Precision Oncology in Advanced Pancreatic Cancer
This clinical trial determines the feasibility of providing and implementing personalized therapy options using the OncoTreat platform in patients with pancreatic cancer that cannot be removed by surgery (unresectable) and have not yet received treatment. The OncoTreat software is designed to use a patient’s tumor tissue sample to potentially provide a list of treatment options that would be most effective for that patient. This approach may work better than the usual approach to determine effective treatment options for patients with pancreatic cancer.
Inclusion Criteria
- PART 1: Be willing and able to provide written informed consent for the trial
- PART 1: Have histologically or cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma or be willing to undergo a biopsy with confirmed pathology prior to starting therapy
- PART 1: Have untreated disease that is unresectable due to being metastatic or locally advanced without potential of surgery as assessed by the treating physician
- PART 1: Subjects who have documented disease recurrence greater than 6 months after completing neoadjuvant or adjuvant chemotherapy for limited disease will be eligible for the study
- PART 1: Have a predicted life expectancy of greater than 6 months
- PART 1: Subjects must have a plan to obtain a new core biopsy of a primary and/or metastatic lesion planned as part of routine care for which consent is obtained separately or (b) consent to be biopsied to satisfy the tissue requirements of this protocol
- PART 2 INCLUSION CRITERIA
- Be willing and able to provide written informed consent for the trial
- Age >= 18 years of age on day of signing informed consent
- Have histologically or cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma
- Have a predicted life expectancy of greater than 3 months
- Have measurable disease based on RECIST v1.1
- Have a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) performance scale within 3 days of first dose of study drug
- Have documented radiographic progression to or documented intolerance of first- or second-line systemic treatment for locally advanced, unresectable or metastatic disease
- Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication (female subjects of childbearing potential). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication (male and female subjects of childbearing potential)
- Leukocytes >= 2,000 /mcL
- Absolute neutrophil count (ANC) >= 1,500 /mcL
- Platelets >= 100,000 /mcL
- Hemoglobin >= 9 g/dL without transfusion or erythropoietin (EPO) dependency within 7 days
- Creatinine =< 1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN * Glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)
- Total bilirubin =< 2 mg/dL or direct bilirubin =< ULN for those with total bilirubin > 2 X ULN. Subjects with Gilbert Syndrome will be eligible if total bilirubin is < 3.0 mg/dL
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
- Albumin > 3.0 mg/dL
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants
- aPTT =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
Exclusion Criteria
- PART 1: Has previously received neoadjuvant or adjuvant chemotherapy for pancreatic cancer unless greater than 6 months has passed since completion of adjuvant or neoadjuvant chemotherapy and initiation of therapy for recurrent or metastatic disease
- Part 2 EXCLUSION CRITERIA
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy, or herbal/complementary oral or intravenous (IV) medicine, within 2 weeks of the first dose of treatment
- All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0 or baseline prior to administration of first dose of study drug. Subjects with toxicities attributed to prior anti-cancer therapy that are not expected to resolve and result in long-lasting sequalae, such as chronic neuropathy after platinum-based therapy, are permitted to enroll
- Has received chemotherapy or radiotherapy within 14 days of first dose of study medication
- Has a solid organ or hematologic transplant
- Has experienced weight loss > 10% over 2 months prior to first dose of study therapy
- Has a diagnosed additional malignancy within 2 years prior to first dose of trial treatment with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin or curatively resected in situ breast cancers. Subjects with another malignancy diagnosed > 2 years prior to the first dose of trial medication who were treated with curative intent and are not undergoing active therapy will be eligible
- Has an active infection requiring systemic therapy
- Has clinically relevant ascites (defined as requiring paracentesis within 21 days of first dose of study drug) or with moderate radiographic ascites. A minimal amount of radiographic ascites is allowed
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the investigator, including dialysis
- Has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
- EXCLUSION CRITERIA SPECIFIC TO CAPECITABINE: Requires concomitant use of phenytoin and/or warfarin due to reported increases in serum phenytoin levels and the international normalized ratio (INR) in patients receiving concomitant phenytoin and warfarin, respectively
- EXCLUSION CRITERIA SPECIFIC TO CAPECITABINE: Has a known hypersensitivity to capecitabine or to any of its components
- EXCLUSION CRITERIA SPECIFIC TO CAPECITABINE: Has a known hypersensitivity to 5-fluorouracil
- EXCLUSION CRITERIA SPECIFIC TO IMATINIB: Requires concomitant use of anticoagulation with warfarin. Patients who require anticoagulation should receive low molecular weight heparin
- EXCLUSION CRITERIA SPECIFIC TO IMATINIB: Has a left ventricular ejection fraction (LVEF) of < 45%
- EXCLUSION CRITERIA SPECIFIC TO IMATINIB: Has New York Heart Association (NYHA) class III or IV symptoms
- EXCLUSION CRITERIA SPECIFIC TO IMATINIB: Has a history of ventricular tachycardia, ventricular fibrillation, ventricular flutter, Torsades de Pointes, or long QT syndrome
- EXCLUSION CRITERIA SPECIFIC TO RUXOLITINIB: Has a history of hypersensitivity to ruxolitinib or to any medicine with similar chemical compounds
- EXCLUSION CRITERIA SPECIFIC TO RUXOLITINIB: Has a baseline corrected QT interval (QTc) > 470 ms
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04476537.
