Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Substance Related Disorders

Rare Diseases

Melanoma

Drug-Related Side Effects and Adverse Reactions

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

Chemically-Induced Disorders

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Early discontinuation of nivolumab maintenance therapy in patients with irresectable stage III or metastatic melanoma

nivolumab

Astrid A.M. van der Veldt, Dr.

Safe Stop IPI-NIVO Trial: Early discontinuation of nivolumab upon achieving a (confirmed) complete or partial response in patients with irresectable stage III or metastatic melanoma treated with first-line ipilimumab-nivolumab

Safe Stop Ipilimumab-nivolumab (IPI-NIVO) Trial

Safe Stop IPI-NIVO Trial: Early Discontinuation of Nivolumab Upon Achieving a (Confirmed) Complete or Partial Response in Patients With Irresectable Stage III or Metastatic Melanoma Treated With First-line Ipilimumab-nivolumab

The rate of ongoing response at 12 months in patients with irresectable stage III or metastatic melanoma who are treated with first-line ipilimumab-nivolumab and who early discontinue nivolumab upon achieving a CR or PR according to RECIST v1.1

Ongoing response at 24 months after start of first-line treatment with ipilimumab-nivolumab

Disease control (CR/PR) at different time points

Duration of response (CR/PR) measured until progressive/recurrent disease

Melanoma specific survival measured from start of first-line treatment with ipilimumab-nivolumab until melanoma related death

Overall survival (OS) measured from start of first-line treatment with ipilimumab-nivolumab until death by any cause

Impact of discontinuation treatment on (S)AEs

Overall Response Rate (ORR) per RECIST v1.1 in retreated patients

Disease control (CR/PR/SD \[stable disease\]/not PD \[progressive disease\]) after restarting (systemic) treatment for melanoma

Quality of life is measured using questionnaires: EuroQoL EQ-5D-5

Erasmus Medical Center

Doctor

Chondrosarcoma

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Soft Tissue Sarcoma

Apatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Apatinib orally 500mg once daily half an hour after meal

Apatinib Mesylate

Anti-angiogenesis Tyrosine kinase inhibitors (TKIs) have been proved to show promising effects on prolonging progression-free survival (PFS) for advanced chondrosarcoma after failure of standard multimodal Therapy. Methylsulfonic apatinib is one of those TKIs which specifically inhibits VEGFR-2. This study summarizes the experience of two Peking University affiliated hospitals in off-label use of apatinib in the treatment of extensively pre-treated chondrosarcoma.

Apatinib for Inoperable Advanced Chondrosarcoma

The Effectivity and Toxicity of Apatinib for Unresectable Advanced Chondrosarcoma: a Multicentric Retrospective Study

from initial treatment to date of recorded progression or death or last follow-up

from initial treatment to death or last follow-up

Peking University People's Hospital

Osteosarcoma

Neoplasms, Bone Tissue

Etoposide

Ifosfamide

Etoposide phosphate

Isophosphamide mustard

Apatinib: 500 mg QD po (BSA ≥ 1.0) or 250 mg QD po (BSA \< 1.0); IE: ifosfamide 1.8 g/m2/d d1-3; etoposide 100 mg/m2/d d1-3 Q2w

apatinib

Wei Guo, M.D.

Apatinib has led to positive responses in the treatment of osteosarcoma refractory to first-line chemotherapy. However, apatinib demonstrates only short-lived activity, and the disease control of musculoskeletal lesions is worse than that of pulmonary lesions. This treatment failure has been partly overcome by the addition of ifosfamide and etoposide (IE). We have ever retrospectively compared the activity of apatinib + IE in relapsed or refractory osteosarcoma in two sarcoma centers in China and concluded that for osteosarcoma with multiple sites of metastasis, apatinib + IE demonstrated clinically meaningful antitumor activity and delayed disease progression in patients with recurrent or refractory osteosarcoma after failure of chemotherapy. However to overcome the influence of other interventions on the outcome, we are currently performing a prospective trial to investigate this combination, from which more accurate data on this treatment strategy are expected.

Apatinib Plus IE Chemotherapy (Ifosfamide and Etoposide) for Relapsed or Refractory Osteosarcoma

Apatinib in Combination With Ifosfamide and Etoposide (IE) for Relapsed or Refractory Osteosarcoma Progressed Upon First-line Chemotherapy (AIEO): a Prospective, Multiple-centre, Single-arm, Phase 2 Trial

from the start of target treatment until disease progression or death, whichever came first.

from the date of treatment initiation to death from any cause.

