To evaluate the efficacy of XL184 in subjects with one of the following advanced solid tumors: a. Breast Cancer b. Gastric and Gastroesophageal Junction Cancer c. Hepatocellular Carcinoma (HCC) d. Melanoma e. Non-small Cell Lung Cancer f. Ovarian, primary peritoneal or fallopian tube Carcinoma g. Pancreatic Cancer h. Castration-Resistanct Prostate Cancer (CRPC)
Conditions
Interventions
Product Name: XL184
Product Code: XL184
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Cabozantinib
CAS Number: 1140909-48-3
Sponsors
Exelixis Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject has a cytologically or histologically and radiologically confirmed, advanced, recurrent, or metastatic solid tumor of the nine types listed below The following limitations on prior systemic anticancer treatments apply: • The maximum number of prior systemic treatment regimens apply to the advanced, recurrent, or metastatic disease state. • Unless otherwise specified in a i, determination of the number of prior treatments will be based on the following: • Prior systemic treatments include standard and investigational chemotherapy and targeted therapies (including targeted biologic therapies). • Neoadjuvant, adjuvant, hormonal, or locally administered therapy (including embolization, ablation), radiotherapy, and immunotherapy do not count towards these restrictions. • Retreatment with the same systemic regimen is counted as one regimen. Specific restrictions to tumor histology and prior systemic anticancer treatment are as follows: --NOTE: specific conditions apply to all following subsections a to i, please check Protocol- not displayed here due to space restriction- a. Breast Cancer b. Gastric and Gastroesophageal Junction Cancer c. Hepatocellular carcinoma (HCC) d. Melanoma e. Non-small cell lung cancer f. Ovarian, primary peritoneal or fallopian tube carcinoma g. Pancreatic cancer h. Castration-Resistant Prostate Cancer (CRPC) i. Small Cell Lung Cancer 2. The subjects must have evidence of progressive disease (PD) by investigator assessment on CT, MRI, or bone scan: a. For RDT cohorts: per mRECIST 1.0. b. For NRE cohorts: per mRECIST 1.1; or criteria specified in inclusion criteria #1(v) for CRPC. c. Newly diagnosed subjects without prior treatment, if allowed per tumor-specific inclusion criterion 1, are exempt from these criteria. 3. Subjects having any tumor type other than CRPC must have at least one lesion that is not within a previously irradiated field and is measurable on CT or MRI scan: a. For RDT cohorts: per mRECIST 1.0. b. For NRE cohorts: per mRECIST 1.1. 4. The subject has recovered to baseline or CTCAE = Grade 1 from toxicities related to prior treatment, except alopecia, lymphopenia, other non-clinically significant AEs, including AEs attributed to androgen deprivation therapy for CRPC subjects. 5. The subject is = 18 years old on the day of consent. 6. Archival tumor tissue, (unstained sections, paraffin block, or frozen tumor tissue) has been requisitioned for shipment to the central laboratory, unless prohibited by local regulatory bodies including Institutional Review Boards (IRBs). Alternatively, a new tumor sample may be obtained. SCLC subjects, clinically diagnosed HCC subjects, and any subjects diagnosed = 7 years prior to the date of screening with no additional tumor tissue collected in the last 7 years are excluded from this requirement. 7. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. The subject has organ and marrow function as follows: --NOTE: specific c
Exclusion criteria
Exclusion criteria: 1. The subject has experienced clinically-significant hematemesis or hemoptysis of > 0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment. 2. The subject has cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel. 3. The subject has received: a. Any systemic chemotherapy (including investigational agents) within 4 weeks (with the exception of nitrosoureas/ mitomycin C within 6 weeks), of the first dose of study treatment , OR b. Biological agents (antibodies, immune modulators, cytokines, or vaccines) within 6 weeks of the first dose of study treatment, OR c. Hormonal anticancer therapy (not including LHRH agonists or antagonists) within 2 weeks before the first dose of study treatment. For CRPC subjects, specific restrictions on prior hormonal and other anticancer treatments are detailed in inclusion criterion 1h (vi), OR d. Small-molecular kinase inhibitors or any other type of investigational agent within 4 weeks before the first dose of study treatment or 5 half-lives of the compound or active metabolite, whichever is shorter. 4. The subject has received radiation therapy within 2 weeks of the first dose of study treatment except as follows: a. Radiation therapy to the thoracic cavity (unless radiation targets bone metastases ), within 3 months. b. Prior radionuclide treatment within the last 6 months. 5. The subject has initiated treatment with or changed drugs used to control loss of bone mass (eg, bisphosphonates) within 4 weeks prior to the first dose of study treatment. 6. The subject has symptomatic or uncontrolled brain metastasis or epidural disease requiring current treatment including steroids and anti-convulsants. Neurosurgical resection of brain metastasis or brain biopsy is permitted if completed at least 3 months before the first dose of study treatment. 7. The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results that are above (or 1.3 x) the laboratory upper limit of normal. 8. The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) >500 ms at screening. 9. The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents (eg, clopidogrel). Low dose aspirin (= 81 mg/day), low-dose warfarin (=1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted. 10. The subject has uncontrolled or significant intercurrent illness including, but not limited to, the following conditions: • Cardiovascular disorders such as symptomatic congestive heart failure (CHF), uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment (blood pressure [BP] must be controlled at screening), unstable angina pectoris, clinically-significant cardiac arrhythmias, history of stroke (including transient ischemic attack [TIA] or other ischemic event) within 6 months of study treatment, myocardial infarction within 6 months of study treatment, history o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is: - To evaluate the efficacy of XL184 in subjects with advanced solid tumors ; Timepoint(s) of evaluation of this end point: MRI, CT, and/or bone scans will be performed at baseline and every 6 weeks ; Secondary Objective: The secondary objectives of this study are: - To evaluate the safety and tolerability of XL184 in subjects with advanced solid tumors - To correlate the pathway dysfunction of desease-related genes or proteins such as MET and downstream signaling molecules with clinical outcome - To further characterize the pharmacokinetic (PK) and pharmacodynamic parameters of XL184 -To evaluate the safety and efficacy ofcabozantinib at two starting dose levels (100 mg and 39.4 mg once daily [qd]) The exploratory objective of this study is: - To identify surrogate biomarkers associated with clinical activity ; Primary end point(s): Primary Endpoints: Randomized Discontinuation Trial (RDT) Cohorts: Lead-in Stage: • Objective Response Rate (ORR) per Modified Response Evaluation Criteria in Solid Tumors mRECIST(version 1.0), per investigator Randomized Stage: • Progression-free survival (PFS), per investigator Non-Randomized Expansion (NRE) Cohorts: • Castration-resistant Prostate Cancer (CRPC) subjects: Bone scan response per IRF (primary analysis; Section 5.5.11.4) and investigator • