Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Melanoma

Squamous Cell Carcinoma of Head and Neck

Carcinoma, Adenoid Cystic

Skin Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Adenocarcinoma

Adenoid Cystic Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

Dose escalation of CV8102 + anti-PD-1 therapy

Optional expansion of CV8102 + anti-PD-1 therapy

CV8102

CV8102 in combination with standard of care anti-PD-1 therapy

CV8102 + anti-PD-1 therapy

Thomas Eigentler, Prof. Dr.

This study evaluates intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma.

Patients will receive CV8102 as single agent or in combination with SoC anti-PD-1 therapy.

Open-label, cohort-based, dose escalation and expansion study

Study of Intratumoral CV8102 in cMEL, cSCC, hnSCC, and ACC

Phase I Study of Intratumoral CV8102 in Patients With Advanced Melanoma, Squamous Cell Carcinoma of the Skin, Squamous Cell Carcinoma of the Head and Neck, or Adenoid Cystic Carcinoma

* Maximum tolerated dose (MTD) and recommended dose (RD), respectively, for CV8102 alone
* MTD and recommended combination dose (RCD) for CV8102 in combination with the standard dose of an anti-PD-1 antagonist

• Tolerability and safety profile of CV8102 alone and in combination with anti-PD-1 antagonists

• Anti-tumor activity of CV8102 per irRECIST and RECIST 1.1

• Extent of tumor response at injected and non-injected lesions, if applicable

Syneos Health

Cromos Pharma LLC

CureVac

Symptoms and General Pathology

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Recurrence

Acquired Immunodeficiency Syndrome

HIV Infections

Anti-Infective Agents

All Drugs and Chemicals

HIV Protease Inhibitors

Protease Inhibitors

Nelfinavir

Enzyme Inhibitors

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

1250 mg Nelfinavir twice daily Monday-Sunday

1250 mg Nelfinavir twice daily Monday - Sunday

John M. Buatti, M.D.

The purpose of this study is to evaluate the FDA-approved drug nelfinavir (NFV) as an oncologic agent for adenoid cystic cancers of the head and neck.

Specifically, subjects will be asked to take 1250 mg twice daily and follow-up with their medical oncologist as clinically indicated while taking this medication.

Subjects would be evaluated for quality of life issues utilizing the EORTC QLQ-C30 2-page questionnaire.

Subjects would also be evaluated clinically by the oncologist to determine if the NFV was having an anti-neoplastic effect.

The study remains unfunded. Therefore, potential subjects must be willing to provide self-travel to study site. This study requires a screening visit, initial study visit, and monthly follow-up. Subjects are not reimbursed for time, travel, or physician costs.

The hypothesis of this study is that nelfinavir, by inhibiting the Akt and MAPK pathways, can inhibit adenoid cystic carcinoid growth. These cancers are heavily dependent on these signalling pathways.

Adenoid cystic carcinomas (ACC) are rare and account for about 1% of all head and neck cancers. They stem from salivary glands and are known for their tendency to spread along nerve sheaths (perineural spread). ACC is known for its prolonged clinical course, multiple recurrence and the delayed onset of distant metastases. The median/mean age at presentation is 47-56. Although 5 year disease free survivals (DFS) are 65-70%, the 15 year DFS drops to 30-40%. If followed long enough, 35% of patients will eventually develop metastatic disease.

The most common treatment of ACC is surgery followed by post-operative radiotherapy. When ACC recurs, management options are often limited both by the morbidity and low efficacy of re-irradiation and repeated surgical resection. Reported response rates to chemotherapy are low and when it occurs, the duration of the response is short lived.

In an effort to explore possible targeted therapies for patients with recurrent ACC, Dr. Gupta's lab examined the activation of 3 signaling proteins (EGFR, Akt, and MAPK) in 9 different paraffinized tissue blocks. Initial indications from in vitro studies demonstrates NFV is tumoricidal at clinically achievable concentrations. To explore the clinical benefit of this FDA-approved medication, we seek to implement its off label use in patients who have failed all other therapies and have no other therapeutic options left.

Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck

A Phase II Trial of the HIV Protease Inhibitor Nelfinavir in Patients With Recurrent Symptomatic Adenoid Cystic Cancers of the Head and Neck

Tumor progression as defined by RECIST version v1.1 criteria with ordinal measurements of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).

