Study With AG-013736 Combined With Chemotherapy And Bevacizumab In Patients With Metastatic Colorectal Cancer

NCT00460603 | Completed Phase 1 Results

• 1 other identifier: A4061020
• Study Type: interventional
• Target: 187
• Locations: 1 country
• Sites: 106

Brief Summary

To determine the safety and efficacy of AG-013736 in combination with other standard of care medication in patients with first line metastatic colorectal cancer.

Conditions

Colorectal Neoplasms

Keywords

GI neoplasms (phase 1)

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Objective Response: Phase 2

  Percentage of participants with objective response (OR) based assessment of confirmed complete response(CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all lesions and no appearance of new lesions. Confirmed PR defined as \>=30 percent (%) decrease in sum of the longest dimensions (LD) of the target lesions taking as reference the baseline sum LD , without progression of nontarget lesions and no appearance of new lesions. Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response.

  Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy)

Secondary Outcomes (35)

• Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1

  Predose, 1, 2, 2.5, 4, 6 and 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1

• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1

  Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1

• Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1

  Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1

• Minimum Observed Plasma Trough Concentration (Cmin) For Axitinib: Phase 1

  Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1

• Apparent Oral Clearance (CL/F) For Axitinib: Phase 1

  Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1

Study Arms (3)

B

ACTIVE COMPARATOR

bevacizumab 5 mg/kg every 2 weeks + FOLFOX

Drug: bevacizumab

C

EXPERIMENTAL

AG-013726 5 mg bid+ bevacizumab 2 mg/kg every 2 weeks + FOLFOX

Drug: AG-013726

A

EXPERIMENTAL

AG-013736 5 mg bid starting dose + FOLFOX

Drug: AG-013736 (axitinib)

Interventions

bevacizumab DRUG

bevacizumab 5 mg/kg every 2 weeks

B

AG-013726 DRUG

AG-013726 5 mg bid every 2 weeks

C

AG-013736 (axitinib) DRUG

AG-013736 5 mg bid starting dose

A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (Phase 1) Patients with any solid/GI tumor who have had no more than 1 previous chemotherapy for greater than 3 months prior to enrollment
• (Phase 2) Patients with locally advanced or metastatic colorectal cancer (CRC) previously untreated with any systemic therapy.
• Patients treated with adjuvant chemotherapy (with radiation) will be eligible if last treatment was \> 12 months prior to enrollment,
• Patients must have measurable disease by RECIST and if any history of hypertension, it must be controlled with medication.

You may not qualify if:

• Prior system therapy for advanced CRC (Ph 2 portion only)
• Prior treatment with anti-angiogenesis agent such as bevacizumab or VEGF inhibitors.
• Prior irradiation of greater than 25% of bone marrow (whole pelvis = 25%)
• Prior radiation, major surgery, or investigational agent within 4 weeks of study entry except palliative radiotherapy to non-target, metastatic lesions. Minor surgeries should be completed \> 2 weeks of enrollment and be fully recovered from any procedure.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (106)

Pfizer Investigational Site

Daphne, Alabama, 36526, United States

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Huntsville, Alabama, 35801, United States

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Huntsville, Alabama, 35805, United States

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Mobile, Alabama, 36608, United States

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Antioch, California, 94531, United States

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Colton, California, 92324, United States

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Corona, California, 92879, United States

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Gilroy, California, 95020, United States

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Glendora, California, 91741, United States

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La Jolla, California, 92037, United States

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La Jolla, California, 92093, United States

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Pasadena, California, 91105, United States

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Pleasant Hill, California, 94523, United States

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Pomona, California, 91767, United States

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Rancho Cucamonga, California, 91730, United States

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Rancho Mirage, California, 92270, United States

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Redlands, California, 92374, United States

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San Diego, California, 92103, United States

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San Diego, California, 92121, United States

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San Leandro, California, 94578, United States

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West Covina, California, 91790, United States

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Auroa, Colorado, 80012, United States

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Boulder, Colorado, 80303, United States

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Colorado Springs, Colorado, 80909, United States

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Denver, Colorado, 80218, United States

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Denver, Colorado, 80220, United States

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Lakewood, Colorado, 80228, United States

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Littleton, Colorado, 80120-4413, United States

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Lone Tree, Colorado, 80124, United States

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Longmont, Colorado, 80501, United States

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Parker, Colorado, 80138, United States

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Thornton, Colorado, 80260, United States

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Ocala, Florida, 34471, United States

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Stuart, Florida, 34994, United States

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Atlanta, Georgia, 30318, United States

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Beech Grove, Indiana, 46107, United States

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Indianapolis, Indiana, 46237, United States

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Jeffersonville, Indiana, 47130, United States

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Muncie, Indiana, 47303, United States

