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Phase 2 Completed N=61 Randomized Treatment

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

Source: ClinicalTrials.gov NCT00460603 ↗
Enrolled (actual)
61
Serious AEs
44.0%
Results posted
Jun 2013
Primary outcomePrimary: Percentage of Participants With Objective Response: Phase 2 — 28.6; 48.8; 39.0 Percentage of participants — p=0.9726

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With Objective Response: Phase 2
28.6; 48.8; 39.0 0.9726
SECONDARY
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1
119.02; 106.76; 97.05; 95.70; 143.68; 117.47
SECONDARY
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1
190.51; 113.20; 205.41; 224.46; 168.07; 178.46
SECONDARY
Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1
35.57; 27.14; 24.23; 27.51; 42.48; 32.62
SECONDARY
Minimum Observed Plasma Trough Concentration (Cmin) For Axitinib: Phase 1
SECONDARY
Apparent Oral Clearance (CL/F) For Axitinib: Phase 1
30.01; 47.10; 28.49; 30.08; 33.33; 28.90
SECONDARY
Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1
3.26; 2.23; 3.47; 6.12; 3.09; 1.73
SECONDARY
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Oxaliplatin: Phase 1
4814.87; 4308.71; 5231.71; 5303.66
SECONDARY
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Oxaliplatin: Phase 1
5955.70; 5137.31; 6744.06; 6430.67
SECONDARY
Maximum Observed Plasma Concentration (Cmax) For Oxaliplatin: Phase 1
278.81; 265.05; 318.99; 374.03
SECONDARY
Minimum Observed Plasma Trough Concentration (Cmin) For Oxaliplatin: Phase 1
SECONDARY
Clearance (CL) For Oxaliplatin: Phase 1
27.51; 30.74; 24.29; 24.56
SECONDARY
Plasma Decay Half-Life (t1/2) For Oxaliplatin: Phase 1
20.63; 18.38; 23.30; 19.86
SECONDARY
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1
39212.03; 40955.29; 52164.28; 45087.71; 36533.84; 95123.13
SECONDARY
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1
36314.14; 41460.50; 52430.15; 38983.80; 36776.79; 96632.41
SECONDARY
Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1
16160.85; 34436.94; 19622.74; 16249.77; 39730.46; 34180.87
SECONDARY
Minimum Observed Plasma Trough Concentration (Cmin) For 5-Fluorouracil: Phase 1
SECONDARY
Clearance (CL) For 5-Fluorouracil: Phase 1
147.43; 128.28; 99.36; 137.34; 144.62; 53.92
SECONDARY
Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1
0.26; 0.19; 0.39; 0.25; 0.14; 0.24
SECONDARY
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Irinotecan: Phase 1
12081.58; 11496.32
SECONDARY
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Irinotecan: Phase 1
13055.88; 12459.89
SECONDARY
Maximum Observed Plasma Concentration (Cmax) For Irinotecan: Phase 1
1910.25; 1788.69
SECONDARY
Minimum Observed Plasma Trough Concentration (Cmin) For Irinotecan: Phase 1
SECONDARY
Clearance (CL) For Irinotecan: Phase 1
26.09; 27.34
SECONDARY
Plasma Decay Half-Life (t1/2) For Irinotecan: Phase 1
6.45; 6.75
SECONDARY
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Bevacizumab: Phase 1
3394758.83; 3554899.52
SECONDARY
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Bevacizumab: Phase 1
4987528.96; 5114888.84
SECONDARY
Maximum Observed Plasma Concentration (Cmax) For Bevacizumab: Phase 1
26460.05; 26850.12
SECONDARY
Minimum Observed Plasma Trough Concentration (Cmin) For Bevacizumab: Phase 1
SECONDARY
Clearance (CL) For Bevacizumab: Phase 1
0.01; 0.02
SECONDARY
Plasma Decay Half-Life (t1/2) For Bevacizumab: Phase 1
205.97; 210.22
SECONDARY
Duration of Response (DR): Phase 2
434.0; NA; 343.0
SECONDARY
Progression-Free Survival (PFS): Phase 2
336; 485; 381 0.5699
SECONDARY
Time to Treatment Failure (TTF): Phase 2
187.0; 241.0; 238.0 0.8884
SECONDARY
Overall Survival (OS): Phase 2
552.0; 659.0; 601.0 0.6904
SECONDARY
Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2
1.62; 2.20; 2.18; 0.63; 0.04; 0.80

Eligibility Criteria

Inclusion Criteria

  • (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.

Exclusion Criteria

  • 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00460603). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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