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MelanomaPhase 1NCT01409174

IPI Biochemotherapy for Chemonaive Patients With Metastatic Melanoma

A Phase 1 study testing Ipilimumab, Temozolomide and Cisplatin in people with Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The goal of the Phase I part of this clinical research study is to find the highest tolerable dose of the drug Yervoy (ipilimumab) that can be given with the drugs Temodar (temozolomide), Intron-A (interferon alfa-2b), Proleukin (aldesleukin, IL-2), and Platinol (cisplatin) to patients with metastatic melanoma. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Melanoma
What is being tested?
Ipilimumab, Temozolomide and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited States
Study dates
Feb 2013to May 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with histologically documented diagnosis of advanced stage IV or unresectable stage III melanoma are eligible for Phase I and Phase II
  • They must have recurrent melanoma with measurable or evaluable sites of disease, 1.0 cm or larger, in order to assess the response to treatment by the immune-related response criteria
  • Phase I: Patients with prior therapy who do not have alternative treatment of higher priority will be eligible. Phase II: patients should not have been previously treated with cytotoxic drugs or drugs included in IPI-Biochemotherapy or regional therapy for metastatic malignant melanoma. Prior adjuvant interferon is permitted. Prior adjuvant Ipilimumab therapy is not permitted. Prior therapy with targeted therapy including but not limited to B-RAF, MEK inhibitors etc. is allowed. At least three weeks should have passed since the last dose of prior adjuvant interferon therapy and prior targeted therapies and patient has fully recovered from toxicities of drugs. 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.
  • Patients between 18 years of age and 65 years of age with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 will be eligible.
  • They should have normal blood counts with a (white blood cell (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.
  • 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), or active GI bleeding.
  • 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 72 hours prior to beginning treatment on this trial. Sexually active men must also use acceptable contraceptive methods for the duration of time on study.

Who cannot join

  • Patients with bone metastases only.
  • 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 are not eligible. Patients with treated central nervous system (CNS) metastases are not eligible for the neoadjuvant treatment cohort in Phase II. No major surgery or radiation therapy within 21 days before starting treatment.
  • 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.
  • 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 forced expiratory volume at one second (FEV1) to less than 75% of predicted normal values.
  • Patients with symptomatic effusions on account of pleural, pericardial or peritoneal metastases of melanoma.
  • Patients who are unable to return for follow-up visits as required by this study.
  • Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: IPI-Biochemotherapy for Chemonaive Patients With Metastatic Melanoma

The goal of the Phase I part of this clinical research study is to find the highest tolerable dose of the drug Yervoy (ipilimumab) that can be given with the drugs Temodar (temozolomide), Intron-A (interferon alfa-2b), Proleukin (aldesleukin, IL-2), and Platinol (cisplatin) to patients with metastatic melanoma. The safety of this combination will also be studied in Phase I. The goal of Phase II is to learn if this combination can help to control metastatic melanoma. Note: The study was closed following Phase I enrollment.

Ipilimumab, interferon alfa-2b, and aldesleukin are designed to block the activity of cells that decrease the immune system's ability to fight cancer.

Read more

Temozolomide is designed to stop cancer cells from making new DNA (the genetic material of cells). This may stop the cancer cells from dividing into new cells.

Cisplatin is designed to poison the cancer cells, which may cause them to die.

Read the detailed description

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 6 groups of 3 participants will be enrolled in the Phase I portion of the study, and up to 46 participants will be enrolled in Phase II.

*Study was halted early due to slow accrual in the Phase I portion without opening Phase II. *

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

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

All participants will receive the same dose level of cisplatin, temozolomide, interferon alfa-2b and IL-2.

If you develop intolerable side effects while on study, your dose of IL-2 may be lowered 1-2 times until the side effects get better.

Catheter:

If you are found to be eligible to take part in this study, you will have a central venous catheter (CVC) inserted, if you do not already have one. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.

Study Drug Administration:

The study drugs will be given in 3 stages: induction, consolidation, and maintenance.

Induction:

Induction will last 12 weeks. You will receive the study drugs in up to four 3-week cycles:

  • You will receive ipilimumab by vein over 90 minutes on Day 1 of each cycle.
  • You will take temozolomide by mouth 1 time a day on Days 2-5 of each cycle. You should take temozolomide on an empty stomach at least 2 hours before or after a meal. Do not open the capsule, mix it with food, or chew it.
  • You will receive cisplatin by vein over 1 hour on Days 2-4 of each cycle.
  • You will receive aldesleukin by vein as a continuous infusion on Days 2-5 of each cycle.
  • You will receive interferon alfa-2b as an injection under your skin on Days 2-6 of each cycle.

Consolidation:

Consolidation will last 12 weeks. You will receive the study drugs in three 4-week cycles.

  • You will receive ipilimumab by vein over 90 minutes on Day 1 of consolidation.
  • You will receive interferon alfa-2b as an injection under your skin on Days 1-5 of each cycle.
  • You will receive aldesleukin by vein as a continuous infusion on Days 2-5 of each cycle.