PRIMARY OBJECTIVES:
I. To determine the feasibility of administering personalized therapy to subjects with advanced pancreatic cancer utilizing the novel OncoTreat platform. (Part 1)
II. To assess the feasibility of implementing the OncoTreat framework in patients with newly diagnosed, untreated locally advanced, unresectable or metastatic pancreatic adenocarcinoma. (Part 1)
III. To evaluate the overall feasibility of using the OncoTreat technology to inform rational selection of off-label Food and Drug Administration (FDA)-approved or investigational drugs in subjects with advanced pancreatic cancer (pancreatic ductal adenocarcinoma [PDA]) who have progressed on one or two prior lines of systemic therapy. (Co-primary Objective, Part 2)
IV. To evaluate the clinical efficacy of OncoTreat by assessing the objective response rate (ORR) for subjects with advanced PDA treated with OncoTreat-prioritized drugs after disease progression on one or two prior lines of systemic therapy according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. (Co-primary Objective, Part 2)
SECONDARY OBJECTIVES:
I. To describe the OncoTreat profiling of a pre-treatment biopsy in pancreatic cancer. (Part 1)
II. To evaluate preclinical efficacy for candidate treatments using patient-derived models. (Part 1)
III. To identify a suitable drug for use in a subsequent phase I clinical trial (separate protocol). (Part I)
IV. To describe the safety and tolerability of using OncoTreat to inform rational treatment decision in subjects with advanced PDA who have progressed on one or two prior lines of therapy. (Part 2)
V. To assess the efficacy of OncoTreat by estimating the disease control rate (DCR) at 16 and 24 weeks, the median progression-free survival (PFS), the overall survival (OS), and the cancer antigen (CA) 19-9 tumor marker response. (Part 2)
VI. To assess the pharmacokinetics of each OncoTreat-prioritized agent in subjects with advanced PDA. (Part 2)
EXPLORATORY OBJECTIVE:
I. Evaluate patient level data including tumor and patient information that may predict for rapid tumor growth or prolonged response to first line treatment in metastatic pancreatic cancer. (Part 1)
II. To explore the relationship between drug exposure, pharmacodynamics, efficacy, and safety of each OncoTreat-prioritized agent. (Part 2)
III. To assess whether the master regulator signature, using Visualization Pipeline for ribonucleic acid sequencing (RNA-seq) analysis (VIPER) analysis, in a given subject’s tumor changes in response to standard-of-care treatment by comparing initial and secondary biopsies collected for each subject before and after one or two lines of systemic therapy (chemotherapy or clinical trial). (Part 2)
IV. Using the same data as in the bullet point above, assess the frequency with which chemotherapy treatments alter the predicted sensitivity of tumors to other OncoTreat-prioritized agents (p-value < 1 x 10^-5). (Part 2)
V. To compare the standard-of-care clinical deoxyribonucleic acid (DNA) mutation analysis results with matched master regulator activity profiles to correlate any clinically actionable genomic information with the top OncoTreat-prioritized drugs. (Part 2)
VI. To evaluate the feasibility of using the OncoTreat technology on peripheral blood circulating tumor cells (CTCs) by comparing master regulators generated from CTCs to those obtained from tumor tissue in matched pre- and on-treatment samples with an OncoTreat-informed agent. (Part 2)
VII. To identify associations between master regulator profiles and additional clinical, epidemiological, physiological, imaging, or molecular features of the subject or subject’s tumor. (Part 2)
VIII. To identify potential biomarkers, beyond the master regulator signature, using additional genomic, RNA, protein, and imaging platforms that are predictive or prognostic of response to each OncoTreat-prioritized agent (p-value < 1 x 10^-5). (Part 2)
OUTLINE:
Patient’s tumor tissue is tested and evaluated via OncoTreat platform to identify medications for clinical use that may help treat their cancer. Results are reviewed by experts on a Precision Medicine Tumor Board (PMTB) for recommendation of specific treatments.
Trial PhaseNo phase specified
Trial Typetreatment
Lead OrganizationNYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
Principal InvestigatorGulam Abbas Manji
- Primary IDAAAR6703
- Secondary IDsNCI-2020-06834
- ClinicalTrials.gov IDNCT04476537