AZD2171 and Standard Combination Chemotherapy in Advanced Non-Small Cell Lung Cancer or Colorectal Cancer

NCIC Clinical Trials Group

Status and phase

Completed

Phase 1

Conditions

Lung Cancer

Colorectal Cancer

Treatments

Drug: leucovorin calcium

Drug: gemcitabine hydrochloride

Drug: fluorouracil

Drug: oxaliplatin

Drug: cisplatin

Drug: cediranib maleate

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00343408

CDR0000481443 (Other Identifier)

CAN-NCIC-IND175 (Other Identifier)

I175

Details and patient eligibility

About

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.

Full 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.

Enrollment

31 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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