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Randomized Phase II Clinical Trial of AZD6244 Hydrogen Sulfate (NSC-748727) and MK-2206 (NSC-749607) vs mFOLFOX in Patients With Metastatic Pancreatic Cancer After Prior Chemotherapy


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage IV Pancreatic Cancer

Thank you

Trial Information

Randomized Phase II Clinical Trial of AZD6244 Hydrogen Sulfate (NSC-748727) and MK-2206 (NSC-749607) vs mFOLFOX in Patients With Metastatic Pancreatic Cancer After Prior Chemotherapy


PRIMARY OBJECTIVES:

I. To assess overall survival in patients with metastatic pancreatic cancer treated with the
combination of AZD6244 hydrogen sulfate and MK-2206 compared to those treated with mFOLFOX.

II. To assess progression free survival (PFS) in patients with metastatic pancreatic cancer
treated with the combination of AZD6244 hydrogen sulfate and MK-2206 compared to those
treated with mFOLFOX.

SECONDARY OBJECTIVES:

I. To assess the frequency and severity of toxicity associated with the combination of
AZD6244 hydrogen sulfate and MK-2206 compared to those with mFOLFOX in this patient
population.

II. To assess objective tumor response in the subset of patients with measurable disease
(confirmed and unconfirmed complete and partial response) in patients with metastatic
pancreatic cancer treated with the combination of AZD6244 hydrogen sulfate and MK-2206
compared to those treated with mFOLFOX.

III. To bank tissue and blood for future translational medicine studies.

OUTLINE: This is a multicenter study. Patients are stratified according to duration of prior
systemic therapy line (=< 4 months vs > 4 months) and presence of liver metastasis (yes vs
no). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours on days 1 and 15 and
fluorouracil IV over 46-48 hours on days 1-2 and 15-16 (mFOLFOX).

ARM II: Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, 15, and 22, and
selumetinib PO daily on days 1-28.

In all arms, courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Blood and paraffin-embedded tumor tissue samples are collected for banking and future
correlative studies.

After completion of study treatment, patients are followed up periodically for 3 years.


Inclusion Criteria:



- Patients must have histologically or cytologically confirmed diagnosis of pancreatic
adenocarcinoma; patients with endocrine or neuroendocrine tumors, lymphoma of the
pancreas, or ampullary cancer are not eligible

- Patients must have distant metastatic disease; patients with macroscopic residual
disease post-resection as the only site of disease are not eligible; patients must
not have clinically significant ascites (defined as requiring paracentesis) or have
brain metastases

- Patients must have received one line, and no more than one line, of prior gemcitabine
chemotherapy for pancreatic cancer; for patients who received treatment for
advanced/metastatic disease, there must be documentation of disease progression while
on this treatment; for patients who received chemotherapy for treatment in the
adjuvant setting, recurrence to a metastatic site must be documented by imaging
studies within 6months of completing chemotherapy

- Patients must have measurable and/or non-measurable disease; x-rays, scans. or
physical examinations for assessment of measurable disease must have been completed
within 28 days prior to registration; x-rays, scans, or other tests for assessment of
non-measurable disease must have been completed within 42 days prior to registration;
all disease must be assessed and documented on the Baseline Tumor Assessment Form

- Sites must seek additional patient consent for the future use of specimens

- Zubrod performance status of 0-1

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count (ANC) >= 1,500/mcL

- Platelets >= 100,000/mcL

- Hemoglobin >= 9.0 g/dL

- Patients must have adequate kidney function as evidenced by at least ONE of the
following:

- Serum creatinine =< 1.5 mg/dL within 14 days prior to registration

- Calculated creatinine clearance >= 60 mL/min; the serum creatinine value used in
the calculation must have been obtained within 14 days prior to registration

- Total bilirubin =< 1.5 times institutional upper limit of normal(IULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 2.5 times
IULN

- Patients must have an albumin level >= 3.0 g/dL within 14 days prior to registration

- Patients must have an International Normalized Ratio (INR) =< 1.5 times IULN within
14 days prior to registration

- Patients must have an electrocardiogram (ECG) within 14 days prior to registration;
patients must have QTcF (by Fridericia's calculation) =< 450 msec (male) or =< 470
msec (female)

- Patients with baseline neuropathy must be =< grade 1 according to Common Terminology
Criteria for Adverse Events (CTCAE) v 4.0

