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A Phase II Trial of High Dose Interleukin-2 (HDIL-2) With Recombinant MAGE-A3 Protein Combined With Adjuvant System AS15 (recMAGE-A3 + AS15) in Patients With Unresectable or Metastatic Melanoma


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Melanoma

Thank you

Trial Information

A Phase II Trial of High Dose Interleukin-2 (HDIL-2) With Recombinant MAGE-A3 Protein Combined With Adjuvant System AS15 (recMAGE-A3 + AS15) in Patients With Unresectable or Metastatic Melanoma


The Study Drugs:

HDIL-2 is similar to a hormone naturally found in the body that boosts the immune system by
helping "natural killer" (NK) cells live longer and work better. NK cells are a type of
white blood cell that kill other cells, and they may kill cancer cells.

ASCI is a immunotherapy designed to teach your immune system to fight cancer in the same way
that you are given vaccines to prevent disease by teaching your immune system to fight an
infection caused by germs. Because the cancer is made by your own body, the immune system
does not recognize the cancer cells as being harmful. Your immune system needs to be
"trained" to recognize the cancer cells. This is done by injecting a protein (the MAGE-A3
protein) that is found in the tumor and training your body to recognize it and to destroy
the cells that have this protein. This may increase the effectiveness of IL-2 by slowing
the growth of the cancer cells, which may cause them to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will begin the study drugs
within 14 days of signing the second consent form. To receive the study drugs, you will be
admitted to the hospital, either in the intensive care unit (ICU) or a specifically
designated nursing unit where study drugs can be administered, on Day 2 of each cycle and
may remain in the hospital for up to 7 days each cycle.

You may receive a total of 24 ASCI doses either in combination with HDIL-2 or alone. You
may receive the study drugs in combination for up to 30 weeks. After that, you may receive
the ASCI study medication alone for up to 176 more weeks.

Cycle 1 is 14 days (Weeks 1 and 2):

- On Day 1 of Cycle 1, you will receive the ASCI study medication as an injection. Each
injection will be given in the muscle of your upper arm or in your thigh. You will be
watched in the clinic for at least 30 minutes after each injection.

- On Day 2 (+/- 2 business days), you will receive HDIL-2 through a catheter (a small
plastic tube that is put into your vein under your collar bone or in your arm) over 15
minutes. HDIL-2 treatment will be delayed in cycles 2, 3, 4, 5, 6, 7, or 8 until all
HDIL-2 related side effects either go away or the study doctor thinks they are under
control.

Cycle 2 is 42 days (Weeks 3-8):

- On Day 1 of Weeks 3, 5, and 7 (+/- 2 business days) , you will receive the ASCI study
medication as an injection.

- On Day 2 of Week 3 (+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 3 is 14 days (Weeks 9 and 10):

- On Day 1 of Week 9 (+/- 2 business days), you will receive the ASCI study medication as
an injection.

- On Day 2 of Week 9 (+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 4 is 49 days (Weeks 11-17):

- On Day 1 of Weeks 11 and 15 (+/- 2 business days), you will receive the ASCI study
medication as an injection.

- On Day 2 of Week 11 (+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 5 is 21 days (Weeks 18-20):

- On Day 1 of Week 18 (+/- 2 business days), you will receive the ASCI study medication
an injection.

- On Day 2 of Week 18 (+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 6 is 42 days (Weeks 21-26):

- On Day 1 of Weeks 18, 21, and 24 (+/- 2 business days), you will receive the ASCI study
medication as an injection.

- On Day 2 of Weeks 18 and 21 (+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 7 is 21 days (Weeks 27-29):

- On Day 1 of Week 27 (+/- 2 business days), you will receive the ASCI study medication
as an injection.

- On Day 2 of Week 27(+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 8 is 28 days (Weeks 30-33):

- On Day 1 of Week 30 (+/- 2 business days), you will receive the ASCI study medication
as an injection.

- On Day 2 of Week 30 (+/- 2 business days), you will receive HDIL-2 by vein.

On Day 1 of Weeks 34, 40, 46, 52, 64, 76, 88, and 100 (+/- 2 business days), you will
receive the ASCI study medication as an injection.

Study Visits:

On Day 1 of Weeks 1, 3, 5, 7, 9, 11, 15, 18, 21, 24, 27, and 30 (+/- 2 business days):

- You will have a physical exam, including measurement of your weight and vital signs.
Blood (about 2 tablespoons) will be drawn for routine tests.

- You will be asked about any side effects you may be having and drugs you are taking.

