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Study Summary
No. 2005-0999:.......Phase I Studies; Solid Tumors......Razelle Kurzrock......Phase I Program
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Study Summary Title
Study Summary
Number:
2005-0999
Study Title:A Phase I Dose-Finding Study of the Anti-Angiogenesis Agent, AG-013736, in Combinations of Paclitaxel/Carboplatin and Weekly Paclitaxel, Docetaxel, Capecitabine and Gemcitabine/Cisplatin in Patients with Advanced Solid Tumors
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Physician New Patient Referral
Name:Razelle KurzrockPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Phase I ProgramReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-794-1226
Contact us about clinical trials
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General Information
Disease Group:Phase I Studies
Solid Tumors
Supported By:N/A
Phase of Study:Phase IReturn
Visit:
Patients willl return to MDACC on Day 1 and 2 of Cycles 1 and 2, Days 1, 8 and
15 of each subsequent cycle, and 28 days after the last dose of AG-013736.
Treatment
Agents:
AG-013736
Capecitabine
Carboplatin
Cisplatin
Docetaxel
Gemcitabine
Paclitaxel
Home Care:n/a
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
Originally, the goal of this clinical research study was to find the highest
tolerable dose of AG-013736 that can be given with either paclitaxel and
carboplatin in combination, paclitaxel alone, docetaxel alone, capecitabine
alone, gemcitabine and cisplatin in combination in patients with advanced solid
tumors. The effects of AG-013736 on the tumor were also to be studied.
Enrollment has been completed for giving AG-013736 with paclitaxel alone,
docetaxel alone, capecitabine alone and gemcitabine/cisplatin.

The goal of this study now is to learn whether AG-013736 can be given in
combination with pemetrexed/cisplatin in solid tumors and
paclitaxel/carboplatin in squamous cell NSCLC. Researchers also want to learn
the highest tolerable dose of these combinations and the side effects that they
may cause.
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Study Objectives / Outcomes
Primary:
  • To determine the maximum tolerated doses (MTD) of AG-013736 in combination with
paclitaxel and carboplatin
  • To determine the MTD of AG-013736 in combination with weekly paclitaxel.
  • To determine the MTD of AG-013736 in combination with docetaxel.
  • To determine the MTD of AG-013736 in combination with capecitabine.
  • To determine the MTD of AG-013736 in combination with gemcitabine and cisplatin.

Secondary Objectives
  • To assess the dose limiting toxicity (DLT), overall safety and plasma pharmacokinetic (PK) profile of AG-013736, paclitaxel and carboplatin when given in combination.
  • To assess the overall safety profile of AG-013736, paclitaxel and carboplatin when given in combination in NSCLC patients with squamous cell histology.
  • To assess the DLT, overall safety profile and evaluate the plasma PK of AG-013736 and paclitaxel when given in combination.
  • To assess the DLT, overall safety profile and evaluate the plasma PK of AG-013736 and docetaxel when given in combination.
  • To assess the DLT, overall safety profile and evaluate the plasma PK of AG-013736 and capecitabine when given in combination.
  • To assess the DLT, overall safety profile and evaluate the plasma PK of AG-013736, gemcitabine and cisplatin when given in combination.
  • To assess response according to RECIST.
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Study Status Information
Study Activation / Registration Date:03/20/2007
IRB Review and Approval Date:06/07/2006
Study Type:Phase I
Recruitment Status:Terminated
Projected Accrual:approximately 70 patients
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Histologically or cytologically proven diagnosis of any advanced solid malignancy suitable for treatment with taxanes with or without carboplatin and capecitabine.

2) Expansion Cohort for AG-013736, paclitaxel and carboplatin combination: Histologically or cytologically proven diagnosis of NSCLC - squamous cell carcinoma. (Patients with mixed histology with predominantly squamous cell carcinoma are eligible)

3) No prior chemotherapy with platins (carboplatin, cisplatin, or oxaliplatin) or taxanes (paclitaxel, docetaxel, or paclitaxel protein-bound particles) for metastatic disease, except if: Adjuvant treatment with any of the above agents must have been completed greater than or equal to 12 months before enrollment, Patients in cohort 5 may not have received any previous cytotoxic chemotherapy for metastatic disease. Adjuvant chemo must have been completed greater than or equal to 12 months before enrollment, Patients in cohort 4, cohorts 6-7, and cohort 8 may have received any type of prior chemo.

