Clinical trial NCT00343408: AZD2171 and Standard Combination Chemotherapy in Advanced Non-Small Cell Lung Cancer or Colorectal Cancer
Official title: A Phase I, Open-Label, Dose-Seeking Study of AZD2171 Given Daily Orally in Combination With Selected Standard Chemotherapy Regimens (CT) in Patients With Advanced Incurable Non-Small Cell Lung Cancer (NSCLC) or Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Cancer
Lung Cancer
Keywords: recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent colon cancer
stage III colon cancer
stage IV colon cancer
recurrent rectal cancer
stage III rectal cancer
stage IV rectal cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2006-06-23
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: AZD2171 may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy 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 standard combination 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 standard combination chemotherapy in treating patients with advanced non-small cell lung cancer (NSCLC) or colorectal cancer.

Detailed description: OBJECTIVES:

* Determine the recommended phase II dose of AZD2171 when administered with standard combination chemotherapy in patients with advanced non-small cell lung cancer or colorectal cancer.
* Determine the safety, tolerability, toxicity profile, dose-limiting toxicities, and pharmacokinetic profile of this treatment regimen.
* Assess the antitumor activity of this treatment regimen in patients with measurable disease.
* Correlate the toxicity profile with pharmacokinetics.

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

* Group 1 (non-small cell lung cancer): Patients receive gemcitabine hydrochloride IV on days 1 and 8 and cisplatin IV on day 1. Patients also receive oral AZD2171 once daily beginning on day 2. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
* Group 2 (colorectal cancer): Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Patients also receive oral AZD2171 once daily beginning on day 3. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

In both groups, cohorts of 3-6 patients receive escalating doses of AZD2171 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

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

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed diagnosis of 1 of the following:

  * Non-small cell lung cancer (NSCLC), meeting 1 of the following criteria:

    * Stage IIIB disease

      * No pleural effusion and not a candidate for a combined modality treatment
    * Stage IV disease
    * Local or metastatic failure after surgery and/or radiotherapy
  * Colorectal cancer (CRC)

    * Advanced and/or metastatic disease
    * Suitable for first-line therapy with oxaliplatin, leucovorin calcium, and fluorouracil (FOLFOX-6)
* Clinically or radiologically documented disease

  * No tumor marker elevation as sole evidence of disease
* No necrotic/hemorrhagic metastases or tumor
* No untreated brain or meningeal metastases

  * Previously treated, radiologic or clinical evidence of stable brain metastases allowed provided disease is asymptomatic and corticosteroids are not required

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Hemoglobin normal
* Absolute granulocyte count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 50 mL/min
* Bilirubin ≤ 1.5 times ULN
* AST or ALT ≤ 2 times ULN (5 times ULN if liver involvement)
* Proteinuria ≤ grade 1
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No history of other malignancies except adequately treated nonmelanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
* No untreated and/or uncontrolled cardiovascular conditions or symptomatic cardiac dysfunction
* No resting blood pressure (BP) consistently higher than systolic BP \> 150 mm Hg and diastolic BP \> 100 mm Hg (in the presence or absence of a stable dose of antihypertensive medication)
* No poorly controlled hypertension, history of labile hypertension, or poor compliance with antihypertensive medication
* No overt bleeding (≥ 30 mL bleeding/episode) within the past 3 months
* No clinically relevant hemoptysis (≥ 5 mL fresh blood) within the past 4 weeks

  * Flecks of blood in sputum allowed
* No active or uncontrolled infections
* No serious illnesses or medical conditions that would preclude compliance with study requirements
* No mean QTc with Bazett's correction \> 470 msec
* No history of familial long QT syndrome
* No peripheral neuropathy \> grade 1
* No dihydropyrimidine dehydrogenase deficiency or history of severe hand-foot syndrome after fluoropyrimidines (for patients with CRC)

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Recovered from prior therapy
* At least 6 months since prior adjuvant or neoadjuvant therapy
* At least 6 months since prior adjuvant radiotherapy
* At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C) (for patients with NSCLC)
* At least 4 weeks since prior and no concurrent corticosteroids
* At least 3 weeks since prior palliative radiotherapy and recovered

  * Concurrent palliative radiotherapy allowed
* At least 2 weeks since prior epidermal growth factor receptor inhibitor therapy
* At least 2 weeks since prior major surgery
* No more than 1 prior single-agent, nonplatinum-containing chemotherapy regimen for metastatic disease (for patients with NSCLC)
* No prior gemcitabine hydrochloride (for patients with NSCLC)
* No prior oxaliplatin (for patients with CRC)
* No prior angiogenesis inhibitor
* No prior chemotherapy for advanced/metastatic disease (for patients with CRC)
* No other concurrent experimental drugs or anticancer therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital - Montreal
state: Quebec
Study officials:
affiliation: Jewish General Hospital
name: Gerald Batist, MD
role: STUDY_CHAIR
affiliation: Princess Margaret Hospital, Canada
name: Eric X. Chen, MD, PhD
role: STUDY_CHAIR
affiliation: Ottawa Regional Cancer Centre
name: Glenwood D. Goss, MD, BCh, FCP, FRCPC
role: STUDY_CHAIR
References:
citation: Chen E, Jonker D, Gauthier I, MacLean M, Wells J, Powers J, Seymour L. Phase I study of cediranib in combination with oxaliplatin and infusional 5-Fluorouracil in patients with advanced colorectal cancer. Clin Cancer Res. 2009 Feb 15;15(4):1481-6. doi: 10.1158/1078-0432.CCR-08-0761.