Genetic Analysis of Blood and Tissue Samples From Patients With Advanced Cancer, Moonshot Study

PRIMARY OBJECTIVES:

I. To procure paired newly acquired tumor tissues and blood at baseline and upon progression in patients treated for advanced cancer with molecularly targeted therapies at National Cancer Institute Community Oncology Research Program (NCORP) sites.

II. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free deoxyribonucleic acid \[DNA\] analysis), and nucleic acids from patients in the Biorepository, which is the Biopathology Center (BPC) at Nationwide Children's Hospital (NCH), that may be used to study mechanisms of sensitivity and resistance to cancer therapies.

III. To bank, when available, optional snap-frozen tissue (for future to be determined analysis) from patients in the Biorepository, which is the Biopathology Center (BPC) at Nationwide Children's Hospital (NCH), that may be used to study mechanisms of sensitivity and resistance to cancer therapies.

IV. To assess the feasibility of obtaining paired high-quality newly acquired tumor tissues and blood from patients being treated for advanced cancer in community-based healthcare settings (NCORP sites).

SECONDARY OBJECTIVES:

I. To perform molecular profiling assays on matched malignant tumor and blood (including but not limited to whole exome and messenger ribonucleic acid \[RNA\] sequencing) in order to provide physicians and patients with a clinical report from a Clinical Laboratory Improvement Act (CLIA)-certified laboratory from tumor obtained at baseline and upon progression that may be used to guide further treatment planning.

II. To make available biospecimens for studies to define potential resistance biomarkers using genomic and proteomic-based assessment platforms.

III. To contribute genetic analysis data from coded specimens to Genomic Data Commons, a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data including presentation, diagnosis, staging, summary treatment, and outcome, if possible.

IV. To identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned.

V. To identify resistance mechanisms using genomic DNA- and RNA-based assessment platforms.

OUTLINE:

Patients undergo collection of blood and tumor prior to starting treatment and upon disease progression (second collection of blood and tumor only for patients who do not continue to progress and achieve either an objective response \[OR\] or stable disease \[SD\] after 6 months of treatment). Samples are banked and analyzed via next generation sequencing.

• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Specimen Collection: Undergo collection of blood and tissue

Primary outcomes

• Obtaining tumor tissue and blood specimens [Up to 2 years]: Will obtain tumor tissue and blood specimens for biobanking and to store tissues, blood, and nucleic acids for future research, including the study of matched pre and post-treatment tumor biopsies to elucidate mechanisms of resistance. Cases will be grouped according to histology and/or treatment.

Secondary outcomes

• Tumor tissues storage in the Biopathology Center (BPC) at Nationwide Children's Hospital (NCH) (Biorepository) [Up to 2 years]
• Genomic analysis [Up to 2 years]: Will perform genomic studies, including a pan-cancer gene panel, and contribute molecular data to the genomic data commons.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patient meets all eligibility criteria for treatment of the tumors with the agents listed and has agreed to provide tissue and blood samples for this study

  * Targeted therapy maybe as a singular/monotherapy or in combination with any Food and Drug Administration (FDA)-approved chemotherapies
  * Patient's primary or recurrent disease is targeted-treatment naive or will be treated with a targeted therapy listed different from any previously-received targeted therapy or combination therapy as standard of care
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Patients with a PS of 2 may be enrolled only at the discretion of the treating physician and radiologist
* Have an advanced malignancy being treated with one of the agents listed. Advanced cancer is cancer that is unlikely to be cured or controlled with treatment. The cancer may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body. Treatment may be given to help shrink the tumor, slow the growth of cancer cells, or relieve symptoms. Patients may be undergoing first or subsequent lines of therapy. In the case where an agent not listed is newly approved for one of the listed tumors, patients undergoing therapy with it will be able to enroll at discretion of the principal investigator (PI). This is to avoid any lag between FDA approval of a previously investigational agent and protocol modifications/updates
* Have an advanced malignancy that meets one of the following criteria:

  * Patients must have tumor amenable to image guided or direct vision biopsy and be willing and able to undergo a tumor biopsy for molecular profiling. The biopsy must not be associated with a significant risk of severe or major complications or death. In particular, endoscopic, open or laparoscopic surgical procedures are not to be performed to provide research specimens. However, research specimens may be provided if the patient needs to undergo such procedures for clinical reasons
  * Severe or major complications are considered to be those

    * Requiring therapy, minor hospitalization (more than overnight but < 48 hours \[h\])
    * Requiring major therapy; unplanned increase in level of care, prolonged hospitalization > 48 h
    * Resulting in permanent adverse sequelae
    * Resulting in death
  * Patient will be undergoing a procedure due to medical necessity during which the tissue may be collected. The following tumors may be collected only under the conditions specified and not for the sole purpose of the clinical trial:

    * Brain biopsies: ONLY if the patient has medical necessity for craniotomy for clinical care
    * Mediastinal, laparoscopic, gastrointestinal, or bronchial endoscopic biopsies: ONLY to be obtained incidentally to a clinically necessary procedure

Exclusion Criteria:

* Uncontrolled intercurrent illness that in the physician's assessment would pose undue risk for biopsy
* Patients currently enrolled or planning to be co-enrolled (while participating on the 10231 study) on a therapeutically interventional clinical trial aimed to treat the current malignancy
* If the patient is on chronic anticoagulation treatment, they must be able and willing to have this treatment discontinued for the biopsy. Discontinuation procedures will be those of the treating site

44 more sites not listed.

• S. P Ivy, Principal investigator, National Cancer Institute (NCI)