Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Tin Fluorides

Immunomodulating Agents

Patients who relapsed after or were refractory to at least 1 prior line of systemic therapy including a PD-1 inhibitor.

Patients who were intolerant to a PD-1 inhibitor and have persistent disease after stopping PD-1 therapy.

Patients who had a best response of stable disease despite being treated with at least 4 doses of a PD-1 inhibitor in the previous line of therapy.

ITIL-168 is a cell therapy product derived from a patient's own TILs. A tumor sample is removed from each patient to make a personalized ITIL-168 product. Once ITIL-168 has been made, the patient is treated with 5 days of lymphodepleting chemotherapy including cyclophosphamide and fludarabine, followed by a single infusion of ITIL-168, and up to 8 doses of IL-2.

ITIL-168

Instil Study Director

DELTA-1 is a phase 2 clinical trial to evaluate the efficacy and safety of ITIL-168 in adult subjects with advanced melanoma who have previously been treated with a PD-1 inhibitor. ITIL-168 is a cell therapy derived from a patient's own tumor-infiltrating immune cells (lymphocytes; TILs).

All enrolled participants are assigned to be treated with a single dose of ITIL-168

ITIL-168 in Advanced Melanoma

A Phase 2, Open-label, Multicenter Study Evaluating the Safety and Efficacy of Autologous Tumor-infiltrating Lymphocytes (TILs) in Subjects With Advanced Melanoma (DELTA-1)

Objective response rate (ORR), defined as the incidence of a complete response (CR) or a partial response (PR) per a modified Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria, as assessed by central review.

For subjects who experience an objective response, duration of response (DOR) is defined as the time from their first objective response to disease progression or death.

Progression-free survival (PFS) is defined as the time from the ITIL-168 infusion date to the date of disease progression or death from any cause.

Overall survival (OS) is defined as the time from the ITIL-168 infusion date to the date of death from any cause.

ORR as determined by investigators is defined as the incidence of a CR or a PR per a modified RECIST v1.1, as determined by study investigators.

Disease control rate (DCR), defined as the incidence of CR, PR, or stable disease (SD) per a modified RECIST v1.1 criteria, as determined by central review.

Instil Bio

Ipilimumab

Bristol-Myers Squibb

The purpose of this study is to examine the safety of Ipilimumab and patterns of use in the treatment of unresectable or metastatic melanoma in the post-approval setting

Time Perspective: this study does have a retrospective component involving a subset of patients

A Multi-National, Prospective, Observational Study in Patients With Unresectable or Metastatic Melanoma

To evaluate patterns of care, descriptive statistics will describe treatment, dosing, regimen, indication, treatment rationales, management of treatment-related adverse events, reasons for treatment termination

Descriptive statistics will be reported for healthcare utilization (inpatient, outpatient, emergency department and other ancillary services) and imputed costs

Dacarbazine

Antineoplastic Agents, Alkylating

Alkylating Agents

AZD6244

1000 mg/m2 iv infusion over at least 60 min. on day 1 of each 21 cycle

Placebo

Mark Middleton, Dr

Caroline Robert, Dr

Ian Smith, Dr

To assess the efficacy in terms of overall survival of AZD6244 in combination with dacarbazine, compared with dacarbazine alone, in first line patients with BRAF mutation positive advanced cutaneous or unknown primary melanoma

Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients

A Phase II, Double-blind, Randomised Study to Assess the Efficacy of AZD6244 in Combination With Dacarbazine Compared With Dacarbazine Alone in First Line Patients With BRAF Mutation Positive Advanced Cutaneous or Unknown Primary Melanoma

Following progression survival data was collected until documentation of death, withdrawal of consent, loss to follow-up or the final data cut-off, whichever occurred first.

PFS is the time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression). Progression is defined using RECIST (v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.

ORR rate is defined as the number (%) of subjects with at least one visit response of Complete Response (CR) or Partial Response (PR) , as defined by Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions and assessed by CT or MRI. CR, Disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions. Data obtained up until progression, or last evaluable assessment in the absence of progression, was included in the assessment of ORR

AstraZeneca

selumetinib 75mg twice daily + Dacarbazine

Selumetinib 75mg BD +Dacarbazine

Placebo BD + Dacarbazine

Total

Age, Continuous

Sex: Female, Male

Gabriella Mariani

If the true hazard ratio (HR) is 0.57, 58 deaths provides at least 80% power to demonstrate a statistically significant difference for OS, assuming a 1-sided 10% significance level.

selumetinib 75mg twice daily + dacarbazine

Selumetinib 75mg BD + Dacarbazine

Placebo + Dacarbazine

Overall Survival

Progression Free Survival

Response

Complete Response

Partial Response

Non-response

Stable Disease >=6 weeks

Progression

Objective Response Rate

Change in Target Lesion Tumour Size at Week 12

Overall Study

The treatment period consists of 3 consecutive 28 day cycles. Each cycle starts with a 4 day continuous infusion of the study medication followed by a 24 day break