Maintenance:

Maintenance will last about 1½ years. You will receive ipilimumab by vein over 90 minutes on Day 1 of up to six 12-week cycles.

Other Drugs:

You will be given other drugs to help decrease 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:

Before each cycle (+/- 3 days):

  • You will be asked about any drugs you may be taking and any side effects you may have had.
  • Your performance status will be recorded.
  • Your vital signs will be measured.
  • If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.

Every week, blood (about 1 teaspoon) will be drawn for routine tests. Before each cycle, some of this blood will be used to check your liver and kidney function.

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

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

Anytime the doctor thinks it is needed, photos of the skin lesions 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 continue taking the study drugs for up to 2 years. 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 the study therapy, the following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your vital signs and weight.
  • Your performance status will be recorded.
  • You will be asked about any drugs you may be taking and any side effects you may have had.
  • 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.

Follow-Up:

Every 2 months for up to 3 years, you will be contacted by phone or during a clinic visit to see how you are doing.

This is an investigational study. Temozolomide, cisplatin, ipilimumab, interferon alfa-2b, and aldesleukin are FDA approved and commercially available to treat metastatic cancer. However, it is investigational to give temozolomide to patients with metastatic melanoma.

Up to 64 patients will take part in this study. All will be enrolled at MD Anderson.

Conditions
Melanoma
Being tested
Ipilimumab, Temozolomide, Cisplatin, Interferon Alfa-2b, Interleukin-2
Keywords
Melanoma, Metastatic, IPI-Biochemotherapy, Chemonaive, Advanced stage IV, Unresectable stage III melanoma, 1.0 cm or larger, Ipilimumab, Yervoy, BMS-734016, MDX010, Interferon Alpha-2b, Intron A, Temozolomide, Temodar, Cisplatin, Platinol-AQ, Platinol, CDDP, Interleukin-2
Medical subject headings
Melanoma, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpilimumabDrug

    Also called Yervoy, BMS-734016, MDX010

    Phase I Starting dose: 1 mg/kg by vein over 90 minutes on Day 1 of each 3 week cycle for Induction 12 weeks, then Day 1 of Cycle 1 for Consolidation 12 weeks and Day 1 of each 12 week cycle in Maintenance.

    Phase II dose: Maximum tolerated dose (MTD) from Phase I.

  • TemozolomideDrug

    Also called Temodar

    200 mg/m^2 by mouth 1 time a day on Days 2-5 of each Induction cycle (four 3 week cycles).

  • CisplatinDrug

    Also called Platinol-AQ, Platinol, CDDP

    25 mg/m^2 by vein over 1 hour on Days 2-4 of each Induction cycle (four 3 week cycles).

  • Interferon Alfa-2bDrug

    Also called Intron A

    5 million U/m2 subcutaneously on Days 2-6 of each 3 week Induction cycle (four 3 week cycles) and each 4 week Consolidation cycle (three 4 week cycles).

  • Interleukin-2Drug

    Also called IL-2, Aldesleukin, Proleukin

    9 million IU/m^2 by vein as a continuous infusion on Days 2-5 of each 3 week Induction cycle (four 3 week cycles) and each 4 week Consolidation cycle (three 4 week cycles).

Study groups in NCT01409174
Study groupRoleWhat they receive
Ipilimumab + ChemotherapyExperimentalIpilimumab starting 1 mg/kg by vein (IV) Day 1 each cycle; Temozolomide 200 mg/m^2 orally Days 2-5 of Induction; Cisplatin 25 mg/m^2 IV for Days 2-4 of Induction; Interferon alfa-2b 5 million U/m2 subcutaneously on Days 1-5 of each cycle Induction + Consolidation; and Interleukin-2 9 million IU/m^2 IV as a continuous infusion on Days 2-5 of Induction + Consolidation.
Receives: Drug: Ipilimumab; Drug: Temozolomide; Drug: Cisplatin; Drug: Interferon Alfa-2b; Drug: Interleukin-2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Tumor Response by Participant using immune-related response criteria (irRC)

    Tumor assessments using irRC modified World Health Organizations (WHO) criteria: Immune-Related Complete Response (irCR): Complete disappearance of all tumor lesions. Immune-Related Partial Response (irPR): decrease of 50% or greater. Immune-Related Progressive Disease (irPD): At least 25% increase in sum of products of all index lesions over baseline sum of products of diameters (SPD) calculated for index lesions. Assessment include photographic measurement of skin lesions, computed tomography scans and/or magnetic resonance imaging tumor assessments until documented tumor progression.

    Measured: End of 2 cycles, 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2011 (estimated)
  2. Study startFeb 2013
  3. Primary completionMay 2016
  4. Study completionMay 2016

Why it stopped: Slow accrual, closed in Phase I.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01409174
Sponsor's protocol ID
2011-0073
Other IDs
NCI-2011-02768
Status last verified
May 2017
First submitted
2 Aug 2011
Last updated
31 May 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ipilimumab, Temozolomide and Cisplatin in people with Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Slow accrual, closed in Phase I.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tumor Response by Participant using immune-related response criteria (irRC) (time frame: End of 2 cycles, 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01409174.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2017.

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