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

NCT02257424 | Completed Phase 1 DMC

• 1 other identifier: UPCC 02614
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Advanced BRAF Mutant Melanoma

Outcome Measures

Primary Outcomes (2)

• 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

  5 weeks

• 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

  1 year

Study Arms (1)

Phase 1/2

OTHER

Drug: Trametinib 2 mg daily; Drug: hydroxychloroquine (HCQ); Drug: dabrafenib 150 mg orally twice a day

Interventions

Trametinib 2 mg daily DRUG

Phase 1/2

hydroxychloroquine (HCQ) DRUG

hydroxychloroquine (HCQ) is 600 mg orally every 12 hours

Phase 1/2

dabrafenib 150 mg orally twice a day DRUG

Phase 1/2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (4)

Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 35156519 DERIVED

MeSH Terms

Interventions

trametinib; Hydroxychloroquine; dabrafenib

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ravi Amaravadi, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2014
• First Posted: October 6, 2014
• Study Start: October 1, 2014
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: January 20, 2022

Record last verified: 2022-01

Locations

US (4)