NCT04811703Phase 1Recruiting
Hospices Civils de Lyon · Hôpital Claude Huriez - Chirurgie générale et digestive, Lille
Women with a history of tumor response insufficient to allow complete cytoreductive surgery after three cycles of prior neoadjuvant systemic carboplatin-paclitaxel chemotherapy will be prospectively enrolled in this phase I study. After providing written informed consent and confirmation of unresectable disease by multidisciplinary assessment, patients will undergo three cycles of combined chemotherapy consisting of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with doxorubicin and cisplatin at escalating dose levels, combined with systemic intravenous chemotherapy using carboplatin and paclitaxel at standard doses. Treatment cycles will last 28 days, with PIPAC administered on Day 1 and systemic chemotherapy on Day 8, for a maximum of three cycles in the absence of unacceptable toxicity.
Dose escalation of PIPAC chemotherapy will follow a Continual Reassessment Method (CRM) algorithm. The first patient will be treated at the lowest dose level, and subsequent patients will receive the recommended dose according to the CRM, conditional on the occurrence of dose-limiting toxicity (DLT) observed during Cycle 1. From dose level 7 onward, corresponding to cisplatin and doxorubicin doses associated with an increased risk of renal toxicity, sodium thiosulfate will be systematically administered prior to each PIPAC procedure for its nephroprotective effect, in accordance with the cisplatin dose level and current clinical practice.
The primary objective of the study is to determine the maximum tolerated dose (MTD) of doxorubicin-cisplatin administered by PIPAC and to define the recommended dose for a subsequent phase II trial. DLTs will be actively collected and reviewed as soon as they are identified during the first treatment cycle.
Secondary objectives include evaluation of pathological response, radiological tumor response, and changes in the extent of peritoneal disease following combined chemotherapy, as well as characterization of the pharmacokinetics of PIPAC-administered drugs. Additional exploratory objectives include assessment of the KELIM parameter as a predictive marker of sensitivity to combined chemotherapy and evaluation of the overall safety profile of the treatment strategy.
On Day 1 of the first treatment cycle, blood samples will be collected for pharmacokinetic analysis of doxorubicin and cisplatin. Serum CA-125 levels will be measured before each intraperitoneal or intravenous chemotherapy administration throughout the study. At the end of combined chemotherapy, radiological tumor assessment by CT scan or MRI and a final CA-125 measurement will be performed. Patients achieving complete response, partial response, or stable disease according to RECIST v1.1 criteria will undergo re-evaluation for surgical resectability. If complete cytoreductive surgery is deemed feasible, surgery will be scheduled with a post-operative follow-up visit planned one month later. Patients with progressive or persistently unresectable disease will discontinue study participation.
Eligibility: 18 Years to 75 Years · Female · * Age ≥ 18 years and ≤ 75 years;
* ECOG Performance Status 0-2;
* Histologically confirmed epithelial carcinoma of the ovary, fallopian tubes, or peritoneum, FIGO stage IIb to IVa, with a tumor response after three cycles of carboplatin-paclitaxel that does not correspond to disease progression but is insufficient to allow complete cytoreductive surgery, as assessed by the investigators after multidisciplinary tumor board discussion and validation;
* Adequate hematological function:
* Absolute neutrophil count \> 1,500/mm³ (or 1.5 × 10⁹/L);
* Hemoglobin ≥ 9.0 g/dL;
* Platelet count \> 100 × 10⁹/L;
* Adequate renal and hepatic function:
* Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or estimated glomerular filtration rate ≥ 60 mL/min/1.73 m² (CKD-EPI equation);
* Total bilirubin ≤ 1.5 × ULN;
* AST and ALT ≤ 1.5 × ULN (≤ 5 × ULN in patients with liver metastases);
* No unstable medical conditions, including myocardial infarction within 6 months prior to study entry, congestive heart failure, unstable angina, active cardiomyopathy, unstable arrhythmia, uncontrolled hypertension, uncontrolled psychiatric disorders, severe infection, peptic ulcer disease, or any condition that could be worsened by the study treatment or impair compliance, as judged by the investigator;
* Written informed consent obtained prior to any study-specific procedures;
* Patient affiliated with a national health insurance system.
NCT05255471Phase 3Recruiting
National Cancer Institute, Naples · IRCCS Istituto Nazionale Tumori di Napoli, Naples
MITO 35b is designed as randomized, open label, phase III trial that aims to assess the efficacy of olaparib maintenance beyond progression compered to standard platinum-based chemotherapy after secondary cytoreductive surgery.
The target population of this study are ovarian cancer patients who experience a disease recurrence or progression to a first line maintenance therapy with PARPi; at progression patients must have received a secondary cytoreduction according to clinical practice.
Eligibility: 18 Years to · Female · * Signed informed consent prior to any study specific procedures;
* Female, age ≥ 18 years at time of signing informed consent
* Patients with high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer recurrent or progressive after first line PARPi maintenance are allowed;
* Patients must have received only one previous line of a platinum containing regimen not containing bevacizumab;
* Patient must have received a first-line maintenance therapy with a PARPi for at least 6 months, if the prior PARPi used was olaparib then patients must have received treatment without significant toxicity or the need for a permanent dose reduction.Patients who experience disease relapse after the end of the 24 months maintenance therapy are eligible;
* Patients must have undergone secondary cytoreductive surgery. The cytoreduction must result in complete resection (absence of macroscopic residual tumor) or at least resection of the progressive lesion(s) occurring during maintenance;
* Documented BRCA1/2 status. Both mutated and wild type patients are eligible. Patient with unknown status of BRCA genes agrees to undergo analysis of their germline and somatic BRCA status (testing must be completed prior to enrolment in the study);
* Patients must have a life expectancy ≥ 16 weeks;
* Patients must start the experimental treatments in the current study within 3 to 8 weeks from second surgery;
* ECOG performance status 0 to 1;
* Patient must provide archival tumor samples formalin fixed, paraffin embedded (FFPE) from both the primary and secondary surgeries for paired analysis. A quality control analysis of samples will be performed before patient's randomization;
* Patient must be able to take oral medications;
* Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
* Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
* Platelet count ≥ 100 x 109/L
* Total serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) and Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x ULN for the institution (or ≤ 5x ULN if liver metastases are present)
* Patients must have creatinine clearance estimated of ≥51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test: Estimated creatinine clearance = (140-age \[years\]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72 (a where F=0.85 for females.
* Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on Day 1 Cycle 1. Postmenopausal is defined as:
* Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50;
* radiation-induced oophorectomy with last menses \>1 year ago;
* chemotherapy-induced menopause with \>1-year interval since last menses;
* surgical sterilisation (bilateral oophorectomy or hysterectomy).
* Women of childbearing potential and their partners, who are sexually active, must agree to the use of one highly effective forms of contraception and their partners must use a male condom, during the treatment and for at least 1 months after last dose of olaparib.For chemotherapy drugs, please refer to fertility section of corresponding Summary of Product Characteristics (SCP);
* Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures;
NCT06050109Phase IIRecruiting
Hongmei Zheng, PhD · Wu Xinhong, Wuhan, Hubei
To observe and evaluate the clinical efficacy and safety of continuous use of OFS for premenopausal patients with early breast cancer after 5 years use of OFS.
This study is a multicenter, prospective, observational, non randomized controlled, open-label real world study based on hospital medical record system data, aimed at evaluating the benefits of continuing to use OFS after 5 years of use. The retrospective analysis plan includes patient data from September 1, 2023 to September 1, 2026. Join two cohorts: the continued use group and the discontinued use group after 5 years of OFS, respectively.
Eligibility: 18 Years to 60 Years · Female · * Diagnosed with early primary breast cancer
* Female aged 18-60 years (including 18 year and 60 year)
* Hormone receptor (HR) positive HER2 negative
* Receive 5 years of OFS treatment
* ECOG score 0-1
* Voluntarily join this study and sign the informed consent form;
* The researcher believes that it can benefit.
NCT06939023NARecruiting
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Amsterdam UMC, Amsterdam
The DIPLOMA-3 trial is an international, multicenter, patient-blinded randomized controlled trial comparing laparoscopic and robot-assisted left-sided pancreatectomy. Patients with an indication for elective left-sided pancreatecomy for benign or premalignant lesions in the body or tail of the pancreas and considered eligible will be randomized between laparoscopic and robot-assisted resection.
