Trial Title:
Agnostic Therapy in Rare Solid Tumors
NCT ID:
NCT06638931
Condition:
Urachal Cancer
Parathyroid Carcinoma
Fibrolamellar Carcinoma
Angiosarcoma
Secretory Carcinoma of Breast
Anal Neoplasms
Metaplastic Breast Carcinoma
Translocation Renal Cell Carcinoma
Carcinosarcoma
Small Intestine Neoplasms
Cholangiocarcinoma
Sertoli-Leydig Cell Tumor
Adenoid Cystic Carcinoma
Mesothelioma
Neuroblastoma
Adrenal Gland Neoplasms
Penile Neoplasms
Apocrine Carcinoma
Fibrosarcoma
Cancer of Unknown Primary
Hemangioblastoma
Thyroid Neoplasms
Hepatoblastoma
Fallopian Tube Neoplasms
Leiomyosarcoma
Vaginal Neoplasms
Neurofibrosarcoma
Gallbladder Neoplasms
Osteosarcoma
Biliary Tract Neoplasms
Clear Cell Endometrial Cancer
Yolk Sac Tumor
Vulvar Neoplasms
Kaposi Sarcoma
Ovarian Epithelial Cancer
Soft Tissue Sarcoma
Urethral Neoplasms
Granulosa Cell Tumor
Primitive Neuroectodermal Tumor
Neuroendocrine Tumors
Trophoblastic Tumor
Conditions: Official terms:
Sarcoma, Kaposi
Carcinoma
Neoplasms
Sarcoma
Endometrial Neoplasms
Neuroblastoma
Cholangiocarcinoma
Neuroendocrine Tumors
Mesothelioma
Mesothelioma, Malignant
Breast Neoplasms
Carcinoma, Ovarian Epithelial
Osteosarcoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Leiomyosarcoma
Carcinoma, Adenoid Cystic
Endodermal Sinus Tumor
Carcinosarcoma
Mixed Tumor, Mullerian
Hemangiosarcoma
Hepatoblastoma
Thyroid Neoplasms
Trophoblastic Neoplasms
Fibrosarcoma
Biliary Tract Neoplasms
Fallopian Tube Neoplasms
Neurofibrosarcoma
Hemangioblastoma
Vulvar Neoplasms
Parathyroid Neoplasms
Granulosa Cell Tumor
Gallbladder Neoplasms
Leydig Cell Tumor
Vaginal Neoplasms
Adrenal Gland Neoplasms
Penile Neoplasms
Sertoli-Leydig Cell Tumor
Urethral Neoplasms
Anus Neoplasms
Intestinal Neoplasms
Nivolumab
Conditions: Keywords:
Urachal Adenocarcinoma
Parathyroid Carcinoma
Nasopharyngeal Epithelial Tumors
Fibrolamellar Carcinoma
Angiosarcoma
Secretory Breast Carcinoma
Anal Cancer
Metaplastic Breast Carcinoma
Chromophobe Renal Carcinoma
Carcinosarcoma
Small Intestine Cancer
Cholangiocarcinoma
Sertoli-Leydig Cell Tumors
Non-Squamous Cervical Neoplasm
Tracheal Epithelial Tumors
Non-Adenoid Cystic Salivary Tumors
Mesothelioma
Neuroblastoma
Adrenal Neoplasm
Penile Cancer
Apocrine Carcinoma
Fibrosarcoma
Cancer of Unknown Primary
Hemangioblastoma
Thyroid Cancer
Hepatoblastoma
Fallopian Tube Cancer
Leiomyosarcoma
Vaginal Cancer
Neurofibrosarcoma
Gallbladder Cancer
Osteosarcoma
Biliary Tract Cancer
Clear Cell Endometrial Cancer
Yolk Sac Tumor
Non-Squamous Bladder Cancer
Vulvar Cancer
Kaposi Sarcoma
Ovarian Epithelial Cancer
Soft Tissue Sarcoma
Urethral Cancer
Granulosa Cell Tumor
Adenoid Cystic Carcinoma
Primitive Neuroectodermal Tumor
Neuroendocrine Tumors
Trophoblastic Tumor
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
The study aims to evaluate the efficacy of the anti-PD1 monoclonal antibody, nivolumab,
in the treatment of patients with advanced or metastatic rare malignant neoplasms. This
study will be conducted as a single-arm trial, including patients who have a Combined
Positive Score (CPS) of 10 or greater and who have demonstrated progression on standard
treatment. Participants will be monitored to determine their response to treatment and
any adverse effects associated with the use of nivolumab. The expectation is to provide
evidence regarding the efficacy of this immunotherapeutic agent in a difficult-to-treat
population, contributing to the advancement of therapeutic options available for these
patients.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
The intervention consists of administering Nivolumab 480 mg intravenously every 4 weeks,
with a +5 day window for postponement but not for advancement of treatment. Treatment
will continue until limiting toxicity, disease progression, or for a maximum period of 12
months (13 cycles) as maintenance therapy, provided the patient maintains stable disease,
a partial response, or a complete response. Patients who are off treatment for more than
56 days (2 cycles) due to Nivolumab-related toxicities or other clinical issues will be
discontinued from the protocol.
