Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Small Cell Lung Carcinoma

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Durvalumab

Tremelimumab

Antineoplastic Agents, Immunological

Durvalumab monotherapy: Durvalumab (1500 mg intravenous \[IV\]) q4w in combination with placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with placebo saline solution.

Durvalumab in combination with tremelimumab: Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with tremelimumab.

Placebo: Placebo saline solution (IV) q4w in combination with a second placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by a single placebo saline solution q4w. The first placebo saline solution monotherapy dose q4w will be 4 weeks after the final dose of the 2 placebo saline solutions in combination.

Placebo

Haiyi Jiang, M.D.

This is a Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients with LS-SCLC Who Have Not Progressed Following Concurrent Chemoradiation Therapy

Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy

A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients With Limited Stage Small Cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of PFS

To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of OS

To assess the efficacy of Durvalumab \& Tremelimumab combination therapy vs Placebo in terms of OS

To assess the efficacy of durvalumab and tremelimumab combination therapy compared to placebo in terms of PFS

To investigate the relationship between PDL1 expression \& spatial distribution with Durva (mono) therapy \& Durva+Treme (combination) therapy

AstraZeneca

Etoposide

Etoposide phosphate

Enzyme Inhibitors

In this arm, 30 patients with limited-stage small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with etoposide and platinum chemotherapy. And those resectable after neoadjuvant therapy will be treated with surgery. Postoperative patients receive two cycles of toripalimab and JS004 combined with etoposide and platinum chemotherapy. then patients received maintenance treatment with toripalimab and JS004 until the disease progressed.

JS004

Toripalimab

Patients with resectable tumors after neoadjuvant therapy will be treated with surgery.

surgery

Platinum

Peng Zhang, PhD

Tao Ge, PhD

For limited-stage small cell lung cancer (SCLC), neoadjuvant chemotherapy plus PD-1 antibody is recommended. However, most patients cannot achieve a complete pathological response (CPR). A new immunotherapeutic strategy is needed to achieve a higher CPR rate. JS004 is a new antibody targeting B and T lymphocyte attenuator (BTLA), which restrains immune cells\&#39; function and leads to immune escape of tumor cells. The combination of PD-1 and BTLA antibodies has shown a good therapeutic effect in solid tumors. This trial aims to investigate the efficacy and safety of the therapeutic regimen of toripalimab and JS004 plus etoposide and platinum Chemotherapy in limited-stage SCLC.

All enrolled patients received toripalimab and JS004 Combined With etoposide and platinum Chemotherapy.

Neoadjuvant Therapy With Toripalimab and JS004 Combined With Etoposide and Platinum Chemotherapy for Limited-stage Small Cell Lung Cancer : A Phase 2 Trial

Neoadjuvant Therapy With Toripalimab and JS004 Combined With Etoposide and Platinum Chemotherapy for Limited-stage Small Cell Lung Cancer : A Single-arm, Phase 2 Trial

The researchers will consider whether IPD is available to other researchers only after the paper is published.

PCR rate is defined as the proportion of participants who have achieved pathologic complete response (on routine hematoxylin and eosin staining, no tumor cell can be found in tumor bed or lymph node) in all participants.

ORR is defined according to the RECIST v1.1 criteria.

MPR rate is defined as the proportion of participants who have achieved major pathologic response (on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants.

TRAE is defined and classified according to NCI-CTCAE v5.0 in all participants.

Event-free survival (EFS) is defined as the length of time (months) from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. Progression is defined 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 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

It is defined as the time (months) from enrollment to death of participant due to any cause. In the case of a patient who still survives at the time of analysis, the date of last contact will be taken as the censoring date.

The assessment is made according to the Quality of Life Scale for Lung Cancer Patients (EORTC-QLQ-C30, Version 3). EORTC's QLQ-C30 (V3.0) is a core scale for lung cancer patients, with a total of 30 items. Among them, Item 29 and 30 are divided into seven grades, which are assigned with 1 to 7 scores according to the answer options. The other items are divided into 4 grades: Not at All, A Little, Quite a Bit, and Very Much, assigned with 1 to 4 scores respectively. The higher score, the worse quality.

Shanghai Pulmonary Hospital, Shanghai, China

Director

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Brentuximab Vedotin

Vinblastine

Dacarbazine

Anti-Bacterial Agents

Antibiotics, Antitubercular

Immunotoxins

Immunoconjugates

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine

2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg

Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine

Adriamycin, vinblastine, and dacarbazine

Jeremy Abramson, M.D.