4) At least 1 measurable disease or non-measureable disease.

5) Adults >/= 18 years of age

6) Life expectancy >/= 12 weeks

7) ECOG performance status 0 or 1

8) Resolution of all acute toxic effects of prior therapy or surgical procedure to grade </= 1 (except alopecia)

9) Adequate bone marrow function as defined by the following criteria: absolute neutrophil count (ANC) >/= 1500 cells/mm^3; platelets >/= 100,000 cells/mm^3; hemoglobin >/= 9.0 g/dL

10) Adequate liver function as defined by the following criteria (for patients receiving paclitaxel, carboplatin, cisplatin, gemcitabine or capecitabine): total serum bilirubin </= 1.5 times upper limit of normal (x ULN); AST/ALT </= 2.5 x ULN, or AST/ALT </= 5 X ULN if liver function abnormalities are due to underlying malignancy.

11) Adequate liver function as defined by the following criteria (for patients receiving docetaxel): total serum bilirubin </=1.0 times upper limit of normal (x ULN), AST/ALT </=1.5 x ULN

12) Adequate renal function as defined by the following criteria: serum creatinine </= 1.5 x ULN; </= 500 mg urinary protein/24 hours or dipstick < 2+

13) No evidence of pre-existing uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart (the baseline systolic blood pressure readings must be </= 140 mm Hg, and the baseline diastolic blood pressure readings must be </= 90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible)

14) Negative serum or urine pregnancy test within the 3 days before enrollment for women of child-bearing potential

15) Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial before enrollment.

16) Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:1) Prior irradiation to >/= 25% of the bone marrow (whole pelvis = 25%; a patient with prior whole pelvis irradiation is ineligible)

2) Prior radiation therapy, surgery, or treatment with an investigational agent within 4 weeks before treatment (Patients on LHRH analogs may be maintained on treatment)

3) One or more lung lesions with cavitation or any lesion invading and/or providing support for the wall of blood vessels (as assessed by CT and/or MRI)

4) Current use or anticipated need for drugs that are known CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine) during the course of the study.

5) Current use or anticipated need for drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St. John's wort) during the course of study (Note: the use of dexamethasone as a premedication for docetaxel or paclitaxel is not an exclusion criterion)

6) Requirement for therapeutic anticoagulant therapy including daily aspirin (>325 mg/day) or non-steroidal anti-inflammatory agents known to inhibit platelet function. Low-dose anticoagulants, such as low-dose heparin or 1-2 mg/day of coumadin for prevention of deep venous thrombosis or maintenance of patency of central venous access devices is permitted.

7) Patients with active seizure disorder or untreated brain metastases (Patients with clniical evidence suggestive of new brain metastases are excluded if brain metastases have not been ruled out via CT or MRI imaging. Patients with previously diagnosed brain metastases are eligible if they have completed their radiation therapy to the CNS and have recovered from the acute effects of that treatment before enrollment, have discontinued corticosteroid treatment for these metastases for at least 2 weeks, and are neurologically stable.)

8) Clinically significant gastrointestinal abnormalities including any of the following: inability to take oral medication; requiring intravenous alimentation; malabsorption syndromes; requiring treatment of active ulcer disease in the past 6 months; prior gastric resection; active gastrointestinal bleeding, related or unrelated to cancer, as evidenced by either hematemesis, hematochezia, or melena in the past 3 months

9) Any of the following within the 12 months before enrollment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack or pulmonary embolus.

10) NCI CTCAE Grade 3 hemorrhage from any cause < 4 weeks before enrollment

11) Hemoptysis > 1/2 teaspoon of blood per day within 1 week of enrollment

12) History of Grade 3 or 4 toxicity or severe hypersensitivity reaction associated with prior adjuvant treatment with paclitaxel, docetaxel, carboplatin, cisplatin, gemcitabine or capecitabine.

13) Prior allergic reaction to drugs containing Cremophor EL (for patients receiving paclitaxel) or polysorbate 80 (for patients receiving docetaxel)

14) Known human immunodeficiency virus (HIV) seropositivity

15) Women who are pregnant or breast feeding

16) Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator, would make the patient inappropriate for entry into this study.

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Links
Registration Number: NCT00454649
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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