After 12 months of treatment or in the event of study discontinuation for any reason,
patients will be followed by the research team via telephone every 60 days, with a +/- 7
day window, until death.
Arm group label:
Single-Arm Efficacy Study
Summary:
The ANTARES study is a phase II basket trial designed to evaluate the tissue-agnostic
efficacy of the monoclonal anti-PD1 antibody, nivolumab, in patients with advanced or
metastatic rare tumors.
The study aims to treat rare malignancies with PD-L1 expression (CPS ≥ 10), regardless of
the tumor's tissue type or location. Patients who have not responded to standard
treatments will be included, and treatment will last for up to 12 months. The study will
assess objective response, progression-free survival, and biomarkers such as PD-L1,
ctDNA, and microvesicles, in a multicenter collaborative effort to provide innovative
therapeutic options for this underrepresented population
Detailed description:
The ANTARES study is a phase II "basket" trial designed to evaluate the tissue-agnostic
efficacy of the monoclonal anti-PD1 antibody, nivolumab, in patients with advanced or
metastatic rare tumors. A "basket" trial is an innovative type of clinical trial where
patients with different types of cancers, but sharing a common molecular feature (in this
case, PD-L1 expression), are treated with the same therapy, regardless of the tumor's
site of origin. This approach allows for the evaluation of treatments targeting specific
molecular characteristics, independent of the primary cancer type.
Rare tumors, as defined by the World Health Organization (WHO), have an incidence of
fewer than six cases per 100,000 people per year. Although each rare cancer type is
individually uncommon, collectively they account for 25-30% of all malignancies and are
often underrepresented in clinical trials due to recruitment challenges and limited
funding. As a result, patients with rare cancers generally have a poorer prognosis
compared to those with more common tumors.
In this study, patients with advanced or refractory rare malignancies expressing PD-L1,
with a combined positive score (CPS) of ≥10, will be treated with nivolumab. Treatment
will be administered until disease progression or for a maximum duration of 12 months,
aiming to assess the efficacy and safety of this tissue-agnostic immunotherapy approach.
Efficacy will be measured according to RECIST v1.1 criteria, with objective response as
the primary endpoint. Additionally, the study will assess response biomarkers, including
PD-L1, circulating tumor DNA (ctDNA), and microvesicles, to better understand the
correlation between biomarker expression and clinical outcomes.
This multicenter trial, with an estimated duration of four years, will be conducted at
Institute of Cancer of the State of São Paulo (ICESP) and other partner institutions. The
study aims to overcome existing barriers in rare cancer treatment by offering an
innovative approach that explores the potential of personalized therapies based on
molecular characteristics, rather than the tumor's primary site
Criteria for eligibility:
Criteria:
Inclusion Criteria
1. Age 18 years or older.
2. Patients with immunohistochemistry for PD-L1 with a combined positive score (CPS) of
10 or higher.
3. Patients with progression or intolerance to already approved and accessible
treatments for the specific neoplasm and population.
4. Documented disease progression radiologically after the last routine treatment.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Measurable lesion per RECIST v1.1. Lesions previously treated with radiotherapy can
only be used as target lesions if they are confirmed to be progressing by imaging
before enrollment.
7. Male participants must meet at least one of the following conditions:
1. Considered infertile;
2. No fertile partner;
3. Has a fertile partner who agrees to follow contraceptive guidance throughout
the study period and for at least 6 months after the last dose of Nivolumab;
and
4. Agrees to abstain from sperm donation throughout the study period and for at
least 6 months after the last dose of Nivolumab.