Peking University Shougang Hospital

Musculoskeletal Tumor Center

Digestive System Diseases

Carcinoma

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms, Squamous Cell

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Nimotuzumab

Neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab

neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery

Dong Qian, M.D.

Xiao-Yang Li

Xiaoyang Li, M.D.

Neoadjuvant chemoradiotherapy followed by surgery has been the standard modality for locally advance esophageal carcinoma. According to CROSS study, the pathological complete remission rate achieved by paclitaxel and carboplatin with 41.4 Gy/23f was 49% for esophageal squamous cell carcinoma. But the 10-year overall survival rate was only 38%. How to increase the overall survival of esophageal carcinoma is a pivotal task. Both of Camrelizumab and Nimotuzumab have been demonstrated to be efficacious in the neoadjuvant treatment for esophageal squamous cell carcinoma in some small sample-size trials. Therefore, this trial is designed to combine adjuvant chemoradiotherapy with Camrelizumab and Nimotuzumab for resectable \& potentially resectable locally advanced esophageal squamous cell carcinoma and explore the safety and primary efficacy of such combination.

Trial Title Neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab for resectable \& potentially resectable locally advanced esophageal squamous cell carcinoma: A phase I/II study (NCRCN) Trial Objective To explore the safety and primary efficacy of neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab for resectable \& potentially resectable locally advanced esophageal squamous cell carcinoma.

Trial Design: To enroll 57 patients with resectable \& potentially resectable locally advanced esophageal squamous cell carcinoma to receive neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery.

Staging Examination before Adjuvant Treatment: a. ECOG scoring. b. PET-CT, Upper GI endoscopy \& endoscopic ultrasound and barium swallow (preferred), or chest contrast CT, abdominal ultrasonography, bone scan, Upper GI endoscopy \& endoscopic ultrasound and barium swallow. c. Bronchoscopy for patients with suspicious invasion into trachea or bronchus. d. Pulmonary function test.

Adjuvant chemoradiotherapy Radiotherapy CT Simulation: CT with intravenous contrast is recommended for simulation. Scan thickness should be less than 5 mm from lower margin of mandibular to lower margin of L2. Thermal mask is recommended.

Delineation of Targets: Involved field irradiation is the general principle. Gross Tumor Volume (GTV) is the primary esophageal tumor and the metastatic lymph node. The Clinical Target Volume (CTV) provided a proximal and distal margin of 3 cm and a 0.8 cm radial margin around the primary esophageal tumor and a proximal and distal margin of 1 cm and a 0.8 cm radial margin around the metastatic lymph nodes. The Planning Target Volume (PTV) was defined as an 8-mm margin of the CTV for tumor motion and set-up variations.

Prescription Dose: 41.4 Gy/23f to PTV. Dosimetric Limitation of Organ at Risk: 95% prescription dose should cover 100% PTV and 95% PTV should receive 100% prescription dose. Total Lung: V20\<25%, Dmean\<13Gy, V5\<50%. Spinal Cord: Dmax\<45Gy. Heart: V30\<40%, Dmean\<25Gy.

Treatment Implementation: Radiotherapy is implemented every day. Cone-beam CT should utilized every week to minimize set-up error.

Chemotherapy Paclitaxel 50mg/m2+Carboplatin AUC=2 qw×5c, Nimotuzumab 200mg qw×5c, Camrelizumab 200mg q4w×2c.

Restaging Examination before Surgery: a. ECOG scoring. b. PET-CT and barium swallow (preferred), or chest contrast CT, abdominal ultrasonography, bone scan and barium swallow. c. Pulmonary function test.

Restaging is aiming to exclude patients with disease progression after adjuvant treatment.

Surgery Surgery is scheduled for 4 to 6 weeks after completion of adjuvant treatment. McKeown or Ivor-Lewis esophagectomy, including two-field lymphadenectomy with total mediastinal lymph node dissection, is performed. The dissection of left and right recurrent laryngeal nerve nodes is mandatory.