Holden Comprehensive Cancer Center

University of Iowa

Professor & Chair of Radiation Oncology

1250 mg Nelfinavir twice daily Monday-Sunday

Nelfinavir: 1250 mg Nelfinavir twice daily Monday - Sunday

Age, in years, of study participants at consent

Age, Customized

Self-reported gender at time of study enrollment

Sex/Gender, Customized

United States

Region of Enrollment

Favorable selection criteria were used in study design. RECIST assessed at a median interval of 12 weeks - this difference in methods may have artificially prolonged the progression free survival observed in this study.

John M. Buatti, M.D., Chair, Department of Radiation Oncology

Those with adverse events necessitating interruption of intervention and removal from study were not assessed for outcome measures

Tumor Progression

Overall Study

Antineoplastic Agents

Amino Acids

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Imatinib

Sandrine Faivre, MD

Caroline Robert, MD

This is a Phase II study of imatinib (Glivec) administered as a daily oral treatment in patients with recurrent/metastatic adenoid cystic carcinoma of the head and neck overexpressing KIT.

Patients with relapsing and/or metastatic adenoid cystic carcinoma of the salivary gland of the head and neck are usually poor responders to conventional cytotoxic chemotherapy.

The investigation of proliferation pathways involving tyrosine kinase receptors such as c-kit receptor (KIT) and PDGF receptor may allow to identify a molecular target for novel therapeutic approaches in patients with adenoid cystic carcinoma who failed locoregional treatment.

Several publications in the literature and the pathological study we conducted in Institut Gustave Roussy show that KIT overexpression is observed in at least 80-90% of the cases of adenoid cystic carcinoma, supporting the investigation of imatinib in patients with adenoid cystic carcinoma overexpressing KIT.

Imatinib is an orally administrated, well tolerated compound that could be given on an outpatient schedule to patients with relapsing/metastatic adenoid cystic carcinoma of the head and neck.

Because of the infrequent occurrence of salivary gland malignancies, a multicenter trial will be mandatory and the study will include at least 2 centers represented by Institut Gustave Roussy, Villejuif; and Hôpital Georges-Pompidou, Paris.

Study of Imatinib (Glivec) in Patients With Adenoid Cystic Carcinoma of the Head and Neck

Phase II Study of Imatinib (Glivec) Administered as a Daily Oral Treatment in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma of the Head and Neck Overexpressing KIT

Gustave Roussy, Cancer Campus, Grand Paris

Mitogens

epidermal growth factor receptor tyrosine kinase inhibitors

EGFR-TK Inhibitor

Youxin Ji, MD

There is no clinical study on epidermal growth factor receptor tyrosine kinase inhibitors has been systematically conducted in adenoid cystic carcinoma.

This is a phase II study EGFR TKIs in adenoid cystic carcinoma to evaluate its efficacy in this disease.

The histologic appearance of adenoid cystic carcinoma is low grade, management of this malignancy is a challenge because of its insidious local growth pattern and lack of effency with chemotherapy or radiotherapy in metastatic disease.

In other performed clinical trials, objective responses to any cytotoxic agent or regimen are infrequent, whereas stabilization of disease was observed more commonly.

In adenoid cystic carcinoma, the study focusing on EGFR pathway is rare. According to previous study, adenoid cystic carcinoma cell lines have increased pAkt activity when EGF-stimulation is added. And when treated with EGFR/VEGFR TK dual inhibitor, the phosphorylated form of Akt decreased despite of total level of Akt is remained unchanged.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Intratumoral CV8102 in cMEL, cSCC, hnSCC, and ACC	NCT03291002	Melanoma (Skin) Squamous Cell C... Carcinoma, Squa... Carcinoma, Aden...	CV8102 CV8102 + anti-P...	18 Years -	CureVac
Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck	NCT01065844	Carcinoma, Aden... Head and Neck N...	Nelfinavir	18 Years -	University of Iowa
Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck	NCT01065844	Carcinoma, Aden... Head and Neck N...	Nelfinavir	18 Years -	University of Iowa
Study of Imatinib (Glivec) in Patients With Adenoid Cystic Carcinoma of the Head and Neck	NCT00180921	Cancer of the H... Carcinoma, Aden...	Imatinib	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris
Tyrosine Kinase Inhibitors in Metastastic Adenoid Cystic Carcinoma	NCT04974866	Carcinoma, Aden...	EGFR-TK Inhibit...	18 Years - 90 Years	Qingdao Central Hospital

Spots Global Cancer Trial Database for carcinoma, adenoid cystic