8. Female participants must meet at least one of the following conditions:
1. Considered infertile;
2. Agrees to follow contraceptive guidance throughout the study period and for at
least 6 months after the last dose of Nivolumab;
9. Estimated life expectancy greater than 12 weeks, as determined by the investigator
or delegated sub-investigator.
10. Preserved organ functions defined by:
- Absolute neutrophil count ≥ 1,000;
- Hemoglobin ≥ 8.0 g/dL (patients may receive transfusions to reach this level);
- Platelet count ≥ 100,000;
- Total bilirubin ≤ 1.5 × Upper Limit of Normal (ULN), or ≤ 3.0 × ULN for
patients with Gilbert's syndrome;
- Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN
(≤ 5 × ULN in the presence of liver metastases);
- Creatinine clearance > 30 mL/min (estimated by Cockcroft-Gault).
11. Diagnosis of rare cancer (List I) confirmed by histopathological examination, with
the possibility of including other types of rare tumors (incidence of less than 6 in
every 100,000) after careful evaluation and approval by the study board.
- List I:
- Urachal adenocarcinoma
- Parathyroid carcinoma
- Nasopharyngeal epithelial tumors
- Fibrolamellar carcinoma of any primary site
- Angiosarcoma of any primary site
- Secretory breast carcinoma
- Anal cancer
- Metaplastic breast carcinoma
- Chromophobe renal carcinoma, Microphthalmia-associated Transcription
Factor (MiT) family translocation renal carcinoma; renal carcinoma with
Fumarate Hydratase (FH) or Succinate Dehydrogenase (SDH) deficiency
- Carcinosarcoma of any primary site
- Small intestine cancer
- Cholangiocarcinoma
- Sertoli-Leydig cell tumors
- Cervical cancer of non-epidermoid histology
- Tracheal epithelial tumors
- Non-cystadenoma salivary gland tumors
- Mesothelioma of any site
- Neuroblastoma
- Adrenal cancer
- Penile cancer
- Apocrine carcinoma
- Fibrosarcoma of any primary site
- Cancer of unknown primary site
- Hemangioblastoma of any primary site
- Thyroid cancer
- Hepatoblastoma
- Fallopian tube cancer
- Leiomyosarcoma of any primary site
- Vaginal cancer
- Neurofibrosarcoma of any primary site
- Gallbladder cancer
- Osteosarcoma of any primary site
- Bile duct cancer
- Clear cell endometrial carcinoma
- Yolk sac tumor of any primary site
- Non-epidermoid bladder cancer
- Vulvar cancer
- Kaposi's sarcoma
- Epithelial ovarian cancer
- Soft tissue sarcoma
- Urethral cancer
- Granulosa cell tumor of any primary site
- Cystadenoma carcinoma
- Primitive neuroectodermal tumor of any primary site
- Pure or mixed neuroendocrine tumors with neuroendocrine component
- Trophoblastic tumor
Exclusion Criteria
1. Previous treatment lines with immunotherapy (immune checkpoint inhibitors).
2. Pregnant or breastfeeding individuals.
3. Limiting comorbidity, in the opinion of the investigator.
4. Active infection.
5. Major surgery within the last 4 weeks.
6. Functional class II or greater heart failure.
7. Myocardial infarction or stroke within the last 6 months.
8. History of pulmonary fibrosis or pneumonitis.
9. Autoimmune diseases, except for patients with vitiligo and/or controlled
thyroid/hypothyroidism without the use of immunosuppressors.
10. Second invasive primary tumor diagnosed in the last 3 years and/or with active
disease, except for localized skin tumors (non-melanoma) that have been treated with
curative intent.
11. Patients with prolonged QT interval.
12. Uncontrolled Central Nervous System (CNS) metastases. Patients who have previously
received local treatment, such as radiotherapy, will be eligible if clinical and
radiological stability is demonstrated in the 2 weeks prior to the start of
treatment. Patients must not be using corticosteroids for managing CNS disease.