Brentuximab is an antibody-drug conjugate (ADC), which is the combination of an antibody (a protein that binds to cells) and a chemotherapy molecule. Brentuximab works by using the antibody portion to enter into the Hodgkin lymphoma cells and then releasing the chemotherapy portion, which attempts to destroy the cell.

The intravenous chemotherapy drugs Adriamycin, Vinblastine and Dacarbazine (AVD) which you will receive in this research study are approved for use in people with Hodgkin Lymphoma. A drug called bleomycin is usually included with AVD, but since it appears to be a less effective drug with significant potential risks, it is being replaced in this study with the drug brentuximab.

In this research study, the investigators are looking to see whether brentuximab in combination with AVD is effective in treating limited-stage Hodgkin Lymphoma.

Each treatment cycle is 28 days. You will receive brentuximab alone on Day 1 and 15 of the first cycle (lead-in cycle). After cycle 1, you will receive brentuximab combined with AVD on Day 1 and 15 for 4-6 cycles, depending on your response to therapy. Brentuximab and AVD will be given to you by intravenous infusion (IV).

The following test and procedures will be performed on Days 1 and 15 of each cycle:

* Review of any side effects you have experienced and all medications you are taking
* Performance Status
* Physical exam and vital signs
* Routine blood tests
* Questionnaire to evaluate symptoms of neuropathy
* Research blood sample to look at markers to see how your body is responding to study medication
* PET-CT scan prior to completing cycle 2 of combination brentuximab/AVD

After the final dose of the study drug: The following assessments will be performed within one month of your last dose of study medication:

* Review of any side effects you have experienced and all medications you are taking
* Performance Status
* Physical exam and vital signs
* Routine blood tests
* Questionnaire to evaluate symptoms of neuropathy
* Research blood sample to look at markers to see how your body is responding to study medication
* PET-CT scan Follow up will include the following
* Review of any side effects you have experienced and all medications you are taking
* Performance Status
* Review and Physical exam
* Routine blood tests
* Questionnaire to evaluate symptoms of neuropathy
* CT scans

Brentuximab Vedotin Plus AVD in Limited-stage Hodgkin Lymphoma

Brentuximab Vedotin Plus AVD in Non-bulky Limited Stage Hodgkin Lymphoma

Complete response rate at the end of therapy as measured by Positron emission tomography-computed tomography (PET/CT). Response is evaluated using Revised International Working Group Criteria. Complete response is defined as disappearance of all evidence of disease.

The number of participants achieving a Partial Response (PR) or Complete Response (CR) after one cycle of Brentuximab monotherapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria.

* CR: Disappearance of all evidence of disease
* PR: Regression of measurable disease and no new sites

The number of participants achieving a Partial Response (PR) or Complete Response (CR) at the end of therapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria.

* CR: Disappearance of all evidence of disease
* PR: Regression of measurable disease and no new sites

A summary of the grade 3 or 4 adverse events experienced by participants as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The data is shown as the number of participants that experienced at least one grade 3 or 4 adverse event for each of the specified toxicities.

Beth Israel Deaconess Medical Center

Dana-Farber Cancer Institute

H. Lee Moffitt Cancer Center and Research Institute

Seagen Inc.

Massachusetts General Hospital

Principal Investigator

Adverse events were assessed with regularly scheduled physical exams, laboratory tests, and participant self reports.

Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine

Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg

Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine

Treatment Arm

Age, Continuous

20 - 30 years

31 - 40 years

41 - 60 years

61 - 75 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

More Than One Race

Other

White

Race/Ethnicity, Customized

United States

Region of Enrollment

Lugano Classification of disease stage

* Stage I: Found in only 1 lymph node or lymphoid organ or the cancer is found in only 1 area of a single organ outside the lymph system.
* Stage II: The cancer is found in 2 or more lymph node areas on the same side of the diaphragm or the cancer extends locally from one lymph node area into a nearby organ

Can be assigned a letter A or B. B is when a patient has any of the following symptoms:

* Loss of \> than 10% of body weight over the previous 6 months without dieting
* Unexplained fever of at least 100.4°F (38°C)
* Drenching night sweats

Stage

Hypercellular

Hypocellular

Normocellular

Missing

Hypercellular indicates more cells are being produce than expected, hypocellular means that fewer than expect number of cells are being produced, normocellular means an approximately normal amount of cells are being produced

Cellularity

Classical Hodgkin Lymphoma, NOS

Lymphocytic Rich

Mixed Cellularity

Nodular Sclerosis

The histological subtypes of classic Hodgkin lymphoma:

* Classical NOS: Not Otherwise Specified (specific subtype not identified)
* Lymphocyte-Rich: Rarely found in more than a few lymph nodes and usually occurs in the upper half of the body
* Mixed Cellularity: Seen predominantly in adults, this is the second most common type. It can start in any lymph node but most often occurs in the upper half of the body.
* Nodular Sclerosis: The most common type in developed countries. This most common in teens and young adults. Tends to start in lymph nodes in the chest or neck.