- Patients must not have uncontrolled diarrhea or active infection requiring
antibiotics and be fully recovered from any previous serious infections within 7 days
prior to registration

- Patients must be able to swallow tablets and capsules

- Patients with diabetes must be well controlled with fasting glucose =< grade 1
according to CTCAE v 4.0 within 14 days prior to registration

- Patients with history of congestive heart failure must have an ejection fraction >=
55%within 14 days prior to registration

- Patients must not have any of the following: uncontrolled hypertension, acute
coronary syndrome within 6 months prior to registration, poorly controlled angina,
New York Heart Association Class II-IV heart failure, prior or current
cardiomyopathy, atrial fibrillation, or severe valvular heart disease

- Patients must not have a current or past history of central serous retinopathy,
retinal vein occlusion, retinal detachment, or have uncontrolled glaucoma
(irrespective of intraocular pressure [IOP])

- No prior malignancy is allowed except for the following: adequately treated basal
cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage
I or II cancer from which the patient is currently in complete remission, or any
other cancer from which the patient has been disease-free for five years

- Patients must not be pregnant or nursing due to unknown fetal and infant risks;
women/men of reproductive potential must have agreed to use an effective
contraceptive method during the study plus at least 16 weeks after last dose; a woman
is considered to be of "reproductive potential" if she has had menses at any time in
the preceding 12 consecutive months; in addition to routine contraceptive methods,
"effective contraception" also includes heterosexual celibacy and surgery intended to
prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a
hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any
point a previously celibate patient chooses to become heterosexually active during
the time period for use of contraceptive measures outlined in the protocol, he/she is
responsible for beginning contraceptive measures

- Patients must have completed systemic therapy at least 28 days prior to registration,
any surgical procedure must have been performed at least 14 days prior to
registration, and radiation therapy must be completed at least 7 days prior to
registration; patients must have recovered from any of the effects of prior therapies
or procedures

- Patients must not plan to receive concurrent chemotherapy, radiotherapy, laxatives,
agents known to prolong QTc interval, or agents known to be potent to Cytochrome P450
CYP3A4/5 (CYP3A4/5) or Cytochrome P450 1A2 (CYP1A2)

- Patients must not have received prior treatment with leucovorin calcium,
fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX), FOLFOX, MEK
inhibitors, PI3K inhibitors, or AKT inhibitors

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Time Frame:

From date of registration to death due to any cause using the long-rank test, assessed up to 3 years

Safety Issue:

No

Principal Investigator

Vincent Chung

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01993

NCT ID:

NCT01658943

Start Date:

August 2012

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Pancreas
  • Recurrent Pancreatic Cancer
  • Stage IV Pancreatic Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Pancreatic Neoplasms

