Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Pembrolizumab

Albumin-Bound Paclitaxel

Olaparib

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

1. Neoadjuvant phase; Treatment 1: Pembrolizumab+ Paclitaxel + Carboplatin (Cycles 1-4) Treatment 2: Pembrolizumab + Olaparib (Cycles 1-4)
2. Definitive Surgery
3. Adjuvant phase; Pembrolizumab + Olaparib (1-9 cycles)

Note: each cycle = 3 weeks (Neoadjuvant Treatment 1 and 2, and Adjuvant Treatment)

200 mg fixed dose, IV, every 3 weeks (Q3W), on Days 1 of Cycles 1-4

80 mg/m2, IV, weekly, on Days 1, 8, 15 of Cycles 1-4

Area under the curve (AUC 1.5), intravenously (IV), weekly, on Days 1, 8, 15 of Cycles 1-4

Each subject will undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant treatment.

Definitive Surgery

Yuko Takahashi, MD., PhD.

Hironobu TAN, PhD.

Masaya Hattori, MD., PhD.

Kumiko Kida, MD., PhD.

This is a Phase II, single-arm, open label study to evaluate Olaparib plus Pembrolizumab following platinum-based chemotherapy plus Pembrolizumab as neoadjuvant therapy for germline BRCA (gBRCA) 1/2 mutated triple negative breast cancer (TNBC).

Pembrolizumab in combination with weekly paclitaxel and carboplatin (treatment 1) is followed by Pembrolizumab in combination with Olaparib (treatment 2) in neoadjuvant setting and Pembrolizumab in combination with Olaparib in adjuvant setting will be studied

Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1/2 Mutated Triple Negative Breast Cancer

Neoadjuvant and Adjuvant Olaparib Plus Pembrolizumab Following Platinum Based Chemotherapy Plus Pembrolizumab for Germline BRCA Mutated Triple Negative Breast Cancer (WJOG14020B/OPERETTA)

Pathological complete response rate (ypT0/TisypN0) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery.

Residual Cancer Burden (RCB) 0/1 rate is defined as the proportion of subjects on evaluation from routine pathologic sections of the primary breast tumor and the regional lymph nodes after the completion of neoadjuvant therapy assessed by the local pathologist at the time of definitive surgery. Six variables are included in a calculation formula. The calculated RCB index value can also be categorized as one of four RCB classes (0 - 3). The calculation formula and detailed description can be found at a dedicated Web site: http://www.mdanderson.org/breastcancer_RCB.

Pathological complete response rate (ypT0/is) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen regardless of regional lymph nodes status following completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery.

The Proportion of Three Year-Overall Survival (3y-OS) is defined as the proportion of survival subjects without death due to any cause at 3 years from registration. Subjects without documented death at the time of the analysis will be censored at the date of the last follow-up.

The Proportion of Three-Year Distant Metastatic Free Survival (3y-DMFS) is defined as the proportion of survival subjects without distant metastatic disease at 3 years from registration. Subjects without documented distant metastatic disease at the time of the analysis will be censored at the date of the last follow-up.

The Proportion of Three-Year Disease Free Survival (3y-DFS) is defined as the proportion of survival subjects without metastatic disease and secondary malignancy at 3 years from registration. Subjects without documented metastatic disease and secondary malignancy at the time of the analysis will be censored at the date of the last follow-up.

Safety measurements are the incidence of, causality of, and outcome of AEs/SAEs; and changes in vital sign measurements and laboratory values.

Merck Sharp & Dohme LLC

Okayama University

Assistant professor, Endocrinological Center

Rare Diseases

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Infective Agents

Micronutrients

Hematinics

Vitamins

Doxorubicin

Liposomal doxorubicin

Methotrexate

Cisplatin

Ifosfamide

Isophosphamide mustard

Mechlorethamine

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Folinic Acid

Folate

Vitamin B9

Immediate pre surgical chemotherapy treated with four drugs including doxorubicin, cisplatin, high-dose methotrexate (MTX) and ifosfamide in eleven weeks, and then definitive surgery followed by adjuvant chemotherapy according to chemotherapy regimen in Peking University People's Hospital(PKUPH).

Immediate definitive surgery, and then post operative chemotherapy based on doxorubicin, cisplatin, high-dose MTX and ifosfamide according to chemotherapy regimen in PKUPH.

60mg/m\^2, in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH

100mg/m\^2, in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH

High dose of methotrexate (8-12g/m\^2), in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH

12g/m\^2, in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH

Including limb-sparing procedure and amputation

definitive surgery

chemotherapy that given before definitive surgery

pre surgical chemotherapy

Jie Xu, M.D.

Xie Lu, M.D.

Wei Guo

To study the effect of the timing of surgery on outcome of patients with nonmetastatic osteosarcoma of pelvis and sacrum.

Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma of pelvis and sacrum have included surgery with adjuvant chemotherapy. Pre-surgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of pre-surgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy, especially in the axial region. The contribution of chemotherapy and surgery timing has not been tested rigorously. To study the effect of the timing of surgery on outcome of patients with nonmetastatic osteosarcoma of pelvis and sacrum, we conducted multicenter randomized trial to determine whether chemotherapy administered before definitive resection of primary tumors improved EFS and overall survival compared with traditional resection of the primary tumor followed by adjuvant chemotherapy.

Timing of Surgery in Nonmetastatic Osteosarcoma of the Pelvis and Sacrum

Presurgical Chemotherapy Compared With Immediate Surgery and Adjuvant Chemotherapy for Nonmetastatic Osteosarcoma of the Pelvis and Sacrum

Calculated from the date of treatment start until death, whichever comes first.

Calculated from the date of treatment start until the time of disease progression or death, whichever comes first.

The percentage of tumor necrosis calculated in the resected specimen in Arm 2.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1/2 Mutated Triple Negative Breast Cancer	NCT05485766	Triple Negative... Triple Negative... Breast Neoplasm... Breast Cancer BRCA1 Mutation BRCA2 Mutation BRCA Mutation BRCA-Associated...	Pembrolizumab Paclitaxel Carboplatin Olaparib Definitive Surg...	18 Years -	Okayama University
Timing of Surgery in Nonmetastatic Osteosarcoma of the Pelvis and Sacrum	NCT03360760	Osteosarcoma of...	Doxorubicin Cisplatin Methotrexate Ifosfamide definitive surg... pre surgical ch...	10 Years - 40 Years	Peking University People's Hospital

Spots Global Cancer Trial Database for definitive surgery