Histology

Early Favorable

Early Unfavorable

Early Unfavorable: Stage I or II disease and one or more of the following risk factors:

* B Symptoms (see stage description)
* Extranodal disease
* Bulky disease (≥10 cm or \>33% of the chest diameter on chest x-ray)
* Three or more sites of nodal involvement
* Sedimentation rate of ≥50 mm/h

Early Favorable: Stage I or II disease with none of the risk factors listed above. Patients with favorable classification tend to have better outcomes.

Risk Class

Information is missing for one participant

Number of Lesions

Longest Tumor Diameter

Jeremy Abramson, MD

Two participants were not evaluated for response due to a death and a withdrawal.

Complete Response Rate

Overall Response Rate After One Cycle of Brentuximab

Complete Response

Partial Response

Overall Response Rate

Peripheral sensory neuropathy

Neutrophil count decreased

Fatigue

Nausea

Anemia

White blood cell decreased

Abdominal pain

Diarrhea

Febrile neutropenia

Vomiting

Mucositis oral

Weight loss

Dehydration

Hypertension

Infections and infestations - Other, specify

Blood and lymphatic system disorders - Other, spec

Grade III or IV Adverse Events

Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine (AVD)

Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg

Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine

Overall Study

Cisplatin

For patients who are randomized to study arm, (i.e. to irradiate the post-chemotherapy tumor extent) the clinical target volume-tumor (CTV-T) includes the post-chemotherapy gross tumor volume-tumor (GTV-T) with a margin of 0.8 cm.

Chemotherapy includes etoposide 100mg/m2 d1-d3 combine with cisplatin 80mg/m2 d1 at 21-day interval for 4 cycles.

Radiotherapy will be administered with cycle 3 chemotherapy（1.5 Gy twice daily to 45 Gy in 30 fractions over 3 weeks）

For patients who are randomized to control arm, (i.e. to irradiate the pre-chemotherapy tumor extent) the clinical target volume-tumor (CTV-T) includes the pre-chemotherapy gross tumor volume-tumor (GTV-T) with a margin of 0.8 cm.

Chemotherapy includes etoposide 100mg/m2 d1-d3 combine with cisplatin 80mg/m2 d1 at 21-day interval for 4 cycles.

Radiotherapy will be administered with cycle 3 chemotherapy (1.5 Gy twice daily to 45 Gy in 30 fractions over 3 weeks).

1.5 Gy twice daily to 45 Gy in 30 fractions over 3 weeks for both arms

hyperfractionated radiation therapy for both arms

Ming Chen, MD

Hui Liu, MD. PHD

Yong Bao, MD

We hypothesized that the local control for both arms were not statistically significant, when irradiation to the post-induction chemotherapy tumor volume is compared with irradiation to the pre-induction chemotherapy tumor volume.While elective nodal irradiation will be omitted for both arms.

A Prospective Randomized Study Comparing the Target Volume for Limited-stage Small Cell Lung Cancer

Omitting Elective Nodal Irradiation and Irradiating Post-induction Versus Pre-induction Chemotherapy Tumor Extent for Limited-stage Small Cell Lung Cancer

Sun Yat-sen University

Zhejiang Cancer Hospital

Imidazole

The following procedures will take place during study visits beginning after the screening procedures:

- Participants will receive combination therapy:

* Brentuximab Vedotin intravenously on predetermined days per cycle
* Adriamycin intravenously on predetermined days per cycle
* Dacarbazine intravenously on predetermined days per cycle

Adriamycin

Limited stage Hodgkin lymphoma is a highly curable disease, but standard treatment with ABVD chemotherapy and radiation can lead to late risks of secondary cancers, lung injury, heart injury, and others. This trial eliminates radiation therapy and reduces intensity of chemotherapy by incorporating the highly active FDA-approved targeted therapy brentuximab vedotin, an antibody-drug conjugate specifically against the lymphoma cells, combined with the standard chemotherapy drugs Adriamycin and Dacarbazine (AD).

