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Systemic Therapy of Metastatic Melanoma With Multidrug Regimen Including Interferon, Interleukin-2 and BRAF Inhibitor

Phase 1/Phase 2
18 Years
Not Enrolling

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Trial Information

Systemic Therapy of Metastatic Melanoma With Multidrug Regimen Including Interferon, Interleukin-2 and BRAF Inhibitor

Study Groups:

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 join this study. Up to 4 groups of 6 participants will be enrolled
in the Phase I portion of the study and up to 53 participants will be enrolled in Phase II.

If you are enrolled in the Phase I portion, the dose of vemurafenib and aldesleukin you
receive will depend on when you joined this study. The first group of participants will
receive the lowest dose levels of vemurafenib and aldesleukin. Each new group will receive a
higher dose of vemurafenib or aldesleukin than the group before it, if no intolerable side
effects were seen. This will continue until the highest tolerable doses of vemurafenib and
aldesleukin are found.

If you are enrolled in the Phase II portion, you will receive vemurafenib and aldesleukin at
the highest doses that were tolerated in the Phase I portion.

All participants will receive the same dose level interferon alfa-2b.

Study Drug Administration:

Each study cycle is 21 days.

You will take vemurafenib by mouth twice a day (1 time in the morning and 1 time in the
evening) every day of each study cycle. Vemurafenib can be taken with or without food. If
you miss a scheduled dose of vemurafenib, do not try to "make up" the dose by taking 2 doses
at the next scheduled dosing time. Continue taking the study drug as scheduled

You will receive aldesleukin by vein over 72 hours on Days 2-5 of each study cycle.

You will receive interferon alfa-2b as an injection under your skin on Days 1-5 of each
study cycle.

Supportive Drugs:

You will be given other drugs to help lower the risk of side effects. The study staff will
tell you about these drugs, how they will be given, and the possible risks.

Study Visits:

The following tests and procedures will be performed:

On Day 1 (+/- 3 days) of each cycle:

- Your performance status will be recorded.

- Your vital signs will be measured.

- You will be asked about any drugs you may be taking and any side effects you may have

- If you are able to become pregnant, you will have a blood (about 1 teaspoon) pregnancy

Your skin will be checked for non-melanoma skin cancers on Day 1 of Cycle 1 (+/-3 days) and
then every 3 cycles.

Blood (about 1 teaspoon) will be drawn for routine tests on Days 1, 8, and 15 of each cycle.
On Day 1 of each cycle, some of this blood will be used to check your liver and kidney

At the end of each cycle (Day 21), you will have a physical exam, including measurement of
your weight. Any tumor that can be felt with the hands will be measured with measuring tape
during the physical exam to see if it has changed size.

On Day 21 (+/- 7 days) of every 2 cycles, you will have a chest x-ray and a CT or MRI scan
to check the status of the disease.

Anytime the doctor thinks it is needed, photos of any skin lesions you have will be taken.
Your private areas will be covered (as much as possible), and a picture of your face will
not be taken unless there are lesions on your face.

Length of Study:

You may take the study drug combination for as long as the doctor thinks you are
benefitting. You will no longer be able to take the study drugs if the disease gets worse,
if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the end-of-treatment
visit and follow-up.

End-of-Treatment Visit:

Within 14 days after you stop taking the study drug combination, the following tests and
procedures will be performed:

- Your performance status will be recorded.

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

- You will be asked about any drugs you may be taking and any side effects you may have

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

- If the doctor thinks it is needed, you will have a CT or MRI scan.


Every 3 months for up to 3 years, you will be contacted by phone or during a clinic visit to
see how you are doing. The phone call should last about 5 minutes.

This is an investigational study. Vemurafenib, interferon alfa-2b, and Aldesleukin are FDA
approved and commercially available to treat metastatic cancer. Giving these drugs in
combination is investigational.

Up to 71 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients with histologically documented diagnosis of advanced stage IV or
unresectable stage III skin or mucosal melanoma are eligible if they have BRAF
mutation affecting the V600 site, as determined by a CLIA-certified assay. Mutation
testing of archival tumor tissue is acceptable, or it may be performed on new biopsy.
If a new biopsy is performed for testing, biopsy of a metastasis is preferred to
biopsy of a primary tumor.

