Phase II Study of Abraxane Plus Ipilimumab in Patients With Metastatic Melanoma

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT01827111
Collaborator
Celgene (Industry)
21
Enrollment
1
Location
1
Arm
88.9
Actual Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if the combination of ipilimumab and ABI-007 (abraxane) can help to control metastatic melanoma. The safety of this drug combination will also be studied.

Ipilimumab is designed to increase the immune system's ability to fight cancer.

Abraxane 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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive ABI-007 by vein over about 30 minutes on Days 1, 8, and 15 of each 28-day cycle. During the first 3 months that you receive abraxane, you will also receive ipilimumab. You will receive ipilimumab by vein over about 90 minutes. You will receive it 4 times, each time about 3 weeks apart.

You will be given standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks.

Study Tests:

Every week, blood (about 1 teaspoon) will be drawn for routine tests.

Before each cycle of abraxane:
  • Your performance status will be recorded.

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

  • Blood (about 1 teaspoon) will be drawn for routine tests.

  • Blood (about 1 teaspoon) will be drawn for tests of the immune system (first 3 cycles only).

  • You will be asked about any other drugs you may be taking and about any side effects you may be having.

  • If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.

Every 8 weeks (+/- 7 days), you will have a chest x-ray and CT scans or MRI scans performed to check the status of the disease.

Length of Study:

You may receive ipilimumab for up to 3 months. You may continue taking abraxane for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.

If you stop receiving the study drugs for any reason, you will have an End-of-Treatment Visit.

End-of-Treatment Visit:

Within 14 days after you stop study treatment, you will come into the clinic for the

End-of-Treatment Visit. At this visit, the following tests will be performed:
  • You will have a physical exam, including measurement of your vital signs and weight.

  • You will be asked about any other drugs you may be taking and any side effects you may be having.

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

  • If the study doctor thinks it is in your best interest, you will have a CT scan or MRI scan to check for side effects.

Every 2 months for 6 months, then every 3 months for up to 2 years, you will also be contacted by telephone or during a routine clinic visit to see how you are doing. If you are called, each call should last about 5 minutes.

This is an investigational study. Ipilimumab is FDA approved and commercially available for the treatment of metastatic melanoma. abraxane is FDA approved and commercially available for the treatment of metastatic breast cancer. It is investigational to use abraxane, either alone or in combination with ipilimumab, for the treatment of metastatic melanoma.

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

Study Design

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study of Abraxane Plus Ipilimumab in Patients With Metastatic Melanoma
Actual Study Start Date :
Apr 25, 2013
Actual Primary Completion Date :
Sep 21, 2020
Actual Study Completion Date :
Sep 21, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: ABI-007 + Ipilimumab

Starting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. Ipilimumab 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses. Every 2 months for 6 months, then every 3 months for up to 2 years, participant contacted by telephone. Each call should last about 5 minutes.

Drug: ABI-007
Starting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. The cycle length for ABI-007 is 28 days.
Other Names:
  • Nab-paclitaxel
  • Paclitaxel
  • Abraxane
  • Drug: Ipilimumab
    3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses.
    Other Names:
  • Yervoy
  • BMS-734016
  • MDX010
  • Behavioral: Phone Call
    Every 2 months for 6 months, then every 3 months for up to 2 years, participant contacted by telephone. Each call should last about 5 minutes.

    Outcome Measures

    Primary Outcome Measures

    1. Median Overall Survival Response to Abraxane Plus Ipilimumab Therapy [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 50 months]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.1) was used. Complete Response (CR)= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, no new lesions; Partial Response (PR)= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    2. Median Progression Free Survival [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 50 months]

      Progression-free survival (PFS) is the time from random assignment in a clinical trial to disease progression or death from any cause.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Patients with histologically documented diagnosis of advanced stage IV or unresectable stage III mucosal or cutaneous melanoma are eligible.

    2. 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 (irRC).