13. Presence of meningeal carcinomatosis.
14. Worsening renal and liver function in the 14 days prior to enrollment.
15. History of solid organ transplantation with or without immunosuppression.
16. Patients with untreated acquired immunodeficiency. Immunocompromised patients may be
included as long as they do not have active opportunistic disease and/or active
infection, after thorough clinical evaluation by the investigator or
sub-investigator. HIV-positive patients must have documented undetectable viral load
prior to inclusion.
17. Chronic use of corticosteroids at doses greater than 10 mg/day of prednisone or
equivalent. Patients with adrenal insufficiency of non-autoimmune etiology (e.g.,
previous bilateral adrenalectomy) may be included if they are clinically compensated
with 10 mg/day of prednisone or equivalent or less.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital São Rafael
Address:
City:
Salvador
Zip:
41253-190
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Lívia QS Andrade, Doctor
Phone:
+55 71 3409-8000
Email:
livia.andrade@oncologiador.com.br
Contact backup:
Last name:
Research Center, Assistant
Phone:
+55 11 2109-8800
Email:
regulatorio.idor@rededor.com.br
Facility:
Name:
Hospital São Carlos
Address:
City:
Fortaleza
Zip:
60170-170
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Karine M Trindade
Phone:
+55 85 3257-9408
Email:
regulatorio.idor@rededor.com.br
Contact backup:
Last name:
Research Center
Phone:
55 11 2109-8800
Email:
regulatorio.idor@rededor.com.br
Facility:
Name:
Hospital Santa Cruz
Address:
City:
Curitiba
Zip:
80420-090
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Guilherme LS Pereira, Doctor
Phone:
+55 41 3312-3000
Email:
guilherme.stelko@hospitalsantacruz.com
Contact backup:
Last name:
Research Center, Assistant
Phone:
+55 11 2109-8800
Email:
regulatorio.idor@rededor.com.br
Facility:
Name:
IDOR Recife
Address:
City:
Recife
Zip:
52010-010
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Rafael CA Lima, Doctor
Phone:
+55 81 3131-7800
Email:
cep@idor.org
Contact backup:
Last name:
Research Center, Assistant
Phone:
55 11 2109-8800
Email:
regulatorio.idor@rededor.com.br
Facility:
Name:
Instituto D'or de Pesquisa e Ensino
Address:
City:
Sao Paulo
Zip:
04.501-000
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Renata RC Bonadio, Doctor
Phone:
+55 11 2109-8800
Email:
renata.bonadio@idor.org
Contact backup:
Last name:
Research Center, Assistant
Phone:
+55 11 2109-8800
Email:
regulatorio.idor@rededor.com.br
Facility:
Name:
Instituto do Câncer do Estado de São Paulo - ICESP
Address:
City:
São Paulo
Zip:
05403-010
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Camila MV Moniz, Doctor
Phone:
+55 11 3893-3925
Email:
camila.venchiarutti@hc.fm.usp.br
Contact backup:
Last name:
Research Center, Assistant
Phone:
+55 11 3893-3566
Email:
icesp.pesqclinica@hc.fm.usp.br
Investigator:
Last name:
Camila MV Moniz, Doctor
Email:
Principal Investigator
Investigator:
Last name:
Raelson Miranda, Doctor
Email:
Sub-Investigator
Investigator:
Last name:
Renata RC Bonádio, Doctor
Email:
Sub-Investigator
Facility:
Name:
DF Star
Address:
City:
Brasília
Zip:
70390-903
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Lucila SS Rocha, Doctor
Phone:
+55 61 3251-3100
Email:
lucila.srocha@dfstar.com.br
Contact backup:
Last name:
Research Center, Assistant
Phone:
+55 11 2109-8800
Email:
regulatorio.idor@rededor.com.br
Facility:
Name:
Instituto D'Or de Pesquisa e Ensino
Address:
City:
Rio De Janeiro
Zip:
22281-100
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Clarissa SR Baldotto, Doctor
Phone:
+55 21 3883-6000
Email:
contato@idor.com.br
Contact backup:
Last name:
Research Center, Assistant
Phone:
+55 11 2109 8800
Email:
regulatorio.idor@rededor.com.br
Start date:
July 1, 2024
Completion date:
May 2028
Lead sponsor:
Agency:
Instituto do Cancer do Estado de São Paulo
Agency class:
Other
Collaborator:
Agency:
Financiadora de Estudos e Projetos
Agency class:
Other
Source:
Instituto do Cancer do Estado de São Paulo
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06638931
