AZD2171 + Chemotherapy in Advanced NSCLC, Colorectal Cancer, or Other Cancer Suitable for Treatment With Capecitabine (Non-Small Lung Cancer Patients Closed to Enrollment as 8/9/07)

NCT ID: NCT00107250

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-21
• Study Completion Date: 2011-01-18

Brief Summary

RATIONALE: AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, carboplatin, or capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving AZD2171 together with chemotherapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of AZD2171 when given together with chemotherapy in treating patients with advanced non-small cell lung cancer (closed to enrollment as of 8/9/07), colorectal cancer, or other cancer suitable to capecitabine treatment.

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose and recommended phase II dose of AZD2171 when administered in combination with standard chemotherapy comprising either paclitaxel and carboplatin OR capecitabine in patients with advanced incurable non-small cell lung cancer (closed to accrual as of 8/9/07), colorectal cancer, or other tumor types suitable for treatment with capecitabine.
• Determine the safety and tolerability of these regimens in these patients.
• Determine the toxicity profile and dose-limiting toxic effects of these regimens in these patients.
• Determine the pharmacokinetic profile of these regimens in these patients.
• Correlate the toxicity profile with the pharmacokinetic profile of these regimens in these patients.
• Determine the antitumor activity of these regimens in patients with measurable disease.
• Correlate patient outcome (response) with baseline (using tumor samples) and serial (using urine and plasma samples) biomarkers in patients treated with these regimens.

OUTLINE: This is an open-label, multicenter, dose-escalation study of AZD2171. Patients are assigned to 1 of 2 treatment groups according to diagnosis.

• Group 1 (non-small cell lung cancer) (closed to accrual as of 8/9/07): Patients receive paclitaxel IV and carboplatin IV on day 1. Patients also receive oral AZD2171 once daily on days 2-21 of course 1 and on days 1-21 of all subsequent courses. Treatment with paclitaxel and carboplatin repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Treatment with AZD2171 repeats every 21 days in the absence of disease progression or unacceptable toxicity.
• Group 2 (colorectal or other tumor types): Patients receive oral capecitabine twice daily on days 1-14. Patients also receive oral AZD2171 once daily on days 8-21 of course 1 and on days 1-21 of all subsequent courses. Treatment with capecitabine repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with AZD2171 repeats every 21 days in the absence of disease progression or unacceptable toxicity.

In both groups, patients achieving a complete response (CR) OR a stable partial response (SPR) receive 2 additional courses beyond CR or SPR.

Cohorts of 3-6 patients per group receive escalating doses of AZD2171 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 30 additional patients (20 in group 1 and 10 in group 2) will be treated at the MTD.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months until disease relapse.

PROJECTED ACCRUAL: A total of 3-35 patients will be accrued for this study.

Conditions

Colorectal Cancer; Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AZD2171 + Standard chemotherpay regimens

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

1000 mg/m2 orally twice daily (total of 2000 mg/m2 per day) for the first 14 days of a 21 day cycle for a maximum of 6-8 cycles.

carboplatin

Intervention Type: DRUG

AUC 6; IV; 30 minutes; Every 21 days for a maximum of 6-8 cycles

cediranib maleate

Intervention Type: DRUG

Given daily; orally with approximately 240 ml of water whilst in an upright position

paclitaxel

Intervention Type: DRUG

200mg/m2; IV; 3 hours; Every 21 days for a maximum of 6-8 cycles

Interventions

capecitabine

1000 mg/m2 orally twice daily (total of 2000 mg/m2 per day) for the first 14 days of a 21 day cycle for a maximum of 6-8 cycles.

Intervention Type: DRUG

carboplatin

AUC 6; IV; 30 minutes; Every 21 days for a maximum of 6-8 cycles

Intervention Type: DRUG

cediranib maleate

Given daily; orally with approximately 240 ml of water whilst in an upright position

Intervention Type: DRUG

paclitaxel

200mg/m2; IV; 3 hours; Every 21 days for a maximum of 6-8 cycles

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Stage IV disease
• Local or metastatic failure after prior surgery and/or radiotherapy
• Colorectal cancer

• Metastatic disease
• Considered suitable for first-line therapy with capecitabine
• Other tumor types

• Suitable for treatment with capecitabine
• No more than 2 prior chemotherapy regimens for advanced or metastatic disease
• Incurable by radiotherapy or surgery
• Clinically or radiologically documented disease