    3. Patients should not have been previously treated with cytotoxic drugs and immunotherapeutic agents for unresectable Stage III or Stage IV disease. Prior Ipilimumab in metastatic setting is not allowed. Prior therapy may include one line of targeted therapy for metastatic disease ie BRAF or MEK inhibitor. At least 3 weeks should have passed since the last dose of prior adjuvant interferon therapy and prior targeted therapies, and all previous therapy related toxicities should have resolved before starting study treatment. Prior adjuvant interferon is permitted. Prior cytotoxic therapy in adjuvant or metastatic setting is not allowed. Prior Ipilimumab in adjuvant setting is not allowed. Prior adjuvant therapy with targeted therapy including but not limited to B-RAF, MEK inhibitors etc. is allowed. Prior palliative 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 12 years of age and 70 years of age with an ECOG performance status of 0 or 1 will be eligible

    5. They should have normal blood counts with a white blood cell count of more than or equal to 3000/mm3 an absolute neutrophil count of more than or equal to 1500/mm3 and a platelet count of more than 100,000/mm^3, Hemoglobin > 9.0 g/dL 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 1.5 mg/dl, AST and ALT </= 2.5X ULN unless presence of hepatic metastasis in which case AST and ALT </= 5X ULN are acceptable. Alk Phos </= 2.5X ULN ) 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), 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 and signed informed consent .

    Exclusion Criteria:
    1. Patients with metastatic uveal melanoma

    2. Patients with bone metastases only.

    3. Patients with symptomatic brain or spinal cord metastases or requiring steroid therapy and patients with leptomeningeal disease. Patients with treated and stable CNS metastasis for 3 months or more, off steroids are eligible for the study. 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 with significant history of cardiac disease will be evaluated by the investigator or his designee.

    5. Patients with significant impairment of pulmonary function on account of chronic bronchitis, emphysema or chronic obstructive pulmonary disease (COPD) which has resulted in impairment of vital capacity of FEV1 to less than 75% 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. 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.
    1. Patients with ≥ grade 2 sensory neuropathy at baseline.

    2. Patients who have had major surgery or radiation therapy within 21 days of starting treatment.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Texas MD Anderson Cancer CenterHoustonTexasUnited States77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center
    • Celgene

    Investigators

    • Principal Investigator: Adi Diab, MD, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01827111
    Other Study ID Numbers:
    • 2011-1157
    • NCI-2014-01238
    First Posted:
    Apr 9, 2013
    Last Update Posted:
    Feb 8, 2022
    Last Verified:
    Jan 1, 2022

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail21 participants signed the consent, 2 participants did not received treatment (1) withdrew prior treatment and (1) not eligible due to angiosarcoma (no melanoma).
    Arm/Group TitleABI-007 + Ipilimumab
    Arm/Group DescriptionStarting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. Ipilimumab 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses. Every 2 months for 6 months, then every 3 months for up to 2 years, participant contacted by telephone. Each call should last about 5 minutes. ABI-007: Starting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. The cycle length for ABI-007 is 28 days. Ipilimumab: 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses. Phone Call: Every 2 months for 6 months, then every 3 months for up to 2 years, participant contacted by telephone. Each call should last about 5 minutes.
    Period Title: Overall Study
    STARTED19
    COMPLETED18
    NOT COMPLETED1

    Baseline Characteristics

    Arm/Group TitleABI-007 + Ipilimumab
    Arm/Group DescriptionStarting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. Ipilimumab 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses. Every 2 months for 6 months, then every 3 months for up to 2 years, participant contacted by telephone. Each call should last about 5 minutes. ABI-007: Starting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. The cycle length for ABI-007 is 28 days. Ipilimumab: 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses. Phone Call: Every 2 months for 6 months, then every 3 months for up to 2 years, participant contacted by telephone. Each call should last about 5 minutes.
    Overall Participants18
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    13
    72.2%
    >=65 years
    5
    27.8%
    Sex: Female, Male (Count of Participants)
    Female
    6
    33.3%
    Male
    12
    66.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    18
    100%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    18
    100%

