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Advanced BRAF Mutant MelanomaPhase 1/2BAMMNCT02257424

Dabrafenib, Trametinib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma

A Phase 1/2 study testing Trametinib 2 mg daily, hydroxychloroquine (HCQ) and dabrafenib 150 mg orally twice a day in people with Advanced BRAF Mutant Melanoma, run by Abramson Cancer Center at Penn Medicine at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary purpose of this study is to determine the maximum tolerated dose (MTD) and preliminary safety of hydroxychloroquine (HCQ) when administered in conjunction with oral dabrafenib and trametinib (D+T) in patients with advanced BRAF mutant melanoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced BRAF Mutant Melanoma
What is being tested?
Trametinib 2 mg daily, hydroxychloroquine (HCQ) and dabrafenib 150 mg orally twice a day
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
4 sitesUnited States
Study dates
Oct 2014to Oct 2021
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must be at least 18 years of age.
  • Patients must have histologically confirmed melanoma unresectable Stage III or Stage IV positive for BRAF V600E, V600K, V600R or V600D by a CLIA approved assay.
  • Patients must have an ECOG performance status of 0 or 1.
  • Patients must have adequate baseline organ function as determined by table 2.
  • Table 2. Definitions for adequate baseline organ function
  • Laboratory Values
Show all 28Show fewer
  • Hematologic:
  • ANC (absolute neutrophil count) ≥1.2 × 109/L
  • Hemoglobin ≥ 9 g/dL
  • Platelet count ≥100 x 109/L
  • PT/INR and PTT ≤ 1.3 x ULN (PT = prothrombin time; INR = international normalized ratio; PTT = partial thromboplastin time; ULN = upper limit of normal)
  • Hepatic
  • Total bilirubin ≤ 1.5 x ULN
  • AST (aspartate aminotransferase) and ALT (alanine transaminase) ≤ 2.5 x ULN
  • Renal -- Serum creatinine ≤ 1.5 mg/dL
  • Cardiac
  • -- Left Ventricular Ejection fraction (LVEF) ≥ LLN (lower limit of normal) by ECHO
  • Subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to randomization.
  • If serum creatinine is > 1.5 mg/dL, calculate creatinine clearance using standard Cockcroft-Gault formula. Creatinine clearance must be ≥ 50 mL/min to be eligible.
  • Except subjects with known Gilbert's syndrome. ECHO scans must be used throughout the study when indicated
  • Patients must be able to provide written informed consent.
  • Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for ≥ 1 year. Women must use an effective method of contraception from 14 days prior to randomization, throughout the treatment period, and for at least 6 months after the last dose of study treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, or intra-uterine devices). At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.) Hormonal-based methods (e.g., oral contraceptives) are NOT permitted as contraception due to potential drug-drug interactions with dabrafenib.
  • Patients with brain metastases treated with whole brain radiation that have been stable for 2 months are eligible; patients with brain metastases treated with gamma knife or surgery are allowed to participate after 2 weeks have elapsed since their procedure. Subjects are excluded if they have leptomeningeal or metastases causing spinal cord compression that are symptomatic or untreated or not stable for ≥3 months (must be documented by imaging) or requiring corticosteroids. Subjects on a stable dose of corticosteroids >1 month or who have been off of corticosteroids for at least 1 week can be enrolled with approval of the medical monitor
  • Any number and type of prior anticancer therapies are allowed except BRAF or MEK inhibitors .
  • Patients must have discontinued active immunotherapy (IL-2, interferon, CTLA-4, etc.) or chemotherapy at least 4 weeks prior to entering the study and oral targeted therapy at least 2 weeks prior to entering the study. Patients must not receive any other investigational anticancer therapy during the period on study or the four weeks prior to entry.
  • All prior anti-cancer treatment-related toxicities (except alopecia and laboratory values as listed in Eligibility Criteria #4) must be Grade 1 according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.03, 2009) at the time of starting treatment. Patients that are asymptomatic on low dose maintenance hormone replacement delivered at a stable dose for prior toxicities are eligible.
  • Patient much have measurable disease as defined by RECIST 1.1.
  • Patients must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.

