Dabrafenib, Trametinib, and Spartalizumab for the Treatment of BRAF V600E or V600K Mutation Positive Stage IIIB/C/D Melanoma

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-29

Study Completion Date

2023-10-09

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This phase II trial studies how well dabrafenib, trametinib, and spartalizumab works in treating patients with BRAF V600E or V600K mutation positive stage IIIB/C/D melanoma, who do not achieve a pathologic complete response after 8 weeks of dabrafenib and trametinib treatment. Patients who achieve a pathologic complete response after 8 weeks of neoadjuvant dabrafenib and trametinib will receive adjuvant dabrafenib and trametinib. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as spartalizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving dabrafenib, trametinib, and spartalizumab may help to control melanoma.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery

NCT01701037

Recurrent Melanoma Stage IIB Melanoma (Locally Advanced) Stage IIC Melanoma (Locally Advanced) +4 more

TERMINATED PHASE2

Dabrafenib and Trametinib Before and After Surgery in Treating Patients With Stage IIIB-C Melanoma With BRAF V600 Mutation

NCT02231775

Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7

ACTIVE_NOT_RECRUITING PHASE2

Testing Two Different Treatment Schedules of Dabrafenib and Trametinib for Skin Cancer Which Has Spread

NCT02196181

Stage III Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Unresectable Melanoma

ACTIVE_NOT_RECRUITING PHASE2

Testing the Addition of the Anti-cancer Drug, Tazemetostat, to the Usual Treatment (Dabrafenib and Trametinib) for Metastatic Melanoma That Has Progressed on the Usual Treatment

NCT04557956

Clinical Stage IV Cutaneous Melanoma AJCC v8 Metastatic Melanoma

ACTIVE_NOT_RECRUITING PHASE1/PHASE2

A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

NCT01584648

Melanoma

COMPLETED PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVE:

I. To determine the 12-month relapse free survival (RFS) rate in stage IIIB/C/D melanoma patients who, after 8 weeks of neoadjuvant dabrafenib and trametinib, do not achieve a pathologic complete response (pCR) and receive adjuvant dabrafenib, trametinib and spartalizumab.

SECONDARY OBJECTIVES:

I. To evaluate the safety of neoadjuvant dabrafenib and trametinib and adjuvant dabrafenib, trametinib and spartalizumab.

II. To determine the 12-month relapse free survival (RFS) rate in stage IIIB/C/D.

III. Melanoma patients who, after 8 weeks of neoadjuvant dabrafenib and trametinib, achieve a pCR and receive adjuvant dabrafenib and trametinib.

IV. To assess the recurrence patterns, distant metastasis-free survival (DMFS), and overall survival (OS) in all patients treated on protocol.

EXPLORATORY OBJECTIVES:

I. To assess immunological and molecular features of treatment response and resistance.

II. To assess circulating markers and correlate them with treatment response and relapse and toxicity III. To assess the impact of neoadjuvant therapy on surgical resectability.

OUTLINE:

NEOADJUVANT TREATMENT: Patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) on days 1-28. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.

SURGERY: Patients undergo surgical resection of melanoma.

ADJUVANT TREATMENT OF pCR PATIENTS: Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeats every 28 days for 44 weeks in the absence of disease progression or unacceptable toxicity.

ADJUVANT TREATMENT OF NON pCR PATIENTS: Patients receive spartalizumab intravenously (IV) over 30 minutes on day 1, dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeats every 28 days for 44 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-4 months for 2 years.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 Pathologic Stage IIID Cutaneous Melanoma AJCC v8

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (dabrafenib, trametinib, surgery, spartalizumab)

NEOADJUVANT TREATMENT: Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.

SURGERY: Patients undergo surgical resection of melanoma.

ADJUVANT TREATMENT OF pCR PATIENTS: Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeats every 28 days for 44 weeks in the absence of disease progression or unacceptable toxicity.

