A Phase II, Randomized, Active-Controlled, Multi-Center Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Guided by Genomic Profiling Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site Who Have Received Three Cycles of Platinum Doublet Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 529
- 试验地点
- 125
- 主要终点
- Progression Free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)
研究概览
简要总结
This study will compare the efficacy and safety of molecularly-guided therapy versus standard platinum-containing chemotherapy in participants with poor-prognosis cancer of unknown primary site (CUP; non-specific subset) who have achieved disease control after 3 cycles of first-line platinum based induction chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically-confirmed unresectable cancer of unknown primary site (CUP) diagnosed according to criteria defined in the 2015 European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for CUP
- •No prior lines of systemic therapy for the treatment of CUP
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Candidate for platinum-based chemotherapy (according to the reference information for the intended chemotherapy)
- •At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
- •Formalin-Fixed Paraffin-Embedded (FFPE) tumor tissue sample </= 4 months old that is expected to be sufficient for generation of a comprehensive genomic profile at a central reference pathology laboratory
排除标准
- •Squamous cell CUP
- •Participants who can be assigned to a specific subset of CUP for which a specific treatment is recommended by the 2015 ESMO Clinical Practice Guidelines for CUP or with a clinical and IHC profile indicative of a specific primary tumor (favorable prognosis CUP subsets): Poorly differentiated carcinoma with midline distribution; women with papillary adenocarcinoma of the peritoneal cavity; women with adenocarcinoma involving only the axillary lymph nodes; squamous cell carcinoma of the cervical lymph nodes; poorly differentiated neuroendocrine tumors; men with blastic bone metastases and elevated prostate-specific antigen (PSA); participants with a single, small, potentially resectable tumor; colon cancer-type CUP, including participants with a CK7 negative, CK20 positive, CDX-2 positive immunohistochemistry profile; CK7-positive, CK20-negative and TTF-1 positive tumors in a context suggestive of lung adenocarcinoma or thyroid cancer; IHC profile definitely indicative of breast cancer OR an IHC profile indicative of breast cancer and either a history of breast cancer or lymph nodes in the drainage areas of the breast; high-grade serious carcinoma histology and elevated CA125 tumor marker and/or a mass in the gynecological tract or any tumor mass or lymph node in the abdominal cavity; IHC profile suggestive of renal cell carcinoma and renal lesions, with a Bosniak classification higher than IIF; IHC profile compatible with cholangiocarcinoma or pancreatobiliary (or upper gastrointestinal carcinoma) AND 1 or 2 liver lesions without extrahepatic disease or with only pulmonary metastases and/or lymph nodes in the drainage areas of the liver
- •Known presence of brain or spinal cord metastasis (including metastases that have been irradiated only)
- •Histology and immunohistology profiles (per 2015 ESMO guidelines) that are not adenocarcinoma or poorly differentiated carcinoma/adenocarcinoma
- •History or known presence of leptomeningeal disease
- •Known human immunodeficiency virus (HIV) infection
- •Significant cardiovascular disease
- •Prior allogeneic stem cell or solid organ transplantation
- •Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or for up to 7 months after the final dose of treatment
研究组 & 干预措施
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Alectinib (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Vismodegib (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Ipatasertib (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Olaparib (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Erlotinib (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Bevacizumab (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Vemurafenib (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Cobimetinib (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Trastuzumab Subcutaneous (SC) (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Pertuzumab (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Atezolizumab (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Paclitaxel (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Entrectinib (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Ivosidenib (Drug)
Molecularly-Guided Therapy
Participants will be assigned to molecularly-guided therapy based on genomic profile.
干预措施: Pemigatinib (Drug)
Platinum-Based Chemotherapy
Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).
干预措施: Trastuzumab Subcutaneous (SC) (Drug)
Platinum-Based Chemotherapy
Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).
干预措施: Pertuzumab (Drug)
Platinum-Based Chemotherapy
Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).
干预措施: Carboplatin (Drug)
Platinum-Based Chemotherapy
Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).
干预措施: Paclitaxel (Drug)
Platinum-Based Chemotherapy
Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).
干预措施: Cisplatin (Drug)
Platinum-Based Chemotherapy
Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Progression Free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)
时间窗: From randomization to the first occurrence of disease progression or death from any cause, until 330 PFS events were observed (approx. 4.3 years for MGT Cat 1 and 3.4 years for Chemotherapy Cat 1).
This efficacy objective was to evaluate the efficacy of MGT vs platinum chemotherapy in term of PFS in participants with CUP whose best response to 3 cycles of platinum induction chemotherapy was assessed CR, PR, or SD.
次要结局
- Overall Survival (OS)(From randomization to death from any cause (approx. 4 years))
- Objective Response Rate (ORR)(Two consecutive occurrences of complete or partial response >/=4 weeks apart (up to approximately 4 months))
- Duration of Response (DOR)(From the first documentation of a complete response (CR) or partial response (PR) to disease progression or death from any cause, whichever occurs first (up to approximately 4 years))
- Disease Control Rate (DCR)(From randomization to death from any cause, through the end of study (approximately 4 years))