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)

NCT00107250 | Completed Phase 1 DMC

• 3 other identifiers: I171CAN-NCIC-IND171CDR0000422357
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; stage IV colon cancer; stage IV rectal cancer; unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity

  To recommend phase II dose of AZD2171 when given orally daily in combination with standard chemotherapy in patients with advanced NSCLC or colon cancer or other tumour types suitable for treatment with capecitabine.

  Each dose level

Secondary Outcomes (3)

• Safety

  Each dose level

• Anti-tumour activity

  Each dose level

• Tumour Response

  Each dose level

Study Arms (1)

AZD2171 + Standard chemotherpay regimens

EXPERIMENTAL

Drug: capecitabine; Drug: carboplatin; Drug: cediranib maleate; Drug: paclitaxel

Interventions

capecitabine 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.

AZD2171 + Standard chemotherpay regimens

carboplatin DRUG

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

AZD2171 + Standard chemotherpay regimens

cediranib maleate DRUG

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

AZD2171 + Standard chemotherpay regimens

paclitaxel DRUG

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

AZD2171 + Standard chemotherpay regimens

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed diagnosis of 1 of the following: * Non-small cell lung cancer (NSCLC) (closed to accrual as of 8/9/07) meeting 1 of the following stage criteria: * Stage IIIB disease * Patients without pleural effusion who are not candidates for combined modality treatment OR who were treated at centers where combined modality treatment is not considered standard treatment are eligible * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (2)

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• 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.

  PMID: 18398152 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Colonic Neoplasms; Rectal Neoplasms

Interventions

Capecitabine; Carboplatin; cediranib; Paclitaxel

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; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Derek Jonker, MD

  Ottawa Regional Cancer Centre

  STUDY CHAIR

• Scott A. Laurie, MD, FRCPC

  Ottawa Regional Cancer Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2005
• First Posted: April 6, 2005
• Study Start: January 21, 2005
• Primary Completion: October 23, 2009
• Study Completion: January 18, 2011
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)