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A Modular Phase I-II Trial of Lenalidomide and Paclitaxel in Men With Castration-Resistant Prostate Cancer and Lymph-Node Dominant Metastases


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Male
Prostate Cancer

Thank you

Trial Information

A Modular Phase I-II Trial of Lenalidomide and Paclitaxel in Men With Castration-Resistant Prostate Cancer and Lymph-Node Dominant Metastases


Study Drugs:

Lenalidomide is a drug that changes the immune system and it may also interfere with the
development of tiny blood vessels that help support tumor growth. Taking lenalidomide could
prevent the growth of cancer cells.

Paclitaxel is designed to disrupt the growth of cancer cells, which may cause cancer cells
to die.

Phases I and II:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you joined the study. Up to 10 groups of 3 participants will be
enrolled in the Phase I portion of the study, and 1 group of up to 42 participants will be
enrolled in Phase II.

If you are enrolled in the Phase I portion, the doses of lenalidomide you receive will
depend on when you joined this study. The dose of paclitaxel will be the same for all
patients. Up to 5 dose levels of lenalidomide will be tested in the Phase I portion. The
first group of Phase I participants will receive the lower doses of lenalidomide. Each new
group enrolled will receive the higher doses, if no intolerable side effects were seen.
Groups will continue being enrolled (up to 10) until the highest tolerable dose of
lenalidomide (in combination with paclitaxel) is found.

If you are enrolled in the Phase II portion, you will receive lenalidomide at the highest
dose that was tolerated in the Phase I portion in combination with paclitaxel.

Study Drug Administration:

Once you are assigned a dose, you will take lenalidomide capsules by mouth once a day for 21
days in a row, followed by 7 days of rest (Days 22-28). This will be called the "lead-in"
period."

You will the begin taking lenalidomide and paclitaxel on 28 day study cycles. You will take
lenalidomide by mouth every day on Days 1-21 of each cycle. Paclitaxel will be given by
vein over 1 hour on Days 1, 8, and 15 of each cycle. On Days 22-28 of each cycle, you will
take no study drugs. The Day 1 dose of Lenalidomide in each combination cycle may occur
within +/- 5 days of the Day 1 paclitaxel dose.

You should swallow lenalidomide capsules whole with water at the same time each day. Do not
break, chew, or open the capsules.

If you miss a dose of lenalidomide, take it as soon as you remember on the same day.

If you miss taking your dose for the entire day, take your regular dose the next scheduled
day (do NOT take double your regular dose to make up for the missed dose).

If you take more than the prescribed dose of lenalidomide you should seek emergency medical
care, if needed, and contact study staff right away.

Females of childbearing potential that might be caring for you should not touch the
lenalidomide capsules or bottles unless they are wearing gloves.

In order to participate in this study you must also register into and follow the
requirements of the RevAssist® program of Celgene Corporation. This program provides
education and counseling on the risks of fetal exposure, blood clots, and reduced blood
counts. You will be required to receive counseling every 28 days during treatment with
lenalidomide, follow the birth control requirements of the program that are appropriate for
you, and take telephone surveys about your compliance with the program.

Study Visits:

On Day 1 of each cycle (before you receive paclitaxel), the following tests and procedures
will be performed:

- You will have a physical exam, including measurement of your weight.

- Your performance status will be recorded.

- You will be asked about any drugs or treatments you may be receiving.

- Blood (about 2-3 teaspoons) will be drawn for routine tests and tests of your PSA and
testosterone levels.

- You will be asked about any side effects you may have experienced since your last
visit.

On Days 8 and 15 of each cycle (before you receive paclitaxel), the following tests and
procedures will be performed:

- Your weight will be measured.

- Blood (about 2 teaspoons) will be drawn for routine tests.

On Day 1 of Cycle 3 and every 2 cycles thereafter, you will have the following tests and
procedures performed:

- You will have a chest x-ray and a CT scan of your abdomen and pelvis to check the
status of the disease.

- Blood (about 2 teaspoons) will be drawn to test your testosterone level and your liver
function.

- You will have a bone scan to check the status of the disease.

- You will have an ECG.

If you are being treated with paclitaxel at your local oncologist's office, you are only
required to return to M. D. Anderson on Days 1 and 15 of Cycle 1 and on Day 1 of each cycle
after that. All other study visits may be done at your local oncologist's office.

Length of Study:

You will continue on this study as long as you are benefiting. You will be removed from the
study if you experience intolerable side effects, if the disease gets worse, or if the study
doctor thinks it is in your best interest.

End-of-Study Visit:

Once you are off study, the following tests and procedures will be performed:

- You will have a physical exam.

- Blood (about 3-4 teaspoons) will be drawn for routine tests and tests of your PSA and
testosterone levels.

- You will be asked about any side effects you may have experienced since your last
visit.

- Your performance status will be recorded.

This is an investigational study. Lenalidomide is approved by the Food and Drug
Administration (FDA) and commercially available for the treatment of specific types of
myelodysplastic syndrome (MDS) and in combination with dexamethasone for patients with
multiple myeloma (MM) who have received at least 1 prior therapy. Paclitaxel is FDA-approved
and commercially available for the treatment of bladder cancer, lung cancer, breast cancer,
and pancreatic cancer. The use of these drugs in combination is investigational.

Up to 72 participants will take part in this study. All will be enrolled at M. D. Anderson.