ADJUVANT TREATMENT OF NON pCR PATIENTS: Patients receive spartalizumab IV over 30 minutes on day 1, dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeats every 28 days for 44 weeks in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Dabrafenib

Intervention Type DRUG

Given PO

Spartalizumab

Intervention Type BIOLOGICAL

Given IV

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Trametinib

Intervention Type DRUG

Given PO

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Dabrafenib

Given PO

Intervention Type DRUG

Spartalizumab

Given IV

Intervention Type BIOLOGICAL

Therapeutic Conventional Surgery

Undergo surgery

Intervention Type PROCEDURE

Trametinib

Given PO

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

BRAF Inhibitor GSK2118436 GSK-2118436 GSK-2118436A GSK2118436 PDR-001 PDR001 GSK1120212 JTP-74057 MEK Inhibitor GSK1120212 Mekinist

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
* Patients must have histologically or cytologically confirmed clinically detected, node involved Stage IIIB/C/D melanoma by American Joint Committee on Cancer (AJCC) version 8 and surgically resectable disease. The definition of resectability can be determined by the patient's surgical oncologist and verified via discussion at multidisciplinary tumor conference attended by melanoma medical and surgical oncology staff. Resectable tumors are defined as having no significant vascular, neural or bony involvement that would preclude complete resection or necessitate the use of adjuvant radiation. Only cases where a complete surgical resection with tumor- free margins can safely be achieved are defined as resectable
* BRAF mutation-positive melanoma (V600E or V600K) based on report from a Clinical Laboratory Improvement Act (CLIA) certified laboratory
* Patients must have measurable disease, defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Patients who have been previously treated in the adjuvant setting with ipilimumab or interferon alpha or investigational vaccines for melanoma will be eligible for treatment after a 28 day wash-out period
* Patients who have previously received anti PD-1 in the adjuvant setting will be allowed if it has been six months or longer since previous drug exposure
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Women of childbearing potential, defined as all women physiologically capable of becoming pregnant will be required to use highly effective methods of contraception during dosing and for 150-days after stopping treatment with spartalizumab. Highly effective contraception methods include:

* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
* Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject
* Placement of a non-hormonal intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year
* Notes:

* Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/cream/suppository) are not considered highly effective methods of contraception.
* Hormonal-based methods (e.g., oral contraceptives) are not considered as highly effective methods of contraception due to potential drug-drug interactions with dabrafenib.
* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential
* Sexually active males must use a condom during intercourse while on treatment and for 150 days after stopping treatment with spartalizumab and should not father a child in this period. A condom is required to be used by vasectomized men as well during intercourse in order to prevent delivery of the drug via semen
* Absolute neutrophil count (ANC) \>= 1500/uL
* Platelets \>= 100,000/uL
* Hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/L

* Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 30 mL/min for participant with creatinine levels \> 1.5 x institutional ULN

* Creatinine clearance (CrCl) should be calculated per institutional standard
* Total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for participants with total bilirubin levels \> 1.5 x ULN
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x ULN
* International normalized ratio (INR) OR prothrombin time (PT) =\<1.5 x ULN unless participant is receiving anticoagulant therapy as long as prothrombin time (PT) or partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants
* Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria

* Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug within 28 days
* Evidence of metastatic melanoma or patients with only in-transit metastases without involved nodes
* Prior BRAF or MEK inhibitor use
* Prior anti PD-1 or anti PD-L1 inhibitor use in last 6 months
* Prior malignancy active within the previous 2 years except for patient's prior diagnosis of melanoma and locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast with local control measures (surgery, radiation)
* Subjects with active, known or suspected autoimmune disease. 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
* Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
* Any positive test result for hepatitis B or C and human immunodeficiency virus (HIV) virus indicating acute or chronic infection
* Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome
* History of severe hypersensitivity reaction to any monoclonal antibody
* History of Central serous retinopathy (CSR) or retinal vein occlusion (RVO), 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)
* Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs
* Corrected QT (QTc) interval \>= 480 msec (\>= 500 msec for subjects with bundle branch block)
* Uncontrolled arrhythmias
* Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
* Pregnant or lactating female
* Unwillingness or inability to follow the procedures required in the protocol
* Uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity
* Subjects with known glucose 6 phosphate dehydrogenase (G6PD) deficiency

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No