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Vemurafenib and TIL Therapy for Metastatic Melanoma

Study Purpose

Background: Adoptive T cell therapy with tumor infiltrating lymphocytes (TILs) has been reported to induce durable clinical responses in patients with metastatic melanoma. From patients own tumor material T cells are extracted, expanded and activated in vitro in a 4-6 weeks culture period. Before TIL infusion patients are preconditioned with a lymphodepleting chemotherapeutic regimen. After TIL infusion, patients are treated with IL-2 to support T cell activation and expansion in vivo. The BRAF inhibitor is an approved treatment of metastatic melanoma and functions by selectively inhibiting the BRAF mutated enzyme, consequently halting the proliferation of tumor cells. Furthermore, in vitro tests have shown that vemurafenib has immunomodulatory effects that are hypothesized to synergize with TIL therapy, which has been confirmed in animal studies. Objectives:

  • - To evaluate safety and feasibility when combining vemurafenib and ACT with TILs.
  • - To evaluate treatment related immune responses - To evaluate clinical efficacy Design: - Patients will be screened with a physical exam, medical history, blood samples and ECG.
  • - Patients will start vemurafenib 960 mg BID and will continue during TIL preparation.
  • - 7 days after start of vemurafenib, patients will undergo surgery to harvest tumor material for TIL production.
  • - Patient stops vemurafenib and is admitted day -8 in order to undergo lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7.
  • - On day 0 patients receive TIL infusion and shortly after starts IL-2 infusion continually following the decrescendo regimen.
  • - The patients will followed until progression or up to 5 years.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

 No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

 Interventional
Eligible Ages 18 Years - 70 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Histologically confirmed unresectable stage III or stage IV metastatic melanoma.
  • - Metastasis available for surgical resection (about 2 cm3) and residual measureable disease after resection.
  • - Pathologically verified BRAF mutation.
  • - ECOG performance status 0-1.
  • - Life expectancy ≥ 3 months.
  • - No significant toxicity (CTC ≤ 1) from prior treatments.
  • - Adequate renal, hepatic and hematologic function.
  • - Women of childbearing potential (WOCBP) and men in a sexual relationship with a WOCBP must be using an effective method of contraception during treatment and for at least 6 months after completion of treatment.
  • - Able to comprehend the information given and willing to sign informed consent.

Exclusion Criteria:

  • - Other malignancies, unless followed for ≥ 5 years with no sign of disease, except squamous cell carcinoma or adequately treated carcinoma in situ colli uteri.
  • - Cerebral metastasis.
Patients with previously treated CNS metastasis can participate if surgically removed or treated with stereotactic radiotherapy if stable > 28 days after treatment measured by MRI. Patients with asymptomatic and untreated CNS metastasis can participate based on investigators evaluation.
  • - Patients with ocular melanoma.
  • - Previous treatment with a BRAF inhibitor.
  • - Severe allergies, history of anaphylaxis or known allergies to drugs administered.
  • - Serious medical or psychiatric comorbidity.
  • - QTc ≥ 450 ms.
  • - Clearance < 70 ml/min.
  • - Acute or chronic infection with e.g. HIV, hepatitis, tuberculosis - Active autoimmune disease.
  • - Pregnant og nursing women.
  • - Need for immunosuppressive treatment, e.g. corticosteroids or methotrexate.
  • - Concomitant treatment with other experimental drugs.
- Patients with uncontrolled hypercalcemia - More than four weeks must have elapsed since any prior systemic therapy at the time of treatment

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

 NCT02354690
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

 Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

 Inge Marie Svane
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

 Inge Marie Svane, Prof., MDTroels Holz Borch, MD
Principal Investigator Affiliation Department of Oncology, Copenhagen University Hospital, Herlev, Herlev Ringvej 75, DK-2730 Herlev, DenmarkDepartment of Oncology, Copenhagen University Hospital, Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

 Other
Overall Status Recruiting
Countries Denmark
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

 Metastatic Melanoma

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Copenhagen, Herlev, Denmark

Status

Recruiting

Address

Center for Cancer Immune Therapy, Dept. of Haematology/Oncology

Copenhagen, Herlev, 2730

Site Contact

Inge Marie Svane, Prof, MD

inge.marie.svane@regionh.dk

+45 38683868

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