Eligibility: 18 Years to · All · * Age at least 18 years;
* Indication for elective left-sided pancreatectomy, either spleen-preserving or non-preserving (because of proven or suspected left-sided benign or premalignant disease);
* Both robot-assisted and laparoscopic left-sided pancreatectomy are technically feasible for resection, according to the local treatment team;
* Fit to undergo left-sided pancreatectomy according to the surgeon and anaesthesiologist;
* Written informed consent
NCT07262957Phase 4Recruiting
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Amsterdam UMC, Amsterdam
The PANENCA trial aims to reduce postoperative complications in patients undergoing pancreatoduodenectomy (also known as a Whipple procedure), a complex surgical operation performed to remove tumors located in or near the head of the pancreas. One of the most frequent and serious complications after this surgery is postoperative pancreatic fistula (POPF), a leakage of pancreatic fluid from the surgical connection. POPF can lead to intra-abdominal infection, bleeding, and inflammation, often resulting in delayed recovery and postponement of subsequent oncological treatment. In severe cases, these complications may be life-threatening.
Patients with a small main pancreatic duct (3 millimeters or less) are known to have a substantially higher risk of developing POPF. Previous studies have shown that several existing interventions may reduce the risk or severity of these complications. These include hydrocortisone, a medication that suppresses postoperative inflammation; octreotide, a medication that reduces the production of pancreatic secretions; and a surgical technique known as the ligamentum teres hepatis patch, which uses the patient's own tissue to protect nearby blood vessels in the event of a pancreatic leak.
Because the development of pancreatic fistulas is multifactorial, the investigators hypothesize that a combined approach targeting different underlying mechanisms may provide a complementary and more effective protective effect than any single intervention alone. The PANENCA trial therefore evaluates whether the combined use of hydrocortisone, octreotide, and the ligamentum teres patch can reduce the rate of major postoperative complications after pancreatoduodenectomy.
Patients participating in the study are randomly assigned to receive either the combination treatment in addition to standard perioperative care or standard perioperative care alone. The study medications are administered only during the first postoperative days, and the surgical patch is applied during the operation itself. No additional tests, monitoring procedures, or hospital visits are required beyond routine clinical care.
This international, multicenter randomized trial includes patients at high risk for POPF who are undergoing pancreatoduodenectomy. The primary objective is to determine whether the combination treatment reduces the incidence of major postoperative complications. If proven effective, this bundle approach may be implemented more consistently across participating countries and incorporated into international clinical guidelines for pancreatic surgery.
Eligibility: 18 Years to · All · * Elective pancreatoduodenectomy for any indication (both minimally invasive and open)
* Pancreatic duct diameter ≤ 3mm on preoperative CT or MRI\*
* 18 years of age or older
* Signature of informed consent
* In the opinion of the investigator, the patient is eligible for the administration of hydrocortisone and octreotide, based on contraindications, warnings, and precautions as listed in the respective SmPCs
NCT07117045Phase IIRecruiting
Changhai Hospital · Meinian Onehealth Healthcare Holdings Co., Ltd, Shanghai, Shanghai Municipality
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with early diagnosis crucial for improving survival. Due to the absence of effective screening methods, most patients are diagnosed at advanced stages. The population undergoing low-dose computed tomography (LDCT) screening significantly overlaps with those at high risk for PDAC; however, traditional imaging methods have limited sensitivity for detecting pancreatic lesions. This study utilizes the Pancreatic Cancer Detection with Artificial Intelligence (PANDA) system to enhance LDCT for pancreatic cancer screening in a prospective, multicenter, observational cohort. PANDA will analyze LDCT images, followed by a multidisciplinary team (MDT) reassessment of abnormal interpretations. Based on MDT evaluation, individuals will be recalled for further examination, placed under a personalized follow-up plan, or monitored for at least one year. The primary outcomes include pancreatic cancer detection rate, positive predictive value, consensus rate, and recall rate, while secondary outcomes focus on early-stage cancers, resectable tumors, and safety indicators such as false positive rates and unnecessary procedures. This study aims to assess the effectiveness and safety of AI-assisted LDCT for PDAC detection, providing a practical solution for improving public health and enhancing early diagnostic capabilities.
