Clinical Trials /

Ipilimumab and Dabrafenib in the 1st Line Tx of Unresectable Stage III/IV Melanoma

NCT02200562

Description:

Phase I/II study of ipilimumab concurrent ipilimumab and dabrafenib as first line treatment in Stage III or IV melanoma. Assessing safety of Ipilimumab and dabrafenib in combination. Also, assessing disease control rates.

Related Conditions:
  • Melanoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Ipilimumab and Dabrafenib</span> in the 1st Line Tx of Unresectable Stage III/IV <span class="go-doc-concept go-doc-disease">Melanoma</span>

Title

  • Brief Title: Ipilimumab and Dabrafenib in the 1st Line Tx of Unresectable Stage III/IV Melanoma
  • Official Title: A Phase I/II Study of Concurrent Ipilimumab and Dabrafenib in Unresectable Stage III or Stage IV Melanoma
  • Clinical Trial IDs

    NCT ID: NCT02200562

    ORG ID: HCI68132

    Trial Conditions

    Stage III or IV Melanoma

    Trial Interventions

    Drug Synonyms Arms
    ipilimumab and dabrafenib Ipilimumab and Dabrafenib

    Trial Purpose

    Phase I/II study of ipilimumab concurrent ipilimumab and dabrafenib as first line treatment
    in Stage III or IV melanoma.

    Assessing safety of Ipilimumab and dabrafenib in combination. Also, assessing disease
    control rates.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Ipilimumab and Dabrafenib Experimental ipilimumab and dabrafenib

    Eligibility Criteria

    Inclusion Criteria:

    - For Phase I: Locally advanced or metastatic BRAF V600E/K/R positive melanoma that is
    either treatment-nave or treatment-experienced. For the latter, progression, or
    stable as best response, or intolerance to the last treatment is required. Previous
    treatments can be local or systemic therapies. There are no limits to the number of
    prior therapies. For all patients, disease does not have to be measurable but must be
    evaluable, which is defined as one or more lesions which are known to be present, but
    which cannot be measured. eg: Bony lesions, pleural effusion, ascites.

    - For Phase I: For treatment-experienced patients, the following washout periods are
    required prior to enrollment on the study: 2 weeks wash out after prior local therapy
    (such as radiation therapy or intra-lesional therapy), 4 weeks wash out after
    cytotoxic therapy or high dose interleukin-2, and 6 weeks wash out after anti-PD-1 or
    anti-PD-L1 therapy. For all other therapy not mentioned, a wash out period of at
    least 5 half lives will be needed.

    - For phase II: Histological diagnosis of BRAF V600E/K melanoma, unresectable stage III
    or stage IV, according to the AJCC Staging Manual, 7th Edition, 2011. Must have
    measurable disease, and no prior systemic treatment for locally advanced or
    metastatic melanoma. Previous local therapy is allowed. Previous systemic treatment
    for any stage III disease that was subsequently rendered NED (no evidence of disease)
    by surgery is allowed except for ipilimumab and BRAF inhibitors. Patients with
    resectable disease who do not want surgery for any reason are also allowed.
    Measurable disease is defined as least one lesion that can be accurately measured in
    two dimensions with both diameters greater than 1.0cm. For CT/MRI evaluations, an
    effective slice thickness is required of less than or equal to 5 mm. For slice
    thickness greater than 5mm, both diameters must be greater than or equal to 2.0cm at
    baseline.

    - ECOG performance status 0, 1 or 2

    - Negative pregnancy test for women of childbearing potential within 7 days of starting
    study treatment.

    - Lab testing results in accordance with protocol WBC greater/equal to 2,000/mm3 ANC
    greater/equal to 1200/mm3 Platelet greater/equal 1000,000/mm2 Hemoglobin
    greater/equal 9 gm/dL (may be transfused) Serum bilirubin levels less/equal 1.5 mg/dL
    except for patients with Gilbert's syndrome.

    - Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) less/equal
    2.5 X upper limit of normal Alkaline phosphatase less/equal 2.5 times upper limit of
    normal Serum Creatinine levels less/equal 1.5 mg/dL Left Ventricular Ejection
    Fraction (LVEF) greater or equal to lower limit of normal by ECHO Women of
    childbearing potential should be advised to avoid becoming pregnant and men should be
    advised to not father a child while receiving treatment with ipilimumab or
    dabrafenib. Patients should agree to use an appropriate method of birth control while
    on study.

    - Age greater than 18 years and of any gender or race. Able to provide informed consent
    and have signed an approved consent form that conforms to federal and institutional
    guidelines.

    Exclusion Criteria:

    - Concurrent therapy with any other non-protocol anti-cancer therapy

    - Prior systemic treatments with either ipilimumab or a BRAF inhibitor (such as
    vemurafenib or dabrafenib).

    - Prior local therapy within 2 weeks (for both phases I and II) or prior systemic
    therapy within 4 weeks of starting protocol treatment (phase I).

    - For phase II: Any prior systemic therapy for locally advanced or metastatic melanoma.
    Prior local therapy such as radiation or intratumoral injection is allowed. Previous
    systemic treatment for any stage III disease that was subsequently rendered NED (no
    evidence of disease) by surgery is allowed.

    - Brain metastases (except if all known lesions were previously treated with surgery or
    stereotactic radiosurgery and lesions, if still present, are confirmed stable for
    greater than or equal to 2 weeks prior to enrollment, and are asymptomatic with no
    corticosteroid requirements for greater than or equal to weeks prior to
    randomization, and no enzyme inducing anticonvulsants for greater than or equal to 2
    weeks prior to randomization). Brain MRI or CT is required at screening.

    - Anyone with a second malignancy expected to require cytotoxic chemotherapy or immune
    modulating therapy within 3 months of enrollment

    - Pre-existing autoimmunity: History of inflammatory bowel disease; history of
    symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive
    sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g.,
    Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g.,
    Guillain-Barre Syndrome). Subjects with vitiligo, type I diabetes mellitus, residual
    hypothyroidism due to autoimmune condition only requiring hormone replacement,
    psoriasis not requiring systemic treatment, or conditions not expected to recur in
    the absence of an external trigger are permitted to enroll.

    - No concurrent systemic corticosteroids (or other systemic immunosuppressant's),
    including oral steroids (i.e. prednisone, dexamethasone), continuous use of topical
    steroid creams or ointments, or ophthalmologic steroids. If a subject is currently
    taking corticosteroids, treatment should be discontinued two weeks prior to starting
    protocol therapy. Occasional use of steroid inhalers is allowed.

    - Any serious or uncontrolled medical disorder or active infection that, in the opinion
    of the investigator, may increase the risk associated with study participation, study
    drug administration, or would impair the ability of the subject to receive protocol
    therapy.

    - Any known positive test for hepatitis B virus or hepatitis C virus indicating acute
    or chronic infection. Known history of testing positive for human immunodeficiency
    virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

    - Herbal remedies (e.g., St. John's wort) within 1 week of enrollment.

    - Drugs that are strong inhibitors or inducers of CYP3A or CYP2C8, p-glycoprotein (Pgp)
    or Bcrp transporter because they may alter dabrafenib concentrations. The list may be
    modified based on emerging data; consider therapeutic substitutions for these
    medications. Patients must be off treatment for at least 1 week prior to enrollment.

    - A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency.

    - The presence of any other medical or psychiatric disorder that, in the opinion of the
    treating physician, would contraindicate the use of the drugs in this protocol or
    place the subject at undue risk for treatment complications

    - Pregnancy or breast feeding

    - A history of a severe hypersensitivity reaction to ipilimumab or dabrafenib

    - Any reason why, in the opinion of the investigator, the patient should not
    participate

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Safety of ipilimumab and dabrafenib in combination

    Secondary Outcome Measures

    Trial Keywords