Personalized Cancer Therapy in Treating Participants with Metastatic or Unresectable Cancers
This pilot trial studies how well personalized cancer therapy works in treating participants with cancer that has spread to other places in the body or cannot be removed by surgery. Personalized cancer therapy is the practice of making decisions about what kind of treatment participants should receive based on the genetic makeup of the tumor. Genes in your body encode certain characteristics such as height, eye and hair color. Researchers believe that abnormal genes in tumors may affect how individuals respond to cancer treatments. Collecting information about tests and treatments received will help researchers describe if patients respond better when their physicians choose to treat them according to the genetic makeup of their tumor.
- Patients with incurable malignancies with >= 50% 2-year cancer-associated mortality (as estimated by two physician and where appropriate according to 2014 NCDB data); diseases include, but are not limited to: * Ampullary carcinoma * Appendiceal cancer * Colorectal cancer (CRC) * Extrahepatic cholangiocarcinoma (EHCC) * Esophageal adenocarcinoma * Gallbladder cancer (GBCA) * Gastric adenocarcinoma * Head and neck cancer * Hepatocellular carcinoma (HCC) * Intrahepatic cholangiocarcinoma (IHCC) * Melanoma * Non-KIT GIST (gastrointestinal stromal tumor) * Non-small cell lung cancer (NSCLC) * Ovarian cancer * Pancreatic ductal adenocarcinoma (PDAC) * Sarcoma (high-grade) * Small bowel adenocarcinoma (including duodenal) * Triple-negative breast cancer (TNBC) * Urothelial cancer ** Note: we will limit gastrointestinal malignancies to no more than 65% of the case mix
- Patients with cancer of unknown primary or a rare tumor (i.e., fewer than 15 cases per 100,000 per year) with no approved therapies; (patients in this inclusion criteria must meet all other exclusion and inclusion criteria except inclusion criteria #1)
- Patients with incurable malignancies, irrespective of 2-year mortality, who, in the opinion of the investigator have no treatment option expected to yield significant clinical benefit
- Patients must have at least one of the following for a diagnosis/disease status: * Unresectable disease * Metastatic disease * Medically unfit for surgical resection but with an expected survival of > 3 months, Eastern Cooperative Oncology Group (ECOG) < 2 and New York Heart Association (NYHA) status =< II * Disease where no conventional therapy leads to a survival benefit > 6 months in the respective cohort and line of therapy for which the patient is otherwise eligible * Actionable alterations determined by FoundationOne
- Treatment naive for his or her newly diagnosed malignancy for enrollment to groups 1 or 2
- Status post 1 or more unmatched systemic therapy regimens for enrollment to group 3
- Ability to understand and the willingness to sign a written informed consent
- Patients must have measurable disease for malignancies: defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, positron emission tomography (PET)-CT, magnetic resonance imaging (MRI), or calipers by clinical exam
- ECOG performance status 0-1
- New York Heart Association (NYHA) functional classification I-II
- Absolute neutrophil count >= 1.5 x 10^9/L
- Platelet count >= 100 x 10^9/L
- Total bilirubin =< 2.0 x institution’s upper limit of normal (ULN)
- Patients without underlying liver disease * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 X institutional upper limit of normal
- Serum creatinine =< 2.0 x institution’s ULN or 24-hour creatinine clearance >= 50 ml/min
- At the time of treatment, patients should be off other anti-tumor agents for at least 5 half-lives of the agent or 3 weeks from the last day of treatment, whichever is shorter to enroll in group 3; patients must not have been treated with anti-tumor agents to enroll in group 1 or group 2; patients must be off prior antibody therapy for at least 3 half-lives before starting treatment; patients may enroll on study even while receiving treatment
- Able to swallow and retain oral medication if needed
- Patients must have evaluable tissue/blood for testing as specified by the concurrent FoundationOne criteria; this will be obtained during the standard of care tumor diagnosis and tumor staging evaluation
- Female patients of childbearing potential must have a negative serum pregnancy test and agree to use at least one form of pregnancy prevention during the study and for at least one month after treatment discontinuation; for the purposes of this study, child- bearing potential is defined as: all female patients that were not in post-menopause for at least one year or are surgically sterile (site-specific criteria applying to Avera only)
- Male patients must use a form of barrier pregnancy prevention approved by the investigator / treating physician during the study and for at least one month after treatment discontinuation (site-specific criteria applying to Avera only)
- Two oncologists disagree on prognosis or resectability
- Severe or uncontrolled medical disorder that would, in the investigator’s opinion, confound study analyses of treatment response (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements)
- Are pregnant or breast-feeding patients or any patient with childbearing potential not using adequate pregnancy prevention (site-specific criteria applying to Avera only)
Locations & Contacts
Trial Objectives and Outline
I. To determine the feasibility of using molecular testing to determine targeted therapy for patients with newly diagnosed (groups 1 and 2) and previously treated (group 3) cancers with incurable biology (>= 50% 2-year cancer-associated mortality as estimated by two oncologists and where appropriate according to 2014 National Cancer Database [NCDB] data) after their treating physician receives recommendations based upon genomic analysis for molecular alterations.
I. Assess the ability to enroll patients in groups 1, 2 and 3.
II. Assess the turnaround time for genomic analysis.
III. Assess the ability to identify actionable genomic alterations.
IV. Assess the ability of treating physicians to wait for molecular information in order to start treatment.
V. Assess the ability to obtain insurance coverage in order for patients to receive molecularly targeted matched treatment based on genomic analysis.
I. Assess the activity of molecularly targeted matched treatment and physician’s choice of traditional systemic chemotherapy treatment.
II. Assess the incidence of grade 3-5 adverse events in molecularly targeted matched treatment and physician’s choice of traditional systemic chemotherapy treatment.
OUTLINE: Participants undergo genetic testing and are assigned to 1 of 2 arms.
ARM A (MATCHED THERAPY):
GROUPS 1 & 2: Participants who are treatment naive and have unresectable or metastatic disease receive 1 or more drugs that target molecular alterations (Investigation of molecular Profile-Related Evidence Determining Individualized Cancer Therapy [I-PREDICT] regimen) for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Participants those with complete response (CR) or partial response (PR) continue I-PREDICT regimen in the absence of a decline to stable disease (SD) or progressive disease (PD), the tumor becomes resectable, or unacceptable toxicity. Participants with PD or SD then cross-over Arm B. Participants who crossed-over to Arm B, then crossed back over to Arm A and demonstrated a 10-29% decrease in tumor size after first 8 weeks of treatment, may continue I-PREDICT regimen in the absence of a decline to SD or PD, the tumor becomes resectable, or unacceptable toxicity.
GROUP 3: Participants who have metastatic or unresectable disease and have received at least one prior therapy receive I-PREDICT regimen for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Participants with CR or PR continue I-PREDICT regimen in the absence of a decline to SD or PD, the tumor becomes resectable, or unacceptable toxicity.
ARM B (UNMATCHED THERAPY): Participants receive physician's choice of systemic chemotherapy for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Participants with PD in Arm B and SD but short of PR while receiving the I-PREDICT regimen in Groups 1 & 2, Arm A, may then cross back over to Arm A.
After completion of study treatment, participants are followed up every 3 months.
Trial Phase & Type
No phase specified
University of California San Diego
Jason K. Sicklick
Secondary IDs NCI-2018-00243
Clinicaltrials.gov ID NCT02534675