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Louisiana State University New Orleans, Louisiana  70112-2282
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Borgess Medical Center Kalamazooaa, Michigan  49001
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Cancer Center of Kansas - Chanute Chanute, Kansas  66720
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Mercy Hospital Coon Rapids, Minnesota  55433
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Fox Valley Hematology and Oncology Appleton, Wisconsin  54911
Highland General Hospital Oakland, California  94602
Northeast Georgia Medical Center Gainesville, Georgia  30501
Miami Valley Hospital Dayton, Ohio  45409
Cancer Center of Kansas - Fort Scott Fort Scott, Kansas  66701
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Knox Community Hospital Mount Vernon, Ohio  43050
Wenatchee Valley Medical Center Wenatchee, Washington  98801-2028
Marshfield Clinic Cancer Care at Regional Cancer Center Eau Claire, Wisconsin  54701
Saint Joseph's Hospital Marshfield, Wisconsin  54449
Marshfield Clinic - Weston Center Weston, Wisconsin  54476
Diagnostic and Treatment Center Weston, Wisconsin  54476
Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids, Wisconsin  54494
Rocky Mountain Oncology Casper, Wyoming  82609
Genesys Regional Medical Center Grand Blanc, Michigan  48439-8066
Greene Memorial Hospital Xenia, Ohio  45385
Harold Alfond Center for Cancer Care Augusta, Maine  04330
Union Hospital of Cecil County Elkton MD, Maryland  21921
Sherman Hospital Elgin, Illinois  60120-2198
Memorial Medical Center Springfield, Illinois  62781
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Englewood Hospital and Medical Center Englewood, New Jersey  07631
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Queen's Medical Center Honolulu, Hawaii  96813
Vanderbilt University Nashville, Tennessee  37232-6305
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Contra Costa Regional Medical Center Martinez, California  94553-3156
Larry G Strieff MD Medical Corporation Oakland, California  94609
Tahoe Forest Cancer Center Truckee, California  96161
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University of Rochester Rochester, New York  14642
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Saint Alphonsus Regional Medical Center Boise, Idaho  83706
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Doctors Medical Center- JC Robinson Regional Cancer Center San Pablo, California  94806
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Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
Middlesex Hospital Middletown, Connecticut  06457
Edna Williams Cancer Center at the Baptist Cancer Institute Jacksonville, Florida  32207
Saint Joseph's-Candler Health System Savannah, Georgia  31405
Oncare Hawaii Inc-POB II Honolulu, Hawaii  96813
Oncare Hawaii Inc-Kuakini Honolulu, Hawaii  96817
University of Hawaii Honolulu, Hawaii  96813
Joliet Oncology-Hematology Associates Limited Joliet, Illinois  60435
Good Samaritan Regional Medical Center Mt. Vernon, Illinois  62864
Saint Francis Hospital and Health Centers Beech Grove, Indiana  46107
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard Fort Wayne, Indiana  46845
Reid Hospital and Health Care Services Richmond, Indiana  47374
Hematology Oncology Associates-Quad Cities Bettendorf, Iowa  52722
Genesis Medical Center - East Campus Davenport, Iowa  52803
Mercy Medical Center-Sioux City Sioux City, Iowa  51104
Saint Luke's Regional Medical Center Sioux City, Iowa  51104
Cancer Center of Kansas - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas-Kingman Kingman, Kansas  67068
Cancer Center of Kansas - Parsons Parsons, Kansas  67357
Cancer Center of Kansas - Pratt Pratt, Kansas  67124
Cancer Center of Kansas-Wichita Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas - Main Office Wichita, Kansas  67214
Ochsner Clinic Foundation-Baton Rouge Baton Rouge, Louisiana  70809
DeSoto Regional Health System Mansfield, Louisiana  71052
Louisiana State University Sciences Center- Monroe Monroe, Louisiana  71210
Ochsner Clinic CCOP New Orleans, Louisiana  70121
Highland Clinic Shreveport, Louisiana  71105
Hickman Cancer Center Adrian, Michigan  49221
Michigan Cancer Research Consortium Community Clinical Oncology Program Ann Arbor, Michigan  48106
Oakwood Hospital Dearborn, Michigan  48123
Saint John Hospital and Medical Center Detroit, Michigan  48236
Allegiance Health Jackson, Michigan  49201
Sparrow Hospital Lansing, Michigan  48912