2. Patients must have at least one bidimensionally measurable lesion. If this is a
cutaneous lesion it must be at least 10 mm by caliper measure. If it is a visceral or
nodal or soft tissue lesion, it must be clearly measurable > 20 mm with conventional
techniques or > 10 mm with spiral CT scan. Bone lesions are not considered

3. Phase I: Patients with prior therapy who do not have alternative treatment of higher
priority will be eligible. Phase II: the patient may have been treated with cytotoxic
drugs or targeted therapies for metastatic disease but not with IL-2, interferon and
BRAF inhibitor drugs. Adjuvant interferon will be permitted. Prior radiation therapy
for metastatic melanoma is permitted provided the patient has unirradiated metastatic
sites for response evaluation and has fully recovered from its toxicity.

4. Patients between 18 years of age and 65 years of age with an ECOG performance status
of 0, 1 or 2 will be eligible.

5. They should have normal blood counts with a WBC count of more than or equal to
3000/mm^3 an absolute neutrophil count of more than or equal to 1500/mm^3 and a
platelet count of more than 100,000/mm^3 and have no impairment of renal function
(serum creatinine less than 1.1 mg/dl for females and less than 1.4 mg/dl for males),
hepatic function (serum bilirubin level of less than 1.2 mg/dl) and no evidence of
significant cardiac or pulmonary dysfunction.

6. They should have no significant intercurrent illness such as an active infection
associated with fever lasting more than 24 hours requiring antibiotics, uncontrolled
psychiatric illness, hypercalcemia (calcium greater than 11 mg), active GI bleeding,
myocardial disease with QTC interval > 480 on baseline ECG or history of rheumatoid

7. Females of child-bearing potential (non-childbearing is defined as greater than one
year post-menopausal or surgically sterilized) must use acceptable contraceptive
methods( abstinence, intrauterine device, oral contraceptive or double barrier
devices) and must have a negative serum or urine pregnancy test within 14 days prior
to beginning treatment on this trial. Sexually active men must also use acceptable
contraceptive methods for the duration of time on study.

Exclusion Criteria:

1. Patients with uveal melanoma.

2. Patients with bone metastases only.

3. Patients with brain metastases unless all of their metastatic brain lesions have been
resected or treated with stereotactic radiotherapy with gamma rays and they are off
corticosteroids. Patient should not have significant brain edema. Patients with
spinal cord compression and leptomeningeal disease. No major surgery or radiation
therapy within 21 days before starting treatment.

4. Patients with significant cardiac illness such as symptomatic coronary artery disease
or previous history of myocardial infarction, impaired left ventricle function
(Ejection Fraction less than 50%) on account of any organic disease such as
hypertension or valvular heart disease or serious cardiac arrhythmia requiring
therapy. Patients will be evaluated by the investigator or his designee.

5. Patients with significant impairment of pulmonary function on account of chronic
bronchitis or chronic obstructive pulmonary disease (COPD) which has resulted in
impairment of vital capacity of FEV1 to less than 65 % of predicted normal values.

6. Patients with symptomatic effusions on account of pleural, pericardial or peritoneal
metastases of melanoma.

7. Patients who are unable to return for follow-up visits as required by this study.

8. Patients with a history of second malignant tumor, other than the common skin cancers
- basal and squamous carcinomas, within the past 3 years and uncertainty about the
histological nature of the metastatic lesions. Cases with other types of malignancies
should be reviewed and decided by the PI of the study.

Type of Study:


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:

Maximum tolerated dose (MTD) defined as highest dose studied in which incidence of dose limiting toxicity (DLT) was less than 33%. DLT defined as any grade 3 or 4 non-hematological toxicity excluding manageable N/V, diarrhea and fatigue and manageable/replaceable grade 3 or 4 electrolyte abnormalities, and appearance of new squamous cell skin cancers. Toxicity that may result in delaying next course for more than 3 weeks. Any grade 4 neutropenia more than 7 days duration or Grade 4 thrombocytopenia lasting more than 7 days.

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Agop Y. Bedikian, MD,BS

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

March 2013

Completion Date:

Related Keywords:

  • Melanoma
  • Melanoma
  • Metastatic melanoma
  • Advanced melanoma
  • Vemurafenib
  • PLX4032
  • RO5185426
  • IL-2
  • Interleukin-2
  • Aldesleukin
  • Proleukin
  • Interferon Alfa-2b
  • Intron A
  • Melanoma