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Phase I-II Study of Avastin®+ Bortezomib for Patients With Recurrent or Refractory Non-Squamous NSCLC


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Lung Cancer

Thank you

Trial Information

Phase I-II Study of Avastin®+ Bortezomib for Patients With Recurrent or Refractory Non-Squamous NSCLC


Bortezomib is designed to enter cells and interfere with a substance found inside cells that
is responsible for allowing cells to divide.

Avastin® is designed to prevent or slow down the growth of cancer cells by blocking the
growth of blood vessels.

If you are found to be eligible to take part in this study, depending on when you enroll,
you will be assigned to one of up to 4 treatment groups. There will be 3 participants in
each of the first few groups, and an additional 30 participants in the last group. The
first few (2 or 3) groups are part of the first phase of the study, and the last group (3rd
or 4th) is part of the second phase. All participants will receive the same dose level of
Avastin®. The amount of bortezomib you receive will depend on when you enroll in the study.
The exact dose of bortezomib that you receive will be based on your height and weight. In
the first phase of the study, groups of participants will be assigned to one of 2 bortezomib
dose levels. The first group will receive the highest dose. The next groups will receive
either that same dose level, or if intolerable side effects occurred, a lower dose level.
For the second part of the study, the last group will receive the highest dose level that
did not cause intolerable side effects in the other groups.

A cycle of treatment is 3 weeks (21 days). Bortezomib will be given once a week for the
first 2 weeks of each cycle. Avastin® will be given every 3 weeks. (On Day 1 of each
cycle, you will receive both bortezomib and Avastin®.)

Bortezomib will be injected through a needle in your vein. Each injection will last about
3-5 seconds. After receiving each dose of bortezomib, the clinic staff will check how well
you are tolerating the drug. During that time, you will be asked about any side effects you
may be experiencing. Your doctor may decrease or pause the dose of bortezomib if you
experience certain side effects.

Avastin® will be given as an infusion through a needle in your vein, over 90 minutes. If
you tolerate the 90-minute infusion well, the second infusion will be given over 60 minutes.
If you tolerate the 60-minute infusion well, all following infusions will be given over 30
minutes. If you do not tolerate the shorter infusion time, future infusion times will be
increased until a tolerable level is reached.

Every 3 weeks, you will have a physical exam, including measurement of vital signs and
weight. Blood (about 2 teaspoons) will be drawn for routine tests. You will have a
performance status evaluation. On Day 8 of each cycle of treatment, blood (about 2
teaspoons) will be drawn for routine tests. The level of protein in your urine will be
monitored at least every 6 weeks.

You may continue receiving study treatment for as long as the cancer responds to the
treatment or for up to 1 year. Your doctor may decide to take you off this study if you
experience intolerable side effects or your health gets worse.

After you have stopped taking the study treatment, you will have a physical exam, including
measurement of vital signs. Blood (about 2 teaspoons) will be drawn for routine tests. You
will have a performance status evaluation, chest x-ray, and a CT or MRI scan. On an
indefinite basis, the study nurse will contact you by telephone from time to time to see how
you are doing.

This is an investigational study. Bortezomib has been FDA approved and it is registered in
Europe for the treatment of multiple myeloma patients who have received at least one prior
therapy. Avastin® has been FDA approved for the treatment of metastatic colorectal cancer
and non-small cell lung cancer. However, bortezomib and Avastin® are not FDA-approved for
this type of cancer, and they have been authorized for use together in research only. Up to
42 patients will take part in this study. All will be enrolled at M. D. Anderson.


Inclusion Criteria:



1. Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.

2. Female subject is either post-menopausal (Postmenopausal women must be amenorrheic
for at least 12 months to be considered of non-childbearing potential) or surgically
sterilized or willing to use an acceptable method of birth control (i.e. a hormonal
contraceptive, intra-uterine device, diaphragm with spermicide, condom with
spermicide, or abstinence) for the duration of the study. Male subject agrees to use
an acceptable method for contraception for the duration of the study.

3. All patients must have an Eastern Cooperative Oncology Group (ECOG)Performance Status
of 0 - 2

4. Patients must have histologically or cytologically proven selected Stage IIIB (T4
lesion due to malignant pleural or pericardial effusion) or Stage IV advanced
non-small cell lung cancer or recurrent disease after previous surgery and/or
radiation.

5. No history of or active brain metastases

6. Patients must have measurable disease documented by computed tomography (CT) or
magnetic resonance imaging (MRI). Measurable disease must be assessed within 28 days
prior to registration. Pleural effusions, ascites and laboratory parameters are not
acceptable as the only evidence of disease.