• No tumor marker elevation as the only evidence of disease
• No necrotic or hemorrhagic tumor or metastases
• No untreated brain or meningeal metastases

• Patients with previously treated stable brain metastases (by radiography or clinical exam) are eligible provided they are asymptomatic and do not require corticosteroids

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks (colorectal cancer patients)

Hematopoietic

• Hemoglobin adequate

• Anemia allowed provided patient is well compensated with no evidence of recent bleeding
• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No overt bleeding (i.e., ≥ 30 mL/episode) within the past 3 months

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT or AST ≤ 2 times ULN (5 times ULN for documented liver metastases)

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 50 mL/min
• No proteinuria > grade 1

Cardiovascular

• Resting systolic blood pressure ≤ 150 mm Hg AND/OR resting diastolic blood pressure ≤ 100 mm Hg (in the presence or absence of a stable dose of antihypertensive medication)
• Mean QTc ≤ 470 msec (with Bazetts correction) by ECG
• LVEF > 50% for patients with prior anthracyclines/trastuzumab or cardio-toxic agents
• No untreated or uncontrolled cardiovascular condition
• No symptomatic cardiac dysfunction
• No poorly controlled hypertension
• No history of labile hypertension
• No history of poor compliance with antihypertensive medication
• No history of familial long QT syndrome

Pulmonary

• No clinically relevant hemoptysis (i.e., ≥ 5 mL fresh blood) within the past 4 weeks

• Patients with only flecks of blood in their sputum are eligible

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective (double-method for females; barrier method for males) contraception
• No prior allergic reaction to drugs containing Cremophor EL® (NSCLC patients [closed to accrual as of 8/9/07])
• No peripheral neuropathy > grade 1 (NSCLC patients [closed to accrual as of 8/9/07])
• No dihydropyrimidine dehydrogenase deficiency (colorectal cancer patients)
• No history of severe hand-foot syndrome after treatment with fluoropyrimidines (colorectal cancer patients)
• No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or other curatively treated solid tumor
• No active or uncontrolled infection
• No other serious illness or medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior antiangiogenesis therapy

Chemotherapy

• At least 4 weeks since prior single-agent non-platinum-containing chemotherapy (6 weeks for nitrosoureas or mitomycin) for metastatic disease (NSCLC patients [closed to accrual as of 8/9/07])

• No more than 1 prior single-agent non-platinum-containing chemotherapy regimen for metastatic disease
• At least 6 months since prior adjuvant or neoadjuvant chemotherapy
• No prior taxane therapy (NSCLC patients [closed to accrual as of 8/9/07])
• No prior chemotherapy for metastatic disease (colorectal cancer patients)
• No prior capecitabine (colorectal cancer patients)

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior corticosteroids

Radiotherapy

• See Disease Characteristics
• At least 21 days since prior palliative radiotherapy except for low-dose non-myelosuppressive radiotherapy with approval
• At least 6 months since prior adjuvant radiotherapy

Surgery

• See Disease Characteristics
• At least 14 days since prior major surgery

Other

• Recovered from prior therapy
• At least 14 days since prior epidermal growth factor receptor inhibitor therapy
• Concurrent oral anticoagulants (e.g., warfarin) allowed provided INR is strictly monitored
• No other concurrent investigational therapy
• No other concurrent anticancer therapy
• No concurrent prophylactic pyridoxine (vitamin B_6) for hand-foot syndrome (colorectal or other tumor type patients)

• Use of pyridoxine after the onset of hand-foot syndrome allowed at the discretion of the physician

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Derek Jonker, MD

Role: STUDY_CHAIR

Ottawa Regional Cancer Centre

Scott A. Laurie, MD, FRCPC

Role: STUDY_CHAIR

Ottawa Regional Cancer Centre

Locations

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

Canada

References

Laurie SA, Gauthier I, Arnold A, Shepherd FA, Ellis PM, Chen E, Goss G, Powers J, Walsh W, Tu D, Robertson J, Puchalski TA, Seymour L. Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 2008 Apr 10;26(11):1871-8. doi: 10.1200/JCO.2007.14.4741.

Reference Type: RESULT

PMID: 18398152 (View on PubMed)

Other Identifiers

CAN-NCIC-IND171

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000422357

Identifier Type: OTHER

Identifier Source: secondary_id

I171

Identifier Type: -

Identifier Source: org_study_id