    Outcome Measures

    1. Primary Outcome
    TitleMedian Overall Survival Response to Abraxane Plus Ipilimumab Therapy
    DescriptionPer Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.1) was used. Complete Response (CR)= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, no new lesions; Partial Response (PR)= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    Time FrameFrom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 50 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleABI-007 + Ipilimumab
    Arm/Group DescriptionStarting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. Ipilimumab 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses.
    Measure Participants18
    Median (Full Range) [months]
    24.9
    2. Primary Outcome
    TitleMedian Progression Free Survival
    DescriptionProgression-free survival (PFS) is the time from random assignment in a clinical trial to disease progression or death from any cause.
    Time FrameFrom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 50 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleABI-007 + Ipilimumab
    Arm/Group DescriptionStarting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. Ipilimumab 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses.
    Measure Participants18
    Median (95% Confidence Interval) [months]
    10

    Adverse Events

    Time Frameup to 50 months
    Adverse Event Reporting Description
    Arm/Group TitleABI-007 + Ipilimumab
    Arm/Group DescriptionStarting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. Ipilimumab 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses.
    All Cause Mortality
    ABI-007 + Ipilimumab
    Affected / at Risk (%)# Events
    Total0/18 (0%)
    Serious Adverse Events
    ABI-007 + Ipilimumab
    Affected / at Risk (%)# Events
    Total2/18 (11.1%)
    Cardiac disorders
    Hypotension1/18 (5.6%)
    Endocrine disorders
    Hypophysitis2/18 (11.1%)
    Eye disorders
    Macular Cystoid1/18 (5.6%)
    Gastrointestinal disorders
    Colitis2/18 (11.1%)
    Nausea1/18 (5.6%)
    Vomiting1/18 (5.6%)
    General disorders
    Fever2/18 (11.1%)
    Investigations
    Wound Infection1/18 (5.6%)
    Metabolism and nutrition disorders
    Hyponatremia1/18 (5.6%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea1/18 (5.6%)
    Lung Infection1/18 (5.6%)
    Other (Not Including Serious) Adverse Events
    ABI-007 + Ipilimumab
    Affected / at Risk (%)# Events
    Total18/18 (100%)
    Blood and lymphatic system disorders
    Anemia8/18 (44.4%)
    Thrombocytopenia2/18 (11.1%)
    Cardiac disorders
    Hypertension5/18 (27.8%)
    Endocrine disorders
    Hypothyroidism3/18 (16.7%)
    Hypophysitis2/18 (11.1%)
    Gastrointestinal disorders
    Diarrhea14/18 (77.8%)
    Nausea11/18 (61.1%)
    Vomiting8/18 (44.4%)
    Constipation7/18 (38.9%)
    Mucositis3/18 (16.7%)
    General disorders
    Fatigue16/18 (88.9%)
    Pain12/18 (66.7%)
    Chills4/18 (22.2%)
    Fever3/18 (16.7%)
    Investigations
    Transaminitis11/18 (61.1%)
    Elevated Bilirubin2/18 (11.1%)
    Elevated Creatinine2/18 (11.1%)
    Metabolism and nutrition disorders
    Anorexia11/18 (61.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia14/18 (77.8%)
    Myalgia13/18 (72.2%)
    Nervous system disorders
    Neuropathy15/18 (83.3%)
    Headache7/18 (38.9%)
    Skin and subcutaneous tissue disorders
    Alopecia18/18 (100%)
    Rash16/18 (88.9%)
    Pruritis13/18 (72.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleAdi Diab, MD-Associate Professor, Melanoma Medical Oncology
    OrganizationUT MD Anderson Cancer Center
    Phone(713) 745-7336
    Emailadiab@mdanderson.org
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01827111
    Other Study ID Numbers:
    • 2011-1157
    • NCI-2014-01238
    First Posted:
    Apr 9, 2013
    Last Update Posted:
    Feb 8, 2022
    Last Verified:
    Jan 1, 2022