Eligibility: 50 Years to · All · 1. Age 50 years and above.
2. Voluntary signing of informed consent.
3. Completion of LDCT examination.
NCT03556228Phase 1, Phase 2Recruiting
VM Oncology, LLC · Providence Medical Foundation (site 209), Santa Rosa, California
This is a multicenter, open-label, Phase 1/2 study of orally administered VMD-928 monotherapy and in combination with pembrolizumab in adult subjects with advanced solid tumors or lymphoma that have progressed or are non responsive to available therapies and for which no standard or available curative therapy exists
Eligibility: 18 Years to 80 Years · All · Key
#. Histologically or cytologically confirmed diagnosis of any type of solid tumor malignancy or lymphoma:
Phase 1 Dose Escalation only: Subjects with
(A) any advanced solid tumors of
1. Head and Neck Cancers ("HNC") (of any types),
2. Esophageal cancer,
3. Lung cancers (of any types),
4. Mesothelioma,
5. Pancreatic cancers,
Or,
(B) any NTRK1 gene fusion positive ("NTRK1+") solid tumors or lymphomas, that is relapsed, refractory or intolerant (R/R/I) to standard of care (SOC) and for which there is no approved or curative therapy. Additionally, patients must not be candidates for or have exhausted regimens known to provide clinical benefit, including hematopoietic stem cell transplantation in lymphoma patients if they are deemed transplant eligible.
Phase 2 Monotherapy and Combination with Pembrolizumab only:
Subjects must have
1. TrkA-driven HNC, Esophageal, Lung, Mesothelioma, Pancreatic cancers; or,
2. any NTRK1+ solid tumors or lymphoma\*, that is R/R/I to SOC.
Key Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 or 1.
* Able to swallow and retain oral medication.
* Subjects must either have available archival tumor tissue samples, or consent to tumor tissue sampling prior to the first dose.
* Adequate organ system function as defined as follows:
1. Absolute neutrophil count ≥1.5x10\^9/L
2. Hemoglobin ≥9g/dL
3. Platelets ≥100x10\^9/L
4. PT/INR, PTT ≤1.5xULN
5. Total bilirubin ≤1.5x ULN
6. AST, ALT ≤2.5xULN
7. Creatinine ≤1.2xULN for age, weight
8. Calculated creatinine clearance or 24h urine creatinine clearance ≥60mL/min
Key
NCT06368063Phase 4Recruiting
Xi'an Jiaotong University · Zheng Wang, Xi'an, Shannxi
The study is a multicenter, prospective clinical study aimed at evaluating the efficacy and safety of Huaier Granule in postoperative adjuvant treatment of resectable pancreatic cancer
Eligibility: 18 Years to 80 Years · All · * Age range from 18 to 80 years old, regardless of gender;
* Pancreatic cancer was diagnosed by histopathology after radical surgery within 12 weeks before enrollment;
* Did not receive neoadjuvant therapy before surgery and did not receive any adjuvant therapy after surgery;
* ECOG score 0-3 points;
* Those who choose to use standard chemotherapy independently based on their own situation, or choose Huaier granules for subsequent treatment, voluntarily participate in and cooperate with various research work, including but not limited to cooperating with treatment and follow-up, cooperating with researchers for data collection, and not actively taking other treatments.
* The subjects voluntarily signed a written informed consent form before participating in this study.
NCT03218345NARecruiting
Chinese University of Hong Kong · Department of Surgery, Prince of Wales Hospital, Hong Kong
Radiofrequency ablation has been used for treatment of solid neoplasms of the liver, lung, kidney and adrenal. Recently, EUS-guided RFA has become available and the device allows EUS-guided treatment of pancreatic neoplasms. The procedure has been shown to be feasible in the porcine pancreas and was used to treat small groups of patients that are not suitable for surgery suffering from pancreatic neoplasms.