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved brentuximab vedotin (brentuximab) as part of the initial treatment of Hodgkin lymphoma. Currently, brentuximab is FDA-approved for treatment of relapsed Hodgkin lymphoma.

* Brentuximab works by binding specifically to Hodgkin lymphoma cells, entering the cells, and then releasing the drug to destroy the cell.
* The chemotherapy drugs Adriamycin and Dacarbazine (AD) which which participants will receive in this research study are approved for use in people with Hodgkin Lymphoma.
* Patients will not receive planned radiation therapy, or the drugs bleomycin or vinblastine.

Brentuximab Vedotin Plus AD in Non-bulky Limited Stage Hodgkin Lymphoma

The number of patients that achieved a complete response (CR) to therapy as assessed by the revised International Working Group Criteria.

Complete response:

* Lymph nodes and extralymphatic sites: Score 1, 2, or 3 with or without a residual mass on 5-point (Daeuville) scale
* Bone Marrow: No evidence of FDG-avi disease
* No new lesions

Deauville Criteria for PET scan Interpretation in Lymphoma

Five-point scale:

1. No Uptake
2. Uptake ≤ mediastinum
3. Uptake \>mediastinum but ≤ liver
4. Uptake moderately increased compared to liver at any site
5. Uptake markedly increased compared to the liver at any site or/and new sites of disease

The number of patients that achieved a complete Metabolic Response (CR) or Partial Metabolic Response (PR) to therapy as assessed by the revised International Working Group Criteria.

Complete Metabolic Response:

Lymph nodes and extralymphatic sites: Score 1, 2, or 3 with or without a residual mass on 5-point (Daeuville) scale Bone Marrow: No evidence of FDG-avi disease No new lesions

Partial Metabolic Response:

\>Lymph nodes and extralymphatic sites: Score 4, 5 with reduced uptake compared with baseline and residual mass(es) of any size.

Deauville Criteria for PET scan Interpretation in Lymphoma

Five-point scale:

1. No Uptake
2. Uptake ≤ mediastinum
3. Uptake \>mediastinum but ≤ liver
4. Uptake moderately increased compared to liver at any site
5. Uptake markedly increased compared to the liver at any site or/and new sites of disease

The number of patients that experienced grade III and grade IV adverse events that were deemed to be possibly, probably, or definitely related to study treatment. Adverse events were assessed using Common Toxicology Criteria for Adverse Events (CTCAE v4.0) criteria.

The following procedures will take place during study visits beginning after the screening procedures:

- Participants will receive combination therapy:

* Brentuximab Vedotin intravenously on predetermined days per cycle
* Adriamycin intravenously on predetermined days per cycle
* Dacarbazine intravenously on predetermined days per cycle

Brentuximab Vedotin

Adriamycin

Dacarbazine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy	NCT03703297	Small Cell Lung...	Durvalumab Tremelimumab Placebo	18 Years - 130 Years	AstraZeneca
Neoadjuvant Therapy With Toripalimab and JS004 Combined With Etoposide and Platinum Chemotherapy for Limited-stage Small Cell Lung Cancer : A Phase 2 Trial	NCT06256237	Limited Stage S...	JS004 Toripalimab surgery Etoposide Platinum	18 Years -	Shanghai Pulmonary Hospital, Shanghai, China
Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy	NCT03703297	Small Cell Lung...	Durvalumab Tremelimumab Placebo	18 Years - 130 Years	AstraZeneca
Brentuximab Vedotin Plus AVD in Limited-stage Hodgkin Lymphoma	NCT01534078	Hodgkin Lymphom...	Brentuximab Ved... Adriamycin, vin...	18 Years -	Massachusetts General Hospital
A Prospective Randomized Study Comparing the Target Volume for Limited-stage Small Cell Lung Cancer	NCT01731548	Carcinoma of Lu... Small Cell Limited Stage	hyperfractionat...	18 Years - 75 Years	Zhejiang Cancer Hospital
Brentuximab Vedotin Plus AD in Non-bulky Limited Stage Hodgkin Lymphoma	NCT02505269	Hodgkin Lymphom...	Brentuximab Ved... Adriamycin Dacarbazine	18 Years -	Massachusetts General Hospital
The Study Of An Oral Drug Called A Radiation Sensitizer In Patients With Newly Diagnosed Small Cell Lung Cancer (SCLC)	NCT00043862	Lung Cancer, Sm... Small Cell Lung...	topotecan	18 Years -	GlaxoSmithKline

Spots Global Cancer Trial Database for limited stage