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Colorectal CancerPhase 1NCT00107250

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)

A Phase 1 study testing capecitabine, carboplatin and cediranib maleate in people with Colorectal Cancer and Lung Cancer, run by NCIC Clinical Trials Group at 2 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 120 years
What is being tested?
capecitabine, carboplatin and cediranib maleate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
2 sitesCanada
Study dates
21 Jan 2005to 18 Jan 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

2 sites in 1 country.

Canada2 sites
  • Ottawa Hospital Regional Cancer Centre - General Campus

    Ottawa, Ontario, K1H 8L6

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase I, Open-Label, Dose-Seeking Study of AZD2171 Given Daily Orally in Combination With Standard Chemotherapy Regimens (CT) in Patients With Advanced Incurable Non-Small Cell Lung Cancer (NSCLC) or Colorectal Cancer or Other Tumor Types Suitable for Treatment With Capecitabine

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.

Read the 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.

Being tested
capecitabine, carboplatin, cediranib maleate, paclitaxel
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
Medical subject headings
Colorectal Neoplasms, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • capecitabineDrug

    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.

  • carboplatinDrug

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

  • cediranib maleateDrug

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

  • paclitaxelDrug

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

Study groups in NCT00107250
Study groupRoleWhat they receive
AZD2171 + Standard chemotherpay regimensExperimentalNot described
Receives: Drug: capecitabine; Drug: carboplatin; Drug: cediranib maleate; Drug: paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Each dose level

Secondary outcomes (3)
  1. Safety

    safety, tolerability, toxicity profile, dose limiting toxicities and pharmacokinetic profile of AZD2171 and standard chemotherapy given in these combinations. The correlation, if any,between the toxicity profile and the pharmacokinetics will be determined.

    Measured: Each dose level

  2. Anti-tumour activity

    Assessing the anti-tumour activity of AZD2171 in combination with standard chemotherapy regimens in patients with measurable disease.

    Measured: Each dose level

  3. Tumour Response

    To correlate patient outcomes (response) with baseline (tumour) and serial (urine and plasma) biomarkers

    Measured: Each dose level

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Apr 2005 (estimated)
  2. Study start21 Jan 2005
  3. Primary completion23 Oct 2009
  4. Study completion18 Jan 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00107250
Sponsor's protocol ID
I171
Other IDs
CAN-NCIC-IND171, CDR0000422357
Status last verified
Apr 2020
First submitted
5 Apr 2005
Last updated
4 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 18398152

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing capecitabine, carboplatin and cediranib maleate in people with Colorectal Cancer and Lung Cancer, run by NCIC Clinical Trials Group at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity (time frame: Each dose level). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00107250, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023.

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