The aim of the current study is to perform a multi-center prospective study on EUS-guided radiofrequency ablation (RFA) of solid pancreatic neoplasms. The hypothesis is that EUS-guided RFA is safe, feasible and effective for treating solid pancreatic neoplasms.
Eligibility: 18 Years to · All · * Age 18 years-old or above
* Suffering from pancreatic neuroendocrine tumor or pancreatic ductal carcinoma (\<5cm in largest diameter) that was confirmed by fine needle aspiration cytology
* Unsuitable for surgery, due to one (or more) of the following items:
* ASA score \> II\*
* An alternative advanced malignancy
* Unsuitable for surgery upon expert's opinion for any other reason
* Healthy individuals who are not keen for surgical resection
* Eligible for endoscopic intervention
* Written informed consent
NCT07284277Phase 1, Phase 2Recruiting
Clinica Universidad de Navarra, Universidad de Navarra · Clínica Universidad de Navarra, Pamplona, Navarre
The purpose of this clinical trial is to assess the safety and tolerability of TTFields in combination with chemotherapy in adults with metastatic pancreatic adenocarcinoma based on treatment-emergent adverse events of chemotherapy (modFOLFIRINOX) or device (TTFields).
The main questions it aims to answer are:
* Is TTFields treatment safe for the patients in combination with modFOLFIRINOX?
* Are participants compliant with the treatment?
* Is Is TTFields treatment effective in combination with modFOLFIRINOX against metastatic pancreatic adenocarcinoma?
Eligibility: 18 Years to · All · All the patients should comply with the following criteria for inclusion:
1. Histological/cytological diagnosis of pancreatic adenocarcinoma.
2. The patient should be 18 years of age and older.
3. The patient has given consent to participate in the study.
4. The patient should be able to comply with all the requirements of the clinical trial.
5. Life expectancy of at least 3 months.
6. Metastatic disease with, at least, one hepatic lesion that must be accessible for biopsy.
7. Measurable disease as defined by Response Evaluation Criteria in Solid Tumor v1.1 (RECIST 1.1) apart from the liver lesion to be biopsied.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
9. Amenable and assigned by the investigator to receive therapy with modFOLFIRINOX.
10. Prior chemotherapy or radiotherapy on the neoadjuvant or adjuvant setting is allowed as long as at least six months have elapsed since last chemotherapy treatment.
11. Able to operate the Novo TTF-200T System independently or with the help of a caregiver.
12. Adequate hematologic and organ function, defined by the following laboratory test results, obtained during the screening period and before C1D1.
1. WBC higher than or equal to 2.5 x 10\^9/L.
2. ANC higher than or equal to 1.5 x 10\^9/L without granulocyte colony-stimulating factor support.
3. Platelet count higher than or equal to 100 x 10\^9/L without transfusion.
4. Hemoglobin higher than or equal to 9 g/dL. Patients may be transfused to meet this criterion.
5. Albumin higher than or equal to 2.5 g/dL.
6. Serum bilirubin lower than or equal to 1.5 times the upper limit of normal (ULN); patients with known Gilbert´s disease may have a bilirubin value lower than or equal to 3 x ULN.
7. INR and aPTT lower than or equal to 1.5 x ULN.
8. AST, ALT, lower than or equal to 5 x ULN.
9. Serum creatinine lower than or equal to 1.5 x ULN or Creatinine Clearance higher than or equal to 30ml/min (calculated using Cockcroft-Gault formula).