Saint Mary Mercy Hospital Livonia, Michigan  48154
Mercy Memorial Hospital Monroe, Michigan  48162
Saint Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Saint Joseph Mercy Port Huron Port Huron, Michigan  48060
Saint Mary's of Michigan Saginaw, Michigan  48601
Lakeland Hospital St. Joseph, Michigan  49085
Saint John Macomb-Oakland Hospital Warren, Michigan  48093
Unity Hospital Fridley, Minnesota  55432
Saint John's Hospital - Healtheast Maplewood, Minnesota  55109
Minnesota Oncology Hematology PA-Maplewood Maplewood, Minnesota  55109
North Memorial Medical Health Center Robbinsdale, Minnesota  55422
Saint Cloud Hospital Saint Cloud, Minnesota  56303
Park Nicollet Clinic - Saint Louis Park Saint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-Woodbury Woodbury, Minnesota  55125
Saint Louis-Cape Girardeau CCOP Saint Louis, Missouri  63141
Missouri Baptist Medical Center Saint Louis, Missouri  63131
Saint John's Mercy Medical Center Saint Louis, Missouri  63141
Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield Springfield, Missouri  65802
Saint John's Hospital Springfield, Missouri  65804
Cox Medical Center Springfield, Missouri  65807
Hematology-Oncology Centers of the Northern Rockies PC Billings, Montana  59101
Saint Vincent Healthcare Billings, Montana  59101
Billings Clinic Billings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment Center Butte, Montana  59701
Benefis Healthcare- Sletten Cancer Institute Great Falls, Montana  59405
Saint Peter's Community Hospital Helena, Montana  59601
Saint Patrick Hospital - Community Hospital Missoula, Montana  59802
Good Samaritan Hospital Kearney, Nebraska  68847
Nevada Cancer Research Foundation CCOP Las Vegas, Nevada  89106
Cooper Hospital University Medical Center Camden, New Jersey  08103
Veterans Adminstration New Jersey Health Care System East Orange, New Jersey  07018-1095
Orange Regional Medical Center Middletown, New York  10940
Wayne Memorial Hospital Goldsboro, North Carolina  27534
Kinston Medical Specialists PA Kinston, North Carolina  28501
Saint Alexius Medical Center Bismarck, North Dakota  58501
Summa Barberton Hospital Barberton, Ohio  44203
Doctors Hospital Columbus, Ohio  43228
Grant Medical Center Columbus, Ohio  43215
Mount Carmel Health Center West Columbus, Ohio  43222
Good Samaritan Hospital - Dayton Dayton, Ohio  45406
Dayton CCOP Dayton, Ohio  45429
Samaritan North Health Center Dayton, Ohio  45415
Hematology Oncology Center Incorporated Elyria, Ohio  44035
Blanchard Valley Hospital Findlay, Ohio  45840
Atrium Medical Center-Middletown Regional Hospital Franklin, Ohio  45005-1066
Kettering Medical Center Kettering, Ohio  45429
Saint Rita's Medical Center Lima, Ohio  45801
Marietta Memorial Hospital Marietta, Ohio  45750
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center Maumee, Ohio  43537
Saint Charles Hospital Oregon, Ohio  43616
Toledo Community Hospital Oncology Program CCOP Toledo, Ohio  43617
Mercy Cancer Center at Saint Anne Mercy Hospital Toledo, Ohio  43623
University of Toledo Toledo, Ohio  43614
Saint Vincent Mercy Medical Center Toledo, Ohio  43608
Upper Valley Medical Center Troy, Ohio  45373
Saint Ann's Hospital Westerville, Ohio  43081
Genesis HealthCare System Zanesville, Ohio  43701
Natalie W Bryant Cancer Center Tulsa, Oklahoma  74136
Legacy Good Samaritan Hospital and Medical Center Portland, Oregon  97210
Sanford Cancer Center-Oncology Clinic Sioux Falls, South Dakota  57104
The Don and Sybil Harrington Cancer Center Amarillo, Texas  79106
Fredericksburg Oncology Inc Fredericksburg, Virginia  22401
Harrison Bremerton Hematology and Oncology Bremerton, Washington  98310
Columbia Basin Hematology and Oncology PLLC Kennewick, Washington  99336
Minor and James Medical PLLC Seattle, Washington  98104
Swedish Medical Center-First Hill Seattle, Washington  98122-4307
Sacred Heart Hospital Eau Claire, Wisconsin  54701
Saint Mary's Hospital Green Bay, Wisconsin  54303
Dean Hematology and Oncology Clinic Madison, Wisconsin  53717
Marshfield Clinic-Minocqua Center Minocqua, Wisconsin  54548
Oconomowoc Memorial Hospital-ProHealth Care Inc Oconomowoc, Wisconsin  53066-3896
Marshfield Clinic at James Beck Cancer Center Rhinelander, Wisconsin  54501
Marshfield Clinic-Rice Lake Center Rice Lake, Wisconsin  54868
Saint Michael's Hospital Stevens Point, Wisconsin  54481
Marshfield Clinic-Wausau Center Wausau, Wisconsin  54401
University of California Medical Center At Irvine-Orange Campus Orange, California  92868
Roger Maris Cancer Center Fargo, North Dakota  58122
Elkhart Clinic Elkhart, Indiana  46515