7. Recurrent or progressive cancer can be within a previously radiated site

8. Patients must have received one or two prior systemic therapies, one of which
contained a platinum compound. No prior Bortezomib or antiangiogenic agent is
permitted. Prior radiation is permitted; however, at least two weeks must have
elapsed since the completion of prior radiation therapy and patients must have
recovered from all associated toxicities at the time of registration. At least two
weeks must have elapsed since surgery (thoracic or other major surgeries) and
patients must have recovered from all associated toxicities at the time of
registration.

9. Patients must have a serum creatinine (i.e. 1.5 mg/dL) AND a creatinine clearance >/= 40 cc/min determined by either urine
collection and testing or calculation using the following formula: Calculated
Creatinine Clearance = (140 - age) * Weight(kg) * (0.85 if female)/ 72 * creatinine
(mg/dL)

10. Patients must have an Absolute neutrophil count (ANC)>/= 2,000/µl and platelet count
>/= 100,000/µl obtained within 28 days prior to registration. Hemoglobin: >9.0 *
10^9/L

11. Patients must have adequate hepatic function documented by a serum bilirubin institutional upper limit of normal (1.0) and liver enzymes (serum glutamic
oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT)) 3.0 * the institutional upper limit of normal obtained within 28 days prior to
registration

12. Peripheral neuropathy, if present, must be < Grade 2 (NCI Common Terminology Criteria
for Adverse Events Version 3.0).

13. Patients known to be HIV-positive and taking HAART therapy are not eligible due to
possible pharmacokinetic interactions

14. Patients must not be planning to receive any other concomitant anticancer treatment
including chemotherapy, radiation therapy, biologic agents or any other
investigational drugs

15. Patient must be >/= 18 years of age.

16. Patients must be informed of the investigation nature of this study and must sign and
give written informed consent in accordance with institutional and federal
guidelines.

Exclusion Criteria:

1. Patients meeting any of the following exclusion criteria are not to be enrolled in
the study. Participation in an experimental drug study within 4 weeks of the first
treatment on this trial: Blood pressure > 140/90 mm Hg, History of stroke within 6
months, Clinically significant peripheral vascular disease, Evidence of bleeding
diathesis or coagulopathy, Presence of central nervous system or brain metastases

2. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, or anticipation of need for major surgical procedure during the
course of the study.

3. Minor surgical procedures such as fine needle aspirations or core biopsies within 7
days prior to Day 0

4. Urine protein: creatinine ratio >/= 1.0 at screening

5. Serious non-healing wound, ulcer, or bone fracture

6. Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) Class II or heart failure, unstable angina, severe uncontrolled
ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active
conduction system abnormalities. Prior to study entry, and ECG abnormality at
Screening has to be documented by the investigator as not medically relevant

7. Patients with squamous histology

8. Patients with hematemesis or more than ½ teaspoon of hemoptysis within 6 months of
study entry.

9. Patients requiring full dose oral or parenteral anticoagulation.

10. Abdominal fistula, GI perforation, or abdominal abscess within the last 6 months

11. Patient has hypersensitivity to boron or mannitol

12. Female subject is pregnant or breast-feeding. Confirmation that the subject is not
pregnant must be established by a negative serum beta-human chorionic gonadotropin
(beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
required for post-menopausal or surgically sterilized women. Patient has received
other investigational drugs within 28 days before enrollment

13. Serious medical or psychiatric illness likely to interfere with participation in this
clinical study

14. No other prior or concurrent malignancy is allowed except for: non-melanoma skin
cancers, in situ cervical cancer, and any cancer from which the patient has been
disease-free for 3 years or more.

15. Pregnant or nursing women may not participate in this trial because of the increased
risk of fetal harm including fetal death from the chemotherapeutic agents. Women/men
of reproductive potential may not participate unless they have agreed to use an
effective contraceptive method.

16. Patients requiring treatment with Nonsteroidal anti-inflammatory drugs (NSAIDS),
antiplatelet agents, or aspirin > 325 mg/day

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

MTD is defined as the highest dose level in which 6 patients have been treated with 2 patients with dose limiting toxicity (DLT).

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

Bonnie S. Glisson, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2006-0045

NCT ID:

NCT00411593

Start Date:

November 2006

Completion Date:

May 2007

Related Keywords:

  • Lung Cancer
  • Non-Small Cell Lung Cancer
  • Lung Cancer
  • NSCLC
  • Bortezomib
  • Bevacizumab
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

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