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Kansas City, Kansas, 66112, United States

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Overland Park, Kansas, 66210, United States

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Louisville, Kentucky, 40202, United States

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Louisville, Kentucky, 40207, United States

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Louisville, Kentucky, 40217, United States

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Louisville, Kentucky, 40241, United States

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Shelbyville, Kentucky, 40065, United States

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Baton Rouge, Louisiana, 70809, United States

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Brownstone, Michigan, 48183, United States

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Dearborn, Michigan, 48126, United States

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Detroit, Michigan, 48202, United States

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West Bloomfield, Michigan, 48322, United States

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Kansas City, Missouri, 64111, United States

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Kansas City, Missouri, 64131, United States

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Kansas City, Missouri, 64154, United States

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Lee's Summit, Missouri, 64064, United States

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St Louis, Missouri, 63110, United States

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Grand Island, Nebraska, 68803, United States

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Las Vegas, Nevada, 89135, United States

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Summit, New Jersey, 07902, United States

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Albany, New York, 12206, United States

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Albany, New York, 12208, United States

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Amsterdam, New York, 12010, United States

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Hudson, New York, 12534, United States

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Latham, New York, 12110-0610, United States

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Rexford, New York, 12148, United States

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Troy, New York, 12180, United States

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Kernersville, North Carolina, 27284, United States

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Lexington, North Carolina, 27295, United States

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Mount Airy, North Carolina, 27030, United States

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North Wilkesboro, North Carolina, 28659, United States

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Pollocksville, North Carolina, 28573, United States

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Winston-Salem, North Carolina, 27103, United States

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Oregon City, Oregon, 97045, United States

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Portland, Oregon, 97213, United States

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Portland, Oregon, 97225, United States

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Portland, Oregon, 97227, United States

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Tualatin, Oregon, 97062, United States

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West Reading, Pennsylvania, 19611, United States

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Charleston, South Carolina, 29406, United States

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Easley, South Carolina, 29640, United States

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Greenville, South Carolina, 29605, United States

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Greenville, South Carolina, 29615, United States

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Seneca, South Carolina, 29672, United States

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Spartanburg, South Carolina, 29307, United States

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Chattanooga, Tennessee, 37403, United States

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Franklin, Tennessee, 37067, United States

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Gallatin, Tennessee, 37066, United States

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Hermitage, Tennessee, 37076, United States

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Lebanon, Tennessee, 37087, United States

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Nashville, Tennessee, 37203, United States

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Nashville, Tennessee, 37205, United States

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Nashville, Tennessee, 37207, United States

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Pfizer Investigational Site

Nashville, Tennessee, 37211, United States

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Smyrna, Tennessee, 37167, United States

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Dallas, Texas, 75235, United States

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Dallas, Texas, 75237, United States

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Dallas, Texas, 75246, United States

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Dallas, Texas, 75390, United States

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Fort Worth, Texas, 76177, United States

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Houston, Texas, 77090, United States

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Tyler, Texas, 75702, United States

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Ogden, Utah, 84403-3274, United States

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Everett, Washington, 98201, United States

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Kennewick, Washington, 99336, United States

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Pfizer Investigational Site

Vancouver, Washington, 98684, United States

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Pfizer Investigational Site

Vancouver, Washington, 98686, United States

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Related Publications (2)

• Hoh CK, Burris HA 3rd, Bendell JC, Tarazi J, Rosbrook B, Kim S, Infante JR, Reid TR. Intermittent dosing of axitinib combined with chemotherapy is supported by (18)FLT-PET in gastrointestinal tumours. Br J Cancer. 2014 Feb 18;110(4):875-81. doi: 10.1038/bjc.2013.806. Epub 2014 Jan 14.

  PMID: 24423921 DERIVED

• Infante JR, Reid TR, Cohn AL, Edenfield WJ, Cescon TP, Hamm JT, Malik IA, Rado TA, McGee PJ, Richards DA, Tarazi J, Rosbrook B, Kim S, Cartwright TH. Axitinib and/or bevacizumab with modified FOLFOX-6 as first-line therapy for metastatic colorectal cancer: a randomized phase 2 study. Cancer. 2013 Jul 15;119(14):2555-63. doi: 10.1002/cncr.28112. Epub 2013 Apr 19.

  PMID: 23605883 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Axitinib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Time to Treatment Failure (TTF) was included as a secondary endpoint of the study after change in analysis plan.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2007
• First Posted: April 16, 2007
• Study Start: January 1, 2006
• Primary Completion: April 1, 2012
• Study Completion: November 1, 2012
• Last Updated: December 6, 2013
• Results First Posted: June 4, 2013

Record last verified: 2013-11

Locations

US (106)