Inclusion Criteria:



1. Patients with metastatic adenocarcinoma of the prostate

2. Patients in Phase II must have radiographic evidence of multiple (>/= 2) or bulky
(>/= 5cm diameter) lymph node metastases with < 2 bone (on radionucleotide bone scan)
discrete sites of involvement.

3. Patient must have had front-line chemotherapy for castrate-resistant metastatic
disease. Any number of prior chemotherapy regimens is permitted, except within the
last 3 weeks. No prior thalidomide or lenalidomide therapy is permitted.

4. Patients must have evidence of progression of disease based on any one of the
following criteria: a) PSA- progression is defined as 2 consecutive increments in PSA
(with an absolute change of at least 1ng/mL) over 4 weeks. b) An increase by 25% of
the product of bi-dimensional disease or 30% in maximum diameter or appearance of an
unequivocally new lesion qualifies as progression. c) Worsening symptoms clearly
attributable to disease progression qualifies as progression e.g. worsening malignant
bony pain.

5. Patients on antiandrogens should be discontinued from flutamide, nilutamide or
cyproterone acetate for at least 4 weeks and bicalutamide for 6 weeks. If progression
is documented during or after this time interval, patients are eligible. Patients who
have not had response to deferred (secondary) therapy with antiandrogens do not have
to satisfy this waiting period prior to enrollment.

6. Patients must have a performance status of
7. Patients will not receive any concurrent biological, immunological, second-line
hormonal therapy or chemotherapy. Patients receiving replacement or therapeutic doses
of corticosteroid for non-malignant disease while disease progression was established
may continue on such therapy.

8. Patients must have recovered from prior chemotherapy, biological or immunological
therapy or radiation delivered within the last 28 days. Radioisotope therapy with
strontium delivered within the last 90 days or samarium within the last 60 days is
not permitted.

9. Patients must have a castrate serum testosterone level ( the last six weeks. For patients who are medically castrated, luteinizing hormone
releasing hormone analog must continue to maintain testicular suppression.

10. Patients must have adequate bone marrow function defined as an absolute peripheral
granulocyte count of >/= 1,500/mm^3 and platelet count of >/= 75,000/mm^3.

11. Patients must have adequate hepatic function defined with a bilirubin of upper limits of normal and AST/ALT
12. Patients must have adequate renal function defined as creatinine clearance >/= 40
cc/min (measured or calculated by Cockcroft and Gault formula).

13. Must be fully recovered from any previous surgery, in terms of wound healing.

14. Patients must sign an informed consent indicating that they are aware of the
investigational nature of this study, in keeping with the policies of the
institution.

15. All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®.

16. Men must agree to use a latex condom during sexual contact with a female of
childbearing potential (FCBP) even if they have had a successful vasectomy. A FCBP is
a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral
oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive
months (i.e., has had menses at any time in the preceding 24 consecutive months).

17. Patient must be able to take low molecular weight heparin (preferred) OR low-dose
enteric aspirin and warfarin for thromboembolic prophylaxis.

Exclusion Criteria:

1. Patients with severe or uncontrolled infection defined as symptomatic and/or
requiring intravenous antibiotics.

2. Patients with small cell or sarcomatoid variant of prostate cancer.

3. Patients with symptomatic congestive heart failure (CHF), pulmonary embolus, vascular
thrombosis, transient ischemic attack, cerebrovascular accident, unstable angina or
MI in the last 3 months or evidence of active myocardial ischemia by symptoms or
electrocardiogram (ECG).

4. Known severe hypersensitivity to taxanes.

5. Patients with central nervous system (CNS) metastasis or cord compression are
excluded except those patients that have had complete excision or radiotherapy and
remain asymptomatic for at least 2 months.

6. Oxygen-dependent lung disease or >/= grade 2 peripheral neuropathy.

7. Known intolerance of corticosteroid therapy that would preclude its use as
premedication for paclitaxel.

8. Uncontrolled severe hypertension or uncontrolled diabetes mellitus.

9. Active second malignancies. Non-threatening second malignancies such as superficial
low-grade transitional cell carcinoma of the bladder or Rai Stage 0 chronic
lymphocytic leukemia or stable small renal cell carcinomas may be exempt from such
stipulation at the discretion of the Principal Investigator.

10. Overt psychosis or mental disability or otherwise incompetent to give informed
consent. Patients who are unwilling or unable to comply with the RevAssist® program
or with a history of non-compliance with medical regimens or who are considered
potentially unreliable.

11. Patients with known HIV or active hepatitis A, B, or C infection.

12. Patients receiving any concurrent biological, immunological, second-line hormonal
therapy or chemotherapy. Patients receiving replacement or therapeutic doses of
corticosteroid for non-malignant disease while disease progression was established
may continue on such therapy.

13. Patients who have not recovered from prior chemotherapy, biological or immunological
therapy or radiation delivered within the last 28 days. Radioisotope therapy with
strontium delivered within the last 90 days or samarium within the last 60 days is
not permitted.

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 Time Frame:

Day 1, Days 8 and 15 of each cycle before Paclitaxel, then Day 1 of Cycle 3 and every 2 cycles thereafter

Safety Issue:

Yes

Principal Investigator

Lance Pagliaro, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2008-0606

NCT ID:

NCT00933426

Start Date:

August 2009

Completion Date:

Related Keywords:

  • Prostate Cancer
  • Castration-Resistant Prostate Cancer
  • CRPC
  • Prostate
  • Lenalidomide
  • Revlimid
  • CC-5103
  • Paclitaxel
  • Taxol
  • Taxanes
  • Prostatic Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030