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A Phase I Study of Induction AMG 479 and Gemcitabine, Followed by AMG 479, Capecitabine, and 3D-Conformal Radiation Therapy (3D-CRT) With Subsequent Maintenance Therapy for Locally Advanced Pancreatic Cancer


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Pancreatic Cancer

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Trial Information

A Phase I Study of Induction AMG 479 and Gemcitabine, Followed by AMG 479, Capecitabine, and 3D-Conformal Radiation Therapy (3D-CRT) With Subsequent Maintenance Therapy for Locally Advanced Pancreatic Cancer


OBJECTIVES:

Primary

- To evaluate the maximum dose of ganitumab, up to a target dose of 20 mg/kg, given
concurrently with capecitabine and radiotherapy following induction ganitumab and
gemcitabine hydrochloride in patients with locally advanced pancreatic cancer.

Secondary

- To evaluate the safety profile of induction therapy comprising ganitumab and
gemcitabine hydrochloride, followed by ganitumab and concurrent chemoradiation, and
subsequently by maintenance ganitumab and gemcitabine hydrochloride until disease
progression in patients with locally advanced pancreatic cancer.

- To evaluate response and overall survival of patients treated at the maximum dose of
ganitumab given concurrently with capecitabine and radiotherapy following induction
ganitumab and subsequently followed by maintenance ganitumab and gemcitabine
hydrochloride until disease progression.

OUTLINE: This is a multicenter, dose-escalation study of ganitumab followed by an expanded
cohort study.

Induction therapy: Patients receive ganitumab IV over 1-2 hours on days 1 and 15 and
gemcitabine hydrochloride IV over 30 minutes on days 1, 15, and 22. Treatment repeats every
28 days for 2 courses.

Concurrent therapy: Beginning 10-28 days later, patients undergo 3-dimensional conformal
radiotherapy once daily, 5 days a week for 5.5 weeks beginning on day 1. Patients also
receive concurrent ganitumab IV over 1-2 hours on days 1, 15, and 29 and capecitabine orally
(PO) twice daily on days 1-5 weekly for 5.5 weeks.

Maintenance therapy: Beginning 21-42 days later, patients receive ganitumab IV over 1-2
hours on days 1 and 15 and gemcitabine hydrochloride IV over 30 minutes on days 1, 15, and
22. Courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years,
every 4 months for 1 year, and then annually thereafter.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Pathologically confirmed (histologic or cytologic) locally advanced adenocarcinoma of
the pancreas

- Patients must have unresectable disease based on institutional standardized
criteria of unresectability or medical inoperability

- Patients with or without regional adenopathy are eligible

- No distant metastases based upon the following minimum diagnostic workup:

- History and/or physical examination, including collection of weight and vital
signs, within 28 days prior to study entry

- Abdominal and/or pelvic CT scan with IV contrast or MRI scan within 21 days
prior to study entry

- Chest CT scan or whole-body PET/CT within 21 days prior to study entry

- No second malignancy or peritoneal seeding

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-1

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin (Hgb) ≥ 10.0 g/dL (the use of transfusion or other intervention to achieve
Hgb ≥ 10.0 g/dL is acceptable)

- Glycosylated hemoglobin (HgbA1c) ≤ 8%

- Serum creatinine ≤ 1.5 mg/dL

- ALT or AST < 3 times upper limit of normal (ULN)

- Total bilirubin < 3.0 mg/dL

- Alkaline phosphatase < 3 times ULN

- Fasting blood glucose < 160 mg/dL

- Patients with a non-fasting blood glucose > 160 mg/dL (8.9 mmol/L) must have a
fasting blood glucose ≤ 160 mg/dL (8.9 mmol/L) in order to be eligible

- No grade 2 or worse hearing impairment

- Negative serum pregnancy test (if applicable)

- Women of childbearing potential and men who are sexually active must be willing/able
to use medically acceptable forms of contraception during the course of the study,
and for 3 months (6 months for men) after the last study drug administration

- Not pregnant or nursing

- Ability to swallow oral medications

- At least 3 years since prior malignancy except non-melanomatous skin cancer or
carcinoma in situ of the breast, oral cavity, or cervix

- No severe active co-morbidity, defined as any of the following:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months

- Transmural myocardial infarction within 6 months prior to study entry

- Acute bacterial or fungal infection requiring intravenous antibiotics at the
time of registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization, or precluding study therapy within 30 days before
registration

- Uncontrolled malabsorption syndrome significantly affecting gastrointestinal
function

- Any unresolved bowel or bile duct obstruction

- Major resection of the stomach or small bowel that could affect the absorption
of capecitabine

- Acquired immune deficiency syndrome (AIDS) based upon current Centers for
Disease Control and Prevention (CDC) definition

- HIV testing is not required for entry into this protocol

- Existing venous thromboembolism requiring anti-coagulation therapy

- No prior allergic reaction to capecitabine or gemcitabine hydrochloride

PRIOR CONCURRENT THERAPY:

- No prior systemic chemotherapy for pancreatic cancer

- Prior chemotherapy for malignancies other than pancreatic cancer is allowed
provided chemotherapy was completed > 3 years prior to study entry

- No prior radiotherapy to the region of the study cancer that would result in overlap
of radiation therapy fields

- More than 28 days since any prior major surgery

- Insertion of a vascular access device, insertion of a biliary stent, exploratory
laparotomy, or laparoscopy are not considered major surgery

- No prior ganitumab

- Patients requiring concurrent oral anticoagulants (e.g., Coumadin, warfarin) are
eligible provided there is increased vigilance with respect to monitoring INR

- No concurrent participation in another clinical treatment trial

- No concurrent intensity-modulated radiotherapy

- No other concurrent therapy including the following:

- Other investigational or approved chemotherapeutic agents

- Other monoclonal antibody

- Sorivudine or brivudine A

- Cimetidine

- G-CSF agents

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity of ganitumab and capecitabine given concurrently with radiotherapy

Safety Issue:

Yes

Principal Investigator

Christopher H. Crane, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000695567

NCT ID:

NCT01298401

Start Date:

February 2012

Completion Date:

Related Keywords:

  • Pancreatic Cancer
  • adenocarcinoma of the pancreas
  • stage IIB pancreatic cancer
  • stage III pancreatic cancer
  • Pancreatic Neoplasms

Name

Location

CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
James Graham Brown Cancer Center at University of LouisvilleLouisville, Kentucky  40202
Rhode Island Hospital Comprehensive Cancer CenterProvidence, Rhode Island  02903
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
M. D. Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
Summa Center for Cancer Care at Akron City HospitalAkron, Ohio  44309-2090
McGlinn Family Regional Cancer Center at Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
St. Joseph Hospital Regional Cancer Center - OrangeOrange, California  92868-3849
Northmain Radiation OncologyProvidence, Rhode Island  02904