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Multicenter Phase 1b Trial Testing the Neoadjuvant Combination of Domatinostat, Nivolumab and Ipilimumab in IFN-gamma Signature-low and IFN-gamma Signature-high RECIST 1.1-measurable Stage III Cutaneous or Unknown Primary Melanoma

2019-10-24 12:49:21 | BioPortfolio

Summary

DONIMI is a phase 1b trial testing the combination of domatinostat + nivolumab or nivolumab monotherapy in IFN-gamma signature high patients and of domatinostat + nivolumab or domatinostat + nivolumab + ipilimumab in IFN-gamma signature low patients with de-novo or recurrent macroscopic stage III cutaneous or unknown primary melanoma.

The trial will include 40 stage III cutaneous or unknown primary melanoma patients with RECIST 1.1 measurable de-novo or recurrent disease (short axis lymph node metastasis ≥1.5cm).

IFN-gamma signature low patients will be randomized to be treated pre-surgically for 6 weeks with domatinostat + nivolumab or domatinostat + nivolumab + ipilimumab (each 10 patients).

NanoString IFN-gamma signature high patients will be randomized to be treated pre-surgically for 6 weeks with nivolumab or domatinostat + nivolumab (each 10 patients).

Post-surgery (starting at week 12), the patients will start with adjuvant nivolumab or pembrolizumab for 52 weeks according to institute's standard. BRAF V600E/K mutation positive patients with no pathologic response after neoadjuvant therapy may also receive adjuvant BRAF + MEK inhibition if commercially available and according to the patient's and the treating physician's decision.

Follow-up after the adjuvant therapy will be for 2 years, according to the institutes' standard.

Toxicity and pathologic response rates will be descriptive. In case of 2/5 or 4/10 patients not undergoing their lymph node dissection at week 6 +/- 1 week due to treatment related toxicity, this arm will be declared unfeasible.

Study Design

Conditions

Malignant Melanoma Stage III

Intervention

Domatinostat, Nivolumab, Ipilimumab

Location

Antoni van Leeuwenhoek Hospital
Amsterdam
Netherlands
1066CX

Status

Not yet recruiting

Source

The Netherlands Cancer Institute

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-10-24T12:49:21-0400

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Medical and Biotech [MESH] Definitions

An unpigmented malignant melanoma. It is an anaplastic melanoma consisting of cells derived from melanoblasts but not forming melanin. (Dorland, 27th ed; Stedman, 25th ed)

Tumors of the iris characterized by increased pigmentation of melanocytes. Iris nevi are composed of proliferated melanocytes and are associated with neurofibromatosis and malignant melanoma of the choroid and ciliary body. Malignant melanoma of the iris often originates from preexisting nevi.

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A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.

A cellular subtype of malignant melanoma. It is a pigmented lesion composed of melanocytes occurring on sun-exposed skin, usually the face and neck. The melanocytes are commonly multinucleated with a "starburst" appearance. It is considered by many to be the in situ phase of lentigo maligna melanoma.

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