Who cannot join

  • Patients with known serious concurrent infection or medical illness, including psychiatric disorders, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
  • Patients who are pregnant or breast-feeding.
  • Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents).
  • Patients who are known to be experiencing an objective partial response to immunotherapy at the time of study enrollment
  • History of malignancy other than disease under study within 3 years of study enrollment with exceptions below:
  • Exception: Subjects with a history of completely resected non-melanoma skin cancer, or subjects with indolent second malignancies are eligible
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  • History of malignancy with confirmed activating RAS mutation at any time. Note: Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility.
  • History of interstitial lung disease or chronic pneumonitis
  • Due to risk of disease exacerbation patients with porphyria or psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations.
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).
  • Patients receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (EIADs) (i.e. phenytoin, carbamazepine, Phenobarbital, primidone or oxcarbazepine) within 4 weeks of the start of the study treatment
  • Current use of a prohibited medication as described in Section 6.3.8 of the protocol for Potential for Drug-Drug Interaction: apply moisturizing creams frequently, topical keratolytics (e.g. urea 20-40 % cream, salicylic acid 6%, tazarotene 0.1% cream, fluorouracil 5% cream), clobetasol propionate 0.05% ointment for erythematous areas, topical lidocaine 2%, and / or systemic pain medication such as nonsteroidal anti-inflammatory drugs, codeine, and pregabalin for pain.
  • Known Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and/or HCV will be permitted
  • Patients with a previously documented retinal vein occlusion.
  • History or evidence of increased cardiovascular risk including any of the following
  • Left ventricular ejection fraction (LVEF) < institutional lower limit of normal.
  • A QT interval corrected for heart rate using the Bazett's formula ≥ 480 msec;
  • Current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation for >30 days prior to randomization are eligible.
  • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization.
  • Current ≥ Class II congestive heart failure as defined by New York Heart Association
  • Patients with intra-cardiac defibrillators
  • Abnormal cardiac valve morphology (≥grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Robert H. Lurie Comprehensive Cancer Center

    Chicago, Illinois, 60611

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Abramson Cancer Center of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: BRAF, Autophagy and MEK Inhibition in Metastatic Melanoma: A Phase I/II Open-Label Trial of Dabrafenib, Trametinib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma

The primary purpose of this study is to determine the maximum tolerated dose (MTD) and preliminary safety of hydroxychloroquine (HCQ) when administered in conjunction with oral dabrafenib and trametinib (D+T) in patients with advanced BRAF mutant melanoma.

Being tested
Trametinib 2 mg daily, hydroxychloroquine (HCQ), dabrafenib 150 mg orally twice a day

What participants receive

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

  • Trametinib 2 mg dailyDrug

  • hydroxychloroquine (HCQ)Drug

    hydroxychloroquine (HCQ) is 600 mg orally every 12 hours

  • dabrafenib 150 mg orally twice a dayDrug

Study groups in NCT02257424
Study groupRoleWhat they receive
Phase 1/2OtherNot described
Receives: Drug: Trametinib 2 mg daily; Drug: hydroxychloroquine (HCQ); Drug: dabrafenib 150 mg orally twice a day

What is being measured

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

  1. Phase 1: To determine the maximum tolerated dose

    Phase 1: Maximum tolerated dose (MTD) = a) the dose producing Dose Limiting Toxicity (DLT) in 2/6 patients, or b) the dose level below the dose which produced DLT in ≥ 2/3 patients, or in ≥ 3/6 patients

    Measured: 5 weeks

  2. Phase 2: To assess the clinical efficacy of HCQ+D+T by 1 year PFS rate.

    Phase 2: Progression free survival (PFS) is defined as the duration of time from start of treatment to time of first progression, death due to any cause or last patient contact alive and progression-free

    Measured: 1 year

Timeline

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

  1. First posted6 Oct 2014 (estimated)
  2. Study startOct 2014
  3. Primary completionOct 2021
  4. Study completionOct 2021

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02257424
Sponsor's protocol ID
UPCC 02614
Acronym
BAMM
Status last verified
Jan 2022
First submitted
2 Oct 2014
Last updated
20 Jan 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • Amaravadi RK. Clinical trial results show promise of targeting autophagy BRAF mutant melanoma. Autophagy. 2022 Jun;18(6):1470-1471. doi: 10.1080/15548627.2022.2038899. Epub 2022 Feb 13.

    PubMed 35156519

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Trametinib 2 mg daily, hydroxychloroquine (HCQ) and dabrafenib 150 mg orally twice a day in people with Advanced BRAF Mutant Melanoma, run by Abramson Cancer Center at Penn Medicine at 4 sites 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 28 inclusion and 22 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: finished, as of the sponsor's last update on 20 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Phase 1: To determine the maximum tolerated dose (time frame: 5 weeks). The study lists 2 primary outcomes in all. 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 NCT02257424, which also lists 1 linked publication.

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 20 Jan 2022.

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