolerance And Preliminary Antineoplastic Activity Of Gemcitabine Administered In Combination With Escalating Oral Doses Of OSI-774 To Patient Cohorts With Recently Diagnosed, Gemcitabine-Naive, Advanced Pancreatic Carcinoma Or Other Potentially Responsive Malignancies


OBJECTIVES:

- Determine the maximum tolerated dose of erlotinib in combination with gemcitabine in
patients with recently diagnosed, gemcitabine-naive, locally advanced or metastatic
pancreatic carcinoma or other potentially responsive solid tumor.

- Determine the safety and tolerability of this regimen in these patients.

- Determine the pharmacokinetics of this regimen in these patients.

- Determine the objective antitumor response rate and response duration in patients
treated with this regimen.

- Determine the time to disease progression and duration of overall survival in patients
treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of erlotinib.

Patients receive gemcitabine IV over 30 minutes on day 1 of weeks 1-7 and oral erlotinib
once daily beginning on day 3 of week 1 and continuing for 8 weeks (course 1). Patients
receive subsequent courses of therapy comprising gemcitabine once weekly for 3 weeks and
erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or
unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 12 additional
patients are accrued and treated at the MTD as above.

Patients are followed at 30 days.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 3 months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed locally advanced or metastatic epithelial
carcinoma of the pancreas or other malignancy considered to be potentially responsive
to gemcitabine

- Newly diagnosed or gemcitabine naive

- Measurable or evaluable disease

- Not amenable to surgical intervention due to medical contraindications or
non-resectability of the tumor

- No islet cell tumors or other non-epithelial cell carcinomas of the pancreas

- No active CNS metastases or leptomeningeal disease

- Treated or asymptomatic brain metastases are allowed if on a stable dose of
corticosteroids and/or there is no change in brain disease status for at least 4
weeks after related therapy (e.g., whole-brain radiotherapy)

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Karnofsky 70-100%

Life expectancy:

- Not specified

Hematopoietic:

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- Bilirubin no greater than 2.0 mg/dL (except for documented Gilbert's syndrome)

- AST or ALT less than 2 times upper limit of normal (ULN) (no greater than 5 times ULN
if hepatic obstruction or metastases present)

- Albumin at least 2.5 g/dL

Renal:

- Creatinine less than 1.5 times ULN OR

- Creatinine clearance at least 60 mL/min

Cardiovascular:

- No significant cardiovascular disease

- No history of congestive heart failure currently requiring therapy

- No ventricular arrhythmia requiring anti-arrhythmic therapy

- No severe conduction disturbances

- No angina pectoris requiring therapy

- No myocardial infarction within the past 6 months

Gastrointestinal:

- No significant gastrointestinal abnormalities including:

- Requirement for IV alimentation

- Active peptic ulcer disease

Ophthalmic:

- No significant ophthalmologic abnormalities including:

- Severe dry eye syndrome

- Keratoconjunctivitis sicca

- Sjogren's syndrome

- Severe exposure keratopathy

- Disorders that would increase the risk for epithelium-related complications
(e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic
keratitis)

- Abnormal Schirmer test (less than 2 mm) allowed provided there is no evidence of
clinically significant corneal surface abnormalities

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No known or suspected hypersensitivity to gemcitabine

- No uncontrolled infection

- HIV negative

- No other malignancy within the past 5 years except treated non-melanoma skin cancer
or carcinoma in situ of the breast or cervix

- No other life-threatening illness

- No psychiatric disorders or altered mental status the would preclude informed consent
or study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 28 days since prior immunotherapy or biological response modified therapy
for the primary malignancy

- No concurrent immunotherapy or biologic response modifier therapy for the primary
malignancy

Chemotherapy:

- See Disease Characteristics

- At least 28 days since prior chemotherapy for the primary malignancy

- No prior mitomycin or nitrosoureas for the primary malignancy

- No more than 6 prior courses of chemotherapy with an alkylating agent for the primary
malignancy

- No prior gemcitabine for the primary malignancy except as a low-dose (less than 500
mg/m^2) radiosensitizer administered concurrently with or within 2 weeks after
radiotherapy at least 3 months ago

- No other concurrent chemotherapy for the primary malignancy

Endocrine therapy:

- See Disease Characteristics

- At least 28 days since prior systemic hormonal therapy (except LH-RH agonists) for
the primary malignancy

- No concurrent systemic hormonal therapy (except LH-RH agonists) for the primary
malignancy

- Other concurrent endocrine therapy is allowed as follows:

- Hormonal therapy (e.g., megestrol) for appetite stimulation

- Nasal, ophthalmic, or topical glucocorticoids

- Oral glucocorticoids for adrenal insufficiency

- Low-dose maintenance steroids

Radiotherapy:

- See Disease Characteristics

- At least 28 days since prior radiotherapy for the primary malignancy or metastases
and recovered

- No prior wide-field radiotherapy to 25% or more of marrow-bearing bone

- No prior pelvic irradiation

- No concurrent radiotherapy for the primary malignancy or metastases

- No concurrent wide-field radiotherapy for pain management

Surgery:

- See Disease Characteristics

- Recovered from any prior surgery

- No prior surgical procedures affecting absorption

Other:

- No prior agent for the primary malignancy targeting the epidermal growth factor
receptor (EGFR) or EGFR-specific tyrosine kinase activity

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Pedro Santabarbara, MD

Investigator Role:

Study Chair

Investigator Affiliation:

OSI Pharmaceuticals

Authority:

United States: Federal Government

Study ID:

OSI-774-155

NCT ID:

NCT00033241

Start Date:

June 2001

Completion Date:

April 2004

Related Keywords:

  • Pancreatic Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • stage II pancreatic cancer
  • stage III pancreatic cancer
  • recurrent pancreatic cancer
  • unspecified adult solid tumor, protocol specific
  • stage IV pancreatic cancer
  • Pancreatic Neoplasms

Name

Location

Arizona Cancer Center at University of Arizona Health Sciences CenterTucson, Arizona  85724
Cancer Therapy and Research CenterSan Antonio, Texas  78229