NCI Community Oncology Research Program - Kansas City (NCORP-KC)
NCI Community Oncology Research Program - Kansas City (NCORP-KC)




NCI Community Oncology Research Program - Protocol Summary

SWOG S1320 - "A Randomized, Phase II Trial of Intermittent Versus Continuous Dosing of Dabrafenib (NSC-763760) and Trametinib (NSC-763093) in BRAFV600E/K Mutant Melanoma."

The summary below serves as a brief review of the treatment plan and eligibility for the protocol.


This summary is not intended to be used in place of the full eligibility & treatment information in the protocol.
 

Please follow the "Full Protocol" link or contact NCORP-KC for complete protocol information.



Print This Summary

Skin Clinical Trial

CANCER TYPE: Melanoma
RESEARCH BASE: SWOG
NCT NUMBER: 02196181
HIPPA FORM: DOWNLOAD HIPPA FORM

Consent Form: VIEW CONSENT FORM

BRIEF DESCRIPTION

Melanoma, Stg IV; intermittent vs continuous dosing of dabrafenib and trametinib



NOTES


Treatment Plan   (Supplied Drug:  Dabrafenib and Trametinib)

One cycle = 56 days

 

Step 1: Continuous Treatment Lead-In:
Dabrafenib 150 mg PO twice daily Continuous for 56 days
Trametinib 2 mg PO daily Continuous for 56 days

Patients must not have unequivocal disease progression (by RECIST v1.1) during the first cycle.

Patients must be registered to Step 2: Randomization within +/- 5 days of starting Cycle 2. Patients MUST NOT be registered prior to the Day 56 Disease Assessment

 

Step 2: Randomization:

Arm 1: Continuous Treatment

Dabrafenib 150 mg PO twice daily Continuous for 56 days

Trametinib 2 mg PO daily Continuous for 56 days

Arm 2: Intermittent Treatment

Dabrafenib 150 mg PO twice daily Days 1-7 and 29-56

Trametinib 2 mg PO daily Days 1-7 and 29-56

**There is no drug administered on days 8-28

 

Treatment will continue until:  progression, symptomatic deterioration, unacceptable toxicity, tx delay > 14 days

 



ELIGIBILITY

  • Histologically or cytologically confirmed Stage IV or unresectable Stage III BRAFV600E or BRAFV600K mutant melanoma.
  • Contrast-enhanced CT scans of the neck, chest, abdomen and pelvis are required. Patients must have measurable disease per RECIST 1.1.
  • No prior BRAF or MEK inhibitor.
  • No brain metastases unless brain metastases have been treated and patient is asymptomatic with no residual neurological dysfunction and has not received enzyme-reducing anti-epileptic drugs or corticosteroids for at least 7 days prior to registration.
  • No anti-cancer drug within 28 days prior to registration, and must not have received any nitrosureas or mitomycin C within 42 days prior to registration.
  • No major surgery, or immunotherapy within 28 days prior to registration.
  • No unresolved toxicity greater than NCI-CTCAE v4.0 Grade 1 from previous anti-cancer therapy except alopecia within 7 days prior to registration.
  • Age ≥ 18 years of age.
  • Must have adequate bone marrow function as evidenced by all of the following: ANC ≥ 1,200/μl; platelets ≥ 100,000/μl; and hemoglobin ≥ 9 g/dL.
  • Must have adequate liver function as evidenced by the following: total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (or ≤ 2.5 x ULN with Gilbert’s Syndrome), and AST and ALT ≤ 2.5 x IULN (or < 5 x IULN for patients with known liver metastases). Patients must have a serum albumin ≥ 2.5 g/dL.
  • Must have adequate renal function as evidenced by any ONE of the following: serum creatinine ≤ 1.5 mg/dL OR measured or calculated creatinine clearance ≥ 50 mL/min. 
  • Must have LDH obtained within 28 days prior to registration in order to obtain baseline stratification information.
  • Must have a left ventricular ejection fraction (LVEF) ≥ institutional lower limit of normal (ILLN) by ECHO or MUGA within 28 days prior to registration.
  • Must have QTc ≤ 480 msec by ECG (corrected using the Bazett’s formula) within 28 days prior to registration.
  • Patients with known history or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible:
    • History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).
    • Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:
      • Evidence of new optic disc cupping
      • Evidence of new visual field defects
      • Intraocular pressure > 21 mmHg
    • NOTE: Ophthalmic exam is required for all patients. Exam must be obtained within 28 days prior to registration.
  • Must be able to take oral medications.  Must not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of protocol treatment (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
  • Patients receiving anticoagulation treatment are allowed to participate with INR established within the therapeutic range.
  • No history of pneumonitis or interstitial lung disease.
  • No Grade II/III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia (see Appendix 18.2.). Abnormal cardiac valve morphology (≥ Grade 2) documented by echocardiogram (subjects with Grade 1 abnormalities [i.e., mild regurgitation/stenosis]) can be entered on study. Patients with a history of atrial fibrillation must have atrial fibrillation controlled for at least 30 days prior to registration
  • Patients with known Hepatitis B or Hepatitis C are not eligible.  Patients with known HIV may be eligible providing they meet the following additional criteria:
    • CD4 cells ≥ 500/uL
    • Serum HIV viral load of < 25,000 IU/ml
    • No current antiretroviral therapy
    • Tests must be obtained within 28 days prior to registration. Patients who are HIV+ and do not meet all of these criteria are not eligible for this study.  (HIV/Hepatitis testing are not required for patients without known infection.)
  • Must have dermatology exam obtained within 28 days prior to registration to obtain baseline measurement. Exam to be performed by treating physician or designated dermatologist.
  • Zubrod Performance Status of 0 or 1.
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years. Exception: Patients with known history of colon cancer, cancer of the pancreas, or any cancer known to harbor an activating RAS mutation are ineligible regardless of stage or time since diagnosis.
  • Not pregnant or nursing because of the risk of fetal harm. Women/men of reproductive potential must have agreed to use an effective contraceptive method.
  • Must be offered the opportunity to participate in specimen banking.
  • Signed informed consent.





  © 2013-2018 All Rights Reserved. Privacy Policy | Terms & Conditions
NCI Community Oncology Research Program - Kansas City (NCORP-KC)
Questions? Call: +1-913-948-5588 | Contact Us
4121 W. 83rd St., Suite 259 Prairie Village, KS 66208 USA