Circulating Tumour DNA guidEd Therapy for Stage IIB/C mElanoma After surgiCal resecTION

NCT04901988 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: CFTSp135
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The trial is looking for new and better ways to treat melanoma, an aggressive type of skin cancer. Having surgery to remove the melanoma will cure the majority of patients with early stage disease. However, a small percentage of these patients will go on to develop further disease, which may spread to other places in their body. Currently, patients who have been cured of melanoma will have appointments in clinic to check that further disease has not developed or returned and some may also receive regular scans. The trial team has developed a blood test that tells us whether cancer cells are still present or is becoming active after a patient has been 'cured' of melanoma, even if a scan looks normal. The test looks for pieces of DNA in the blood that are known to have come from the cancer, which we call 'circulating tumour DNA', or ctDNA. Patients who have ctDNA in their blood have an extremely high chance of the cancer returning. By using the blood test that we have developed we think that we can identify patients earlier than normal. We think that some of the treatments that are used when melanoma cancer has spread may benefit patients at this earlier stage. We want to see if these patients with ctDNA in their blood, who have a higher risk of their cancer returning or spreading, and receive treatment early have a better response to their cancer compared to those patients who receive treatment when their cancer has returned and it can be seen on a scan. This could mean we would be able to offer patients earlier treatment in the future using just a blood test rather than a scan, while also providing reassurance to those patients that do not have ctDNA in their blood that they do not need treatment and their cancer is not returning.

Conditions

Melanoma (Skin); Melanoma, Stage II

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  From randomisation until death by any cause, assessed up to 84 months.

Secondary Outcomes (13)

• Relapse Free Survival

  From randomisation to radiological (recist v1.1)/clinical (confirmed histologically) progression, assessed up to 84 months.

• Distant metastasis free survival(DMFS)

  From randomisation to distant metastatic relapse or death, assessed up to 84 months.

• Progression-free survival (PFS) on first line therapy (commenced in Arm A at relapse, and Arm B from randomisation).

  From start of treatment (day of first dose) until disease progression defined as clinical (confirmed pathologically) or radiological (recist v1.1) progression or death, assessed up to 84 months.

• Time from randomisation to disease progression on first line systemic therapy (Arm A first systemic therapy given at relapse, and Arm B nivolumab from randomisation).

  Time from randomisation to disease progression on first line systemic therapy (Arm A first systemic therapy given at relapse, and Arm B nivolumab from randomisation), assessed up to 84 months.

• Radiological response in Arm A (CR, PR, SD and PD) and PD vs. no PD in Arm B to first line systemic therapy.

  Radiological response in Arm A (CR, PR, SD and PD) and PD vs. no PD in Arm B to first line systemic therapy, assessed up to 84 months.

Study Arms (2)

Arm A

NO INTERVENTION

In Arm A, patients and clinicians will remain blinded to the ctDNA result and will be managed as per standard of care with regular clinical review and imaging, and treated if they develop evidence of disease recurrence.

Arm B

EXPERIMENTAL

Patients randomised to Arm B will not be blinded to the positive ctDNA result and will be treated with the intervention.

Drug: Nivolumab 10 MG/ML

Interventions

Nivolumab 10 MG/ML DRUG

Eligible patients randomised to Arm B will receive 480 mg nivolumab monotherapy 4 weekly via IV infusion for up to 2 years.

Arm B

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent.
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
• Histological confirmation of cutaneous melanoma
• ≥ 18 years.
• Stage IIB or IIC melanoma (sentinel lymph node (SNLB) staged) according to AJCC version 8 (4).
• Complete resection (including SNLB) must have been performed within 12 weeks prior to registration.
• Disease-free status documented both clinically and radiologically within 4 weeks prior to registration.
• Mutation confirmed in at least one of the following BRAF (p.V600E/p.V600K/p.V600R) /NRAS (p.Q61R/p.Q61K, p.Q61L/p.G12D), which can be tracked in ctDNA with exact point mutation known.
• ECOG performance status 0/1.
• Adequate organ function and screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Absolute neutrophil count (ANC) ≥1.5x109/L, Platelets ≥100 x109/L, Haemoglobin ≥90 g/L, Creatinine ≤1.5x ULN or creatinine clearance \>30mL/minute using Cockcroft-Gault, AST ≤ 1.5 x ULN, ALT ≤ 1.5 x ULN, Bilirubin ≤1.5 x ULN unless the patient has familial hyperbilirubinaemia.
• LDH ≤1.5x ULN as per local institution parameters.
• Patients who are pregnant or breastfeeding will be eligible to join the trial. However, if they are allocated to Arm B, women of childbearing potential (WOCBP) must agree to have a serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) and must be withdrawn if pregnant or breastfeeding. WOCBP and males who are sexually active with WOCBP must also agree to follow instructions for method(s) of contraception for the duration of treatment plus 5 months for WOCBP or plus 7 months for males who are sexually active with WOCBP (if randomised to Arm B or while receiving any systemic treatment and to follow local guidance if given on Arm A). See Appendix A for further information.

You may not qualify if:

• If previously received prior immunotherapy, chemotherapy, cancer directed vaccine therapy or BRAF/MEK targeted therapy for cancer.
• Patients with active, known or suspected autoimmune disease. Patients with type 1 diabetes mellitus, rheumatoid arthritis not requiring disease modifying drugs, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger will be permitted to enrol.
• Current other malignancy or history of another malignancy within the last 3 years. Patients who have been disease-free for 3 years, (i.e. patients with second malignancies that have been definitively treated at least 3 years ago) or patients with a history of completely resected non-melanoma skin cancer are eligible.
• Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the patient's safety, obtaining informed consent, or compliance with study procedures.
• Patients with a condition requiring ongoing/long-term (\>3 months) systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications. Inhaled or topical steroids and adrenal replacement steroid doses ≤10 mg daily prednisolone equivalent are permitted in the absence of active autoimmune disease.
• Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• History of allergies or adverse drug reaction to any of the study drug components or to any monoclonal antibody.
• Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.
• Prisoners or patients who are involuntarily incarcerated.

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• University of Manchester: collaborator
• Manchester Academic Health Science Centre: collaborator
• University of Liverpool: collaborator

Study Sites (1)

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M204BJ, United Kingdom

Location

Related Links

• HRA summary of results- there are no study results due to early termination. See HRA summary link for more details.

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Paul Lorigan, Professor

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No participants were randomised prior to early termination.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2021
• First Posted: May 26, 2021
• Study Start: November 8, 2021
• Primary Completion: January 30, 2023
• Study Completion: January 30, 2023
• Last Updated: February 27, 2025

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Early termination of the study was declared prior to any patients being randomised which means we are unable to perform any evaluation of result or outcome.

Locations

GB (1)