Michiana Hematology Oncology PC-Elkhart Elkhart, Indiana  46514
Michiana Hematology Oncology PC-Plymouth Plymouth, Indiana  46563
Michiana Hematology Oncology PC-South Bend South Bend, Indiana  46601
Michiana Hematology Oncology-PC Westville Westville, Indiana  46391
Cancer Center of Kansas-Liberal Liberal, Kansas  67901
University of Michigan University Hospital Ann Arbor, Michigan  48109
UMDNJ - New Jersey Medical School Newark, New Jersey  07103
Community Health Partners Regional Medical Center Elyria, Ohio  44035
Erlanger Medical Center Chattanooga, Tennessee  37403
Skagit Valley Hospital Mt. Vernon, Washington  98273
Evergreen Hematology and Oncology PS Spokane, Washington  99218
West Virginia University Charleston Charleston, West Virginia  25304
Marshfield Clinic-Chippewa Center Chippewa Falls, Wisconsin  54729
Marshfield Clinic Cancer Care at Saint Michael's Hospital Stevens Point, Wisconsin  54481
State University of New York Downstate Medical Center Brooklyn, New York  11203
Texas Tech University Health Sciences Center Lubbock, Texas  79430
Kaiser Permanente Los Angeles Medical Center Los Angeles, California  90027
FirstHealth of the Carolinas-Moore Regional Hosiptal Pinehurst, North Carolina  28374
Kaiser Anaheim Medical Center Anaheim, California  92807
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Kaiser Foundation Hospital Bellflower, California  90706
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Kaiser Permanente Moanalua Medical Center Honolulu, Hawaii  96819
Capital Region Medical Center-Goldschmidt Cancer Center Jefferson City, Missouri  65109
Saint John's Clinic-Rolla-Cancer and Hematology Rolla, Missouri  65401
Kings County Hospital Brooklyn, New York  11203
The Mark H Zangmeister Center Columbus, Ohio  43219
Southern Ohio Medical Center Portsmouth, Ohio  45662
Cancer Care Center at Island Hospital Anacortes, Washington  98221
Highline Medical Center-Main Campus Burien, Washington  98166
United General Hospital Sedro-Woolley, Washington  98284
Legacy Salmon Creek Hospital Vancouver, Washington  98686
Gundersen Lutheran La Crosse, Wisconsin  54601
Central Indiana Cancer Centers - Indianapolis Indianapolis, Indiana  46227
Kaiser Permanente-Franklin Denver, Colorado  80205
Siouxland Hematology Oncology Associates Sioux City, Iowa  51101
Swedish Cancer Institute-Issaquah Issaquah, Washington  98029
Marshfield Clinic - Ladysmith Center Ladysmith, Wisconsin  54848
Alta Bates Summit Medical Center-Herrick Campus Berkeley, California  94704
Michiana Hematology Oncology PC-Mishawaka Mishawaka, Indiana  46545-1470
Marie Yeager Cancer Center Saint Joseph, Michigan  49085
Sanford Clinic North-Fargo Fargo, North Dakota  58102
Sanford Medical Center-Fargo Fargo, North Dakota  58122
Summa Akron City Hospital Akron, Ohio  44304
Franciscan St. Francis Health Indianapolis, Indiana  46237
The Toledo Hospital/Toledo Children's Hospital Toledo, Ohio  43606
Sanford USD Medical Center - Sioux Falls Sioux Falls, South Dakota  57117-5134
Sanford Clinic North-Bemidgi Bemidji, Minnesota  56601
Sanford Bismarck Medical Center Bismarck, North Dakota  58501
Toledo Clinic Cancer Centers-Oregon Oregon, Ohio  43616
Community Howard Regional Health Kokomo, Indiana  46904
Indiana University Health La Porte Hospital La Porte, Indiana  46350
Saint Joseph Regional Medical Center-Mishawaka Mishawaka, Indiana  46545-1470
PeaceHealth Saint Joseph Medical Center Bellingham, Washington  98225
Christiana Care Health System-Christiana Hospital Newark, Delaware  19718
Springfield Regional Medical Center Springfield, Ohio  45505
Saint Louis Cancer and Breast Institute-South City Saint Louis, Missouri  63109
Toledo Clinic Cancer Centers-Bowling Green Bowling Green, Ohio  43402
Toledo Clinic Cancer Centers-Maumee Maumee, Ohio  43537-1839
Toledo Clinic Cancer Centers-Toledo Toledo, Ohio  43623
Guthrie Clinic-Robert Packer Hospital Sayre, Pennsylvania  18840
Harrison Poulsbo Hematology and Oncology Poulsbo, Washington  98370
Sutter Pacific Medical Foundation Santa Rosa, California  95403
OnCare Hawaii-Liliha Honolulu, Hawaii  96817-3169
Ochsner Baptist Medical Center New Orleans, Louisiana  70115
Cancer Center of Western Wisconsin New Richmond, Wisconsin  54017
Saint Clare's Hospital Weston, Wisconsin  54476
Oncare Hawaii Inc - Kapiolani Medical Center at Pali Momi Aiea, Hawaii  96701
D N Greenwald Center Mukwonago, Wisconsin  53149
Swedish Medical Center-Edmonds Edmonds, Washington  98026
Idaho Urologic Institute PA Meridian, Idaho  83642
Kaiser Permanente-Modesto Modesto, California  95356