Compassionate Use Program BRAF Mutation-positive Patients in the Adjuvant Treatment of Melanoma After Surgical Resection

NCT04544202 | Unknown

• 1 other identifier: CDRB436F2001CM
• Study Type: expanded_access
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this Treatment Plan is to allow access to trametinib and dabrafenib for eligible high-risk BRAF mutation-positive patients in the adjuvant treatment of melanoma after surgical resection. The patient's Treating Physician should follow the suggested treatment guidelines and comply with all local health authority regulations.

Conditions

Melanoma; Adjuvant

Keywords

Melanoma; Adjuvant; BRAF V600; Malignant skin cancer; Skin cancer; Stage III melanoma; Cutaneous; Resection; Surgical resection; Mutation; Compassionate Use; Dabrafenib; Trametinib; DRB436; TMT212; Cohort

Interventions

Dabrafenib and Trametinib DRUG

The starting dose of the combination treatment will be administered as follows: * Dabrafenib, 150 mg, twice daily (BID); * Trametinib, 2.0 mg, once daily (QD)

Dabrafenib DRUG

If administration of dabrafenib is interrupted or permanently discontinued, administration of trametinib may continue.

Trametinib DRUG

If administration of trametinib is interrupted or permanently discontinued, administration of dabrafenib may be continued.

Eligibility Criteria

• Age: 1 Year - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Has or is willing to give consent to the Treating Physician in accordance with the local regulatory requirements.
• Has the following diagnosis: Completely resected (R0) histologically confirmed high-risk (stage III) cutaneous melanoma with confirmed BRAF V600E/K activating mutation.
• Patients presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible. Patients with an unknown primary melanoma are not eligible.
• All clinical trials that the patient might qualify for have been ruled out.
• Is receiving care at a clinical site with a Treating Physician who has experience with administering investigational agents for patients with this condition, or the patient is willing and/or able to travel to a site and receive treatment under the guidance of physician with this experience.
• Is able to retain oral medication and swallow tablets/capsules (appropriate exceptions allowed for patients who are unable to swallow tablets/capsules - this is subject to availability of alternative (liquid) oral formulations).
• Is not eligible for participation in any of the IMP's ongoing clinical trials or has recently completed a clinical trial that has been terminated and, after considering other options (e.g., trial extensions, amendments, etc.), the clinical team has determined that treatment is necessary and there are no other feasible alternatives for the patient.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 3 (or equivalent) and is in stable clinical condition. NOTE: patient in rapidly deteriorating clinical condition prior to start of therapy should not be considered for this program.
• Does not require treatment with prohibited concomitant medications (please refer to the IB or approved label/SmPC).
• Women of childbearing potential must have had a negative serum β-human chorionic gonadotropin (HCG) pregnancy test within 7 days prior to starting dabrafenib and trametinib treatment. Subjects with a positive pregnancy test result must be excluded from the program. Subjects with a negative pregnancy test result must agree to use an effective contraception method as described below throughout the treatment period and for a total of 4 months following the last dose of treatment.
• Contraceptive Methods for Females of Childbearing Potential:
• An intrauterine device with a documented failure rate of less than 1% per year
• Vasectomized partner who is sterile prior to the female patient's entry into the Compassionate Use program, and this male is the sole sexual partner for that female.
• Complete abstinence from sexual intercourse for 14 days prior to first dose of treatment, through the dosing period, and for at least 4 months after the last dose of treatment. Abstinence is only acceptable when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.
• Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with vaginal spermicidal agent (foam/gel/cream/suppository).

You may not qualify if:

• Patients eligible for this Treatment Plan must not meet any of the following criteria:
• History of hypersensitivity to any drugs or metabolites of similar chemical classes as the product.
• Uveal or mucosal melanoma.
• Evidence of metastatic disease.
• Female who is pregnant or nursing (patient must discontinue nursing in order to enroll in the program).
• Patients who have any lab abnormalities or AE/SAEs greater than Grade 3 (CTCAE v5.0)
• Concurrent treatment with other systemic anti-cancer therapies is not allowed, with the exception of surgery (other exceptions might be allowed and are subject to individual evaluation). Patients who are currently being treated with another systemic anti-cancer therapy (e.g., chemotherapy, immune, biologic, or targeted therapy) must discontinue use prior to initiation of treatment with trametinib and dabrafenib. NOTE: Radiation skin injury has been reported with concurrent use of dabrafenib and radiation.
• Presence of any malignancy with confirmed activating RAS mutation. NOTE: Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility.
• Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib or dabrafenib, or excipients or to dimethyl sulfoxide (DMSO).
• Any medical conditions or physical examination or clinical laboratory findings which, would put the patient at high risk for an adverse outcome.
• Current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy.
• Current evidence of cardiovascular risk including any of the following:
• LVEF\<LLN
• A QT interval corrected for heart rate using the Bazett's formula ≥ 480 msec
• A clinically significant uncontrolled arrhythmias

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: expanded access
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2020
• First Posted: September 10, 2020
• Last Updated: November 12, 2024

Record last verified: 2024-11