On Day 2 of Weeks 1, 3, 5, 7, 9, 11, 18, 21, 27, and 30 (+/- 2 business days):

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

- You will be asked about any side effects you may be having and drugs you are taking.

During Weeks 8, 17, 26, and 33, 34, 40, 46 and 52 and every 12 weeks thereafter (+/- 7
days): (+/- 7 days):

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

- You will also have an MRI scan or CT scan of the brain to check the status of the
disease.

- You will have photographs of your lesions taken if indicated by your doctor.

On Day 1 of Weeks 34, 40, 46, 52, 64, 76, 88, and 100 (+/- 2 business days):

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

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

- You will be asked about any side effects you may be having and drugs you are taking.

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

- You will also have an MRI scan or CT scan of the brain to check the status of the
disease.

- You will have photographs of your lesions taken if indicated by your doctor.

Additional Blood Draws:

Additional blood (about 4 tablespoons each time) will be drawn for laboratory tests to look
at how the study drug combination may affect the immune system. These blood draws will be
collected on Day 1 of cycle 1 and again during cycle 1 48 hours after the last dose of
IL-2. Additional blood draws (about 4 tablespoons each time) will also Part of the blood
drawn for these tests will be sent to GSK Biologicals (or a contracted laboratory) for
testing.

Length of Study:

You may continue to receive the study drug combination for up to 8 cycles (33 weeks) and
ASCI alone for up to 76 more weeks (+/- 2 business days). If you continue beyond
completing 8 cycles of HDIL-2, you will receive the ASCI on Day 1 (+/- 2 business days)
every 6 weeks for 4 doses (weeks 34, 50, 46, and 52), then on Day 1 (+/- 2 business days)
every 12 weeks (weeks 64, 76, 98, and 110) for 4 doses, then on Day 1 (+/- 2 business days)
every 24 weeks (weeks 134, 158, 182, and 206) for 4 doses.

You will be taken off the study therapy early if the disease gets worse, you experience
intolerable side effects, or the study doctor thinks it is in your best interest. If you are
removed from the study because of intolerable side effects, you will be followed weekly by
either a phone call or clinic visit until the side effect is tolerable.

End-of-Dosing Visit:

After receiving the last dose of study drug combination, you will have an end-of-dosing
visit:

- Your medical history will be reviewed and you will be asked about any side effects you
may be having and drugs you are taking.

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

- Blood (about 3 tablespoons) will be drawn for routine tests and ANA testing.

Follow-Up Visits:

You will have follow-up visits after your last dose of study drug, if the disease does not
get any worse. Starting after the last dose of study drug, you will have 1 visit every 3
months for the 1st year, every 4 months for the 2nd year, every 6 months for the 3rd and 4th
year, then once a year for up to 10 years (+/- 2 business days). At these visits, the
following will be performed:

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

- If the study doctor thinks it is needed, blood (about 2 tablespoons) will be drawn for
routine tests.

- If the study doctor thinks it is needed, you will have a chest x-ray, CT scan of your
chest, abdomen, and pelvis, and/or MRI scan or CT scan of the brain to check the status
of the disease.

If the disease begins to get worse, information about the status of your health will be
collected every 2 months. If you are not able to come into the clinic to complete this
visit, you will be asked for this information over the phone. The phone call should last
about 10-15 minutes each time.

This is an investigational study. IL-2 is commercially available and FDA approved for the
treatment of metastatic melanoma. HDIL-2 is a higher dose than the standard approved dose
of IL-2. The ASCI study medication is not FDA approved or commercially available. It is
currently being used for research purposes only.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Written informed consent has been obtained from the patient before the performance of
any protocol-specific procedure.

2. Male or female patient with histologically proven, measurable unresectable or
metastatic cutaneous melanoma

3. Patient is >/= 18 years of age.

4. Patients must have at least one biopsiable cutaneous, subcutaneous, lymph node
lesion, lung or liver lesion and willing to undergo a punch or a CT or US guided
biopsy of this lesion. Cutaneous lesions must measure >/= 4mm and lymph nodes,
subcutaneous, lung or liver lesions must measure >/= 1cm.

5. ANA (antinuclear antibody) titer < 1:80

6. The patient's tumor shows expression of MAGE-A3 gene.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

8. White Blood Count (WBC) >/= 3000/mm^3 and Hemoglobin >/= 9 g/dl

9. Platelet count >/= 100,000/mm^3.

10. Normal aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or
SGPT) except for patients with liver metastases, in which serum ALT and AST upper limit of normal (ULN) will be permitted.

11. Creatinine
12. Normal total bilirubin except for patients with liver metastases, in which total
bilirubin a total bilirubin less that 3.0 mg/dL).