13. For women of childbearing potential: Negative serum pregnancy test within 14 days prior to C1D1. Agreement to remain abstinent (refrain from heterosexual intercourse) or use of contraceptive methods that result in a failure rate of lower than or equal to 1 percentage per year during the treatment period (combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal o transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable o implantable); intrauterine device (IUD) or intrauterine hormone-releasing system (IUS); bilateral tubal occlusion or vasectomized partner) and for at least 180 days after the last study treatment. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (higher than or equal to 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
NCT07305337NARecruiting
Zhongnan Hospital · Zhongnan Hospital of Wuhan University, Wuhan, Hubei
With the rapid advancement of biopharmaceutical technology, clinical trials have become the crucial bridge connecting new drugs from the laboratory to clinical application. Despite the increasing number of clinical trial projects being conducted, nearly all such projects face the common challenge of recruitment difficulties. Subject recruitment constitutes a pivotal stage in clinical trials; the ability to recruit a sufficient number of subjects meeting the trial requirements significantly impacts trial quality and also serves as a key factor influencing trial progress. Hematologic cancers constitute a highly heterogeneous group of malignant diseases originating in the haematopoietic organs and primarily affecting the haematopoietic system. They encompass acute and chronic leukaemias, malignant lymphomas, multiple myeloma, myelodysplastic syndromes, and related disorders. For patients facing treatment decisions, clinical trials represent not only a vital avenue for accessing cutting-edge therapies but also impose heightened demands on their capacity for informed decision-making. Conversational artificial intelligence (AI) based on large language models is rapidly advancing in health education and public health communication. Medical chatbots offer scalable and personalised advantages in delivering health information, promoting behavioural change, and enhancing patient engagement, providing a viable pathway for improving trial literacy and decision support. Accordingly, this study proposes to conduct a clinical trial literacy intervention using AI-powered chatbots among haematological malignancy patients. Through a randomised controlled trial (RCT), it aims to evaluate the impact of AI-assisted health education on patients' understanding of clinical trials and intention to participate. This research seeks to validate the application value of AI technology in health education and explore scalable AI-assisted health education intervention models.
Eligibility: 18 Years to 90 Years · All · Inclusion Criteria (1) Aged ≥18 years with clear consciousness; (2) Diagnosed with haematological malignancy meeting clinical treatment criteria (WHO criteria); (3) Capable of understanding health education content and possessing basic communication skills; (4) Willing to participate in this study and sign an informed consent form.
Exclusion Criteria
(1) Patients with concomitant cognitive impairment, psychiatric disorders, or other conditions severely affecting comprehension; (2) Anticipated hospital stay of less than 3 days, rendering completion of the intervention unfeasible; (3) End-of-life palliative care; (4) Previous participation in other clinical trial education programmes.
NCT03556228Phase 1, Phase 2Recruiting
VM Oncology, LLC · Providence Medical Foundation (site 209), Santa Rosa, California
This is a multicenter, open-label, Phase 1/2 study of orally administered VMD-928 monotherapy and in combination with pembrolizumab in adult subjects with advanced solid tumors or lymphoma that have progressed or are non responsive to available therapies and for which no standard or available curative therapy exists
Eligibility: 18 Years to 80 Years · All · Key
#. Histologically or cytologically confirmed diagnosis of any type of solid tumor malignancy or lymphoma:
Phase 1 Dose Escalation only: Subjects with
(A) any advanced solid tumors of
1. Head and Neck Cancers ("HNC") (of any types),
2. Esophageal cancer,
3. Lung cancers (of any types),
4. Mesothelioma,
5. Pancreatic cancers,
Or,
(B) any NTRK1 gene fusion positive ("NTRK1+") solid tumors or lymphomas, that is relapsed, refractory or intolerant (R/R/I) to standard of care (SOC) and for which there is no approved or curative therapy. Additionally, patients must not be candidates for or have exhausted regimens known to provide clinical benefit, including hematopoietic stem cell transplantation in lymphoma patients if they are deemed transplant eligible.
Phase 2 Monotherapy and Combination with Pembrolizumab only:
Subjects must have
1. TrkA-driven HNC, Esophageal, Lung, Mesothelioma, Pancreatic cancers; or,
2. any NTRK1+ solid tumors or lymphoma\*, that is R/R/I to SOC.
Key Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 or 1.
* Able to swallow and retain oral medication.
* Subjects must either have available archival tumor tissue samples, or consent to tumor tissue sampling prior to the first dose.
* Adequate organ system function as defined as follows:
1. Absolute neutrophil count ≥1.5x10\^9/L
2. Hemoglobin ≥9g/dL
3. Platelets ≥100x10\^9/L
4. PT/INR, PTT ≤1.5xULN
5. Total bilirubin ≤1.5x ULN
6. AST, ALT ≤2.5xULN
7. Creatinine ≤1.2xULN for age, weight
8. Calculated creatinine clearance or 24h urine creatinine clearance ≥60mL/min
Key