APO866 is administered as 0.126 mg/m²/hr IV every 4 weeks for 4 consecutive days (96 hours) for a total of 3 cycles

APO866

Uwe Trefzer, MD PhD

This phase II study is designed to determine the efficacy and safety of APO866 for the treatment of patients with advanced cutaneous melanoma. APO866 has shown to induce growth inhibition in cultures of human melanoma cells as well as in animal models with subcutaneously implanted melanoma tumors. APO866 was considered to be safe and well tolerated in a phase I study that treated 24 patients with advanced cancer. In that study one of the two patients with advanced melanoma had a stable disease for 5 months with size reduction of some lesions. APO866 is administered by intravenous infusion continuously for 96 hours that is repeated every 4 weeks. Patients will receive 3 cycles of treatment and the primary efficacy endpoint will be assessed at Week 16. Patients will be follow-up for 12 months.

Advanced melanoma is one of the most chemo-resistant types of human cancers. The incidence increases by about 2.5% on an annual basis, with may partially be related to aging and growth of the population, as well as other environmental risk factors. Virtually no recent progress has been made in the treatment of patients with this disease. In the past 30 years, the FDA has approved only 2 agents, dacarbazine and interleukin-2, on the basis of overall response and response duration, respectively. However, these outcomes were not accompanied by a survival benefit. The most recent randomized study of Dacarbazine (DTIC) yielded an overall response rate of 7%, and to date, no other treatments, including combination therapies, have shown to improve survival when compared to DTIC alone. Hence, the mainstay of treatment for patients with advanced melanoma is DTIC-based therapy.

APO866 is a novel drug that induces cell death by specifically inhibiting the biosynthesis of Niacinamide Adenine Dinucleotide (NAD+) from niacinamide, which is essential for the cellular metabolism, protein modification and messenger synthesis. APO866 is not subject to the commonly known mechanisms of multi drug resistance (MDR). Its activity is cell cycle independent. APO866 exerted high anti-tumor activity on a broad range of different tumor cells derived from both human solid cancers and leukemias in vitro and on a large number of human xenografts in nude mice, including melanoma, and rats in vivo. Hematologic cancer cells were highly sensitive to APO866. Lymphocytes are the most sensitive normal cells to APO866 resulting in lymphocytopenia and reticulocytopenia in rats, monkeys. Furthermore, APO866 may have anti-angiogenic properties as shown in vivo.

APO866 was investigated in 24 patients with advanced cancers in a phase I study aiming to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). Treatment was well tolerated and safe. The unique DLT was thrombocytopenia. At dose levels higher than 0.036 mg/m2/hr CTC grade III lymphocytopenia, not thought to be clinically relevant, preceded all other toxicities. The recommended dose for phase II studies of APO866 is 0.126 mg/m2/hr administered by civ infusion for 4 consecutive days evry 4 weeks. This dose was selected because of its safety profile, and the translational observation that Css of APO866 at MTD was similar or higher as compared to the concentrations at which efficacy was established in vitro and in vivo. In addition, a transient decrease of serum vascular endothelial growth factor (VEGF) levels, a surrogate marker of angiogenesis, was observed within 96 hrs after the start of treatment in 9 out of 11 patients treated at MTD and the 0.144 mg/m2/hr dose level of APO866.

No objective tumor response was observed. However, 4 patients had stable disease for at least 3 months: prostate cancer (4 months), melanoma (5 months), sarcomatoid mesothelioma (3 months) and oropharyngeal cancer (5 months). In addition, lesion size reductions were observed in the melanoma patient (80% size reduction and stable size of other lesions) at an APO866 dose level of 0.072 mg/m2/hr, and in the mesothelioma patient (moderate size reductions of pleural lesions) at 0.108 mg/m2/hr.

Treatment with APO866 was safe and well tolerated. The anti-tumor effect of APO866, in particular on melanoma cells in vitro and in vivo, and its anti-angiogenic propriety support the rationale to conduct a open phase II study of APO866 in patients with advanced melanoma.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ITIL-168 in Advanced Melanoma	NCT05050006	Advanced Cutane...	ITIL-168	18 Years -	Instil Bio
A Multi-National, Prospective, Observational Study in Patients With Unresectable or Metastatic Melanoma	NCT01511913	Advanced Cutane...		18 Years -	Bristol-Myers Squibb
ITIL-168 in Advanced Melanoma	NCT05050006	Advanced Cutane...	ITIL-168	18 Years -	Instil Bio
Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients	NCT00936221	Melanoma	AZD6244 Dacarbazine Placebo	18 Years - 130 Years	AstraZeneca
A Study to Assess APO866 for the Treatment of Advanced Melanoma	NCT00432107	Melanoma	APO866	18 Years -	Valerio Therapeutics

Spots Global Cancer Trial Database for advanced cutaneous melanoma