13. Lactate dehydrogenase (LDH or LD)
14. Stress cardiac test (stress thallium, stress MUGA (Multi Gated Acquisition Scan),
dobutamine echocardiogram or other stress test that will rule out cardiac ischemia)
with estimated ejection fraction >50% within 6 months of signing consent form

15. Pulmonary function tests showing FEV1 > 65% or FVC > 65% of predicted within 6 months
of signing consent form

16. Women of childbearing potential (WOCBP) must be using an adequate method of
contraception prior to treatment, throughout the study, and for up to 8 weeks after
the last dose of investigational product, in such a manner that the risk of pregnancy
is minimized. In general, the decision for appropriate methods to prevent pregnancy
should be determined by discussions between the investigator and the study subject.
WOCBP include any female who has experienced menarche and who has not undergone
successful surgical sterilization (hysterectomy, bilateral tubal ligation, or
bilateral oophorectomy) or is not post-menopausal. Post-menopause is defined as:
Amenorrhea for 12 consecutive months without another cause, or For women with
irregular menstrual periods and taking hormone replacement therapy (HRT), a
documented serum follicle stimulating hormone (FSH) level 35 mIU/mL.

17. (Continued #16) Women who are using oral contraceptives, other hormonal
contraceptives (vaginal products, skin patches, or implanted or injectable products),
or mechanical products such as an intrauterine device or barrier methods (diaphragm,
condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where
their partner is sterile (eg, vasectomy) should be considered to be of childbearing
potential. WOCBP must have a negative serum or urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of HCG) within 14 days before the start of
treatment.

18. Men must also agree to use an adequate method of contraception.

Exclusion Criteria:

1. The patient has at any time received systemic chemotherapy, immunotherapy or targeted
therapy (except for isolated limb perfusion, interferon, or radiation in the adjuvant
setting, as long as this was performed at least 4 weeks before first study treatment
administration).

2. Brain metastasis or history of brain metastasis.

3. Any types of melanoma other than cutaneous, i.e. ocular or mucosal .

4. The patient received any cancer immunotherapeutic containing a MAGE-A3 antigen.

5. Patients with a history of second malignancies are eligible provided that they have
been free of recurrence from secondary malignancy for at least 3 years, does not
include squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ.

6. The patient has a history of an autoimmune disease such as, but not limited to,
multiple sclerosis, lupus, rheumatoid arthritis, and inflammatory bowel disease or an
antinuclear antibody (ANA) titer > 1:80.

7. The patient has a history of allergic disease or reactions likely to be exacerbated
by any component of the study investigational compound.

8. The patient has a family history of congenital or hereditary immunodeficiency.

9. Known to be positive for viral hepatitis B or C (HBsAg or Anti HCV) or HIV (HIV
antibodies).

10. Systemic steroid therapy, steroid-containing compounds or any other immunosuppressive
agents or to be used for more than 7 consecutive days (at a dose of prednisone or
equivalent of >/= 0.125 mg/kg/day).

11. The patient has psychiatric or addictive disorders that may compromise his/her
ability to give informed consent, or to comply with the trial procedures. Each
patient will be evaluated by the principal investigator or his designee.

12. The patient has concurrent severe medical problems, unrelated to the malignancy, that
would significantly limit full compliance with the study or expose the patient to
unacceptable risk. Each patient will be evaluated by the principal investigator or
his designee.

13. Initiation of another anti-cancer therapy.

14. For female patients: the patient is pregnant or lactating.

15. WOCBP who are unwilling or unable to use an acceptable contraceptive method to avoid
pregnancy.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Objective Response Rate

Outcome Description:

Objective response is either a complete response or a partial response measured at week 8. Tumor response defined by Response Evaluation Criteria in Solid Tumors (RECIST) solid tumor response criteria by MR or CT.

Outcome Time Frame:

8 weeks

Safety Issue:

No

Principal Investigator

Wen-Jen Hwu, MD,PHD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2010-0113

NCT ID:

NCT01266603

Start Date:

February 2012

Completion Date:

Related Keywords:

  • Melanoma
  • Metastatic Melanoma
  • Unresectable Melanoma
  • HDIL-2
  • Interleukin-2
  • IL-2
  • Aldesleukin
  • Proleukin
  • recMAGE-A3 + AS15
  • ASCI
  • recMAGE-A3
  • Recombinant MAGE-A3 protein
  • recMAGE-A3 + AS15 ASCI
  • MAGE-A3
  • MAGE-A3 ASCI
  • Melanoma

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030