Follow-up: Patients should be follow-up every three months right after the completion of surgery to 3 years after surgery. Then follow-up every half year is allowed to 5 years after surgery. After 5 years, follow-up every year is appropriate. In follow-up, chest contrast CT and abdominal ultrasonography should be implemented. Endoscopy should be undertaken every year for all patients.

Primary Endpoint: Pathological complete remission rate and major pathological remission rate (CAP Cancer Protocol for Esophageal Carcinoma).

Secondary Endpoint: Rate of adverse events (CTCAE V4.0), Complete resection rate, 1-, 2-, 3-year Disease-free survival rate (DFS).

To enroll 57 patients with resectable \& potentially resectable locally advanced esophageal squamous cell carcinoma to receive neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery.

Neoadjuvant Chemoradiotherapy Combined With Camrelizumab and Nimotuzumab for Esophageal Squamous Cell Carcinoma

Neoadjuvant Chemoradiotherapy Combined With Camrelizumab and Nimotuzumab for Resectable & Potentially Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase I/II Study (NCRCN)

Pathological complete remission rate (CAP Cancer Protocol for Esophageal Carcinoma)

Major pathological remission rate (CAP Cancer Protocol for Esophageal Carcinoma)

1-, 2-, 3-year Disease-free survival rate (DFS).

Anhui Provincial Hospital

Professor

Symptoms and General Pathology

Neoplasm Metastasis

Mechlorethamine

Antineoplastic Agents, Alkylating

Alkylating Agents

apatinib orally daily and ifosfamide 1.8mg/m2/d d1-3, etoposide 100mg/m2/d d1-3

ifosfamide and etoposide

Today, using a multi-modal approach consisting of preoperative (neoadjuvant) systemic polychemotherapy followed by local surgical therapy and then postoperative (adjuvant) chemotherapy, long-term, disease-free survival can be achieved in 60- 70% of osteosarcoma patients. However treatment options for osteosarcomas, especially in the setting of metastatic or unresectable disease, are very scarce. Apatinib has been proved to be an effective agent to prolong progression-free survival in advanced osteosarcoma. But after 4-6 months' treatment, secondary resistance always occurred with musculoskeletal lesions' progression or new metastasis.

Nowadays giving therapeutic doses of IE concurrently with anti-angiogenesis tyrosine kinase inhibitors is a conceptually attractive strategy for treating patients with refractory osteosarcoma according to prospective trial of lenvatinib +IE reported by Gaspar et al at 2019 ESMO and 2020 ESMO. Thus This study was designed to review our experience in real world for off-label use and characterize the toxicity profile of concurrent apatinib+IE and IE alone in patients with relapsed or refractory osteosarcoma.

Apatinib + Ifosfamide and Etoposide for Relapsed or Refractory Osteosarcoma

Apatinib+Ifosfamide and Etoposide (IE) Versus IE Alone for Relapsed or Refractory Osteosarcoma: a Real-world Study in Two Centers in China

from start treatment to progression/death

Micronutrients

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Amino Acids

Antibodies

Doxorubicin

Liposomal doxorubicin

Leucovorin

Methotrexate

Cisplatin

Immunoglobulins

Tyrosine Kinase Inhibitors

Tyrosine

AP = Doxorubicin (Adriamycin) 20 mg/m2/day \* 2 day (total/cycle 40 mg/m²)

+ Cisplatin 100 mg/m2/course (total/cycle 120 mg/m²);

I = Ifosfamide 2000 mg/m2/day \*5 day (total/cycle 10000 mg/m²);

apatinib = 500 mg QD;

AP = Doxorubicin (Adriamycin) 37.5 mg/m2/day \* 2day (total/cycle 75 mg/m²)

+ Cisplatin 120 mg/m2/course (total/cycle 120 mg/m²);

M = Methotrexate 12000 mg/m2 (total/cycle 12000 mg/m²) with leucovorin rescue;

I = Ifosfamide 2400 mg/m2/day \*5day (total/cycle 12000 mg/m²);

camralizumab = 200mg ivgtt. Q2W;

AP = Doxorubicin (Adriamycin) 37.5 mg/m2/day \* 2day (total/cycle 75 mg/m²)

+ Cisplatin 120 mg/m2/course (total/cycle 120 mg/m²);

M = Methotrexate 12000 mg/m2 (total/cycle 12000 mg/m²) with leucovorin rescue;

I = Ifosfamide 2400 mg/m2/day \*5day (total/cycle 12000 mg/m²);

AP = Doxorubicin (Adriamycin) 37.5 mg/m2/day \* 2day (total/cycle 75 mg/m²)

+ Cisplatin 120 mg/m2/course (total/cycle 120 mg/m²) ; M = Methotrexate 12000 mg/m2 (total/cycle 12000 mg/m²) with leucovorin rescue; I = Ifosfamide 2400 mg/m2/day \*5day (total/cycle 12000 mg/m²)

MAPI chemotherapy

anti-angiogenesis tyrosine kinase inhibitors 500 mg orally daily

Camrelizumab

Lu Xie, M.D.

Xin Sun, M.D.

Wei Guo, M.D. and Ph.D.

Treatment strategies for high-grade osteosarcoma with multidrug chemotherapy and resection result in 3-year event-free survival of 60-70%. The most common factors predicting survival are presence of metastases, histological response to preoperative chemotherapy and complete surgical resection. Four of the active drugs in osteosarcoma include cisplatin, doxorubicin, high-dose methotrexate and ifosfamide and this combination (MAPI), given preoperatively and postoperatively, is widely used for the treatment of osteosarcoma in China. Apatinib also has activity in advanced setting and when incorporated into the treatment of patients with metastatic disease seemed to improve progression-free survival. Combination of apatinib and camrelizumab resulted in durable therapuetic effect in selected cases. Though EURAMOUS-1 suggested that changing chemotherapy postoperatively on the basis of histological response did not improve outcomes. The exploratory study with radomised design to compare combination of chemotherapy with target drug or combination of chemotherapy with anti-PD-1 antibody versus standard chemotherapy has not been tried yet. Thus we aim to investigate the efficacy and toxicity of these combiantions versus standard chemotherapy in this study.

Comparison of MAPI+Camrelizumab Versus API+Apatinib Versus MAPI in Patients With a Poor Response to Preoperative Chemotherapy for Newly Diagnosed High-grade Osteosarcoma

A Randomized Trial of Comparison of MAPI+Camrelizumbab Verus API+Apatinib Versus MAPI in Patients With a Poor Response to Preoperative Chemotherapy for Newly Diagnosed High-grade Osteosarcomaies : an Open-label, Exploratory Study

from initial treatment after definitive surgery to progression/death/ last follow up

from initial treatment after definitive surgery to death/ last follow up

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safe Stop Ipilimumab-nivolumab (IPI-NIVO) Trial	NCT05652673	Melanoma Stage ... Melanoma Stage ... Immunotherapy Toxicity, Drug	nivolumab	18 Years -	Erasmus Medical Center
Apatinib for Inoperable Advanced Chondrosarcoma	NCT04260113	Efficacy Toxicity, Drug	Apatinib Mesyla...	-	Peking University People's Hospital
Apatinib Plus IE Chemotherapy (Ifosfamide and Etoposide) for Relapsed or Refractory Osteosarcoma	NCT04824352	Effect of Drug Toxicity, Drug	apatinib	12 Years - 70 Years	Peking University People's Hospital
Apatinib for Inoperable Advanced Chondrosarcoma	NCT04260113	Efficacy Toxicity, Drug	Apatinib Mesyla...	-	Peking University People's Hospital
Neoadjuvant Chemoradiotherapy Combined With Camrelizumab and Nimotuzumab for Esophageal Squamous Cell Carcinoma	NCT05355168	Toxicity, Drug	neoadjuvant che...	18 Years - 75 Years	Anhui Provincial Hospital
Apatinib + Ifosfamide and Etoposide for Relapsed or Refractory Osteosarcoma	NCT04690231	Effect of Drug Toxicity, Drug Secondary Resis...	Apatinib Mesyla... ifosfamide and ...	3 Years -	Peking University People's Hospital
Comparison of MAPI+Camrelizumab Versus API+Apatinib Versus MAPI in Patients With a Poor Response to Preoperative Chemotherapy for Newly Diagnosed High-grade Osteosarcoma	NCT04351308	Osteosarcoma Survival Chemotherapy Ef... Toxicity, Drug	MAPI chemothera... Apatinib Mesyla... Camrelizumab	12 Years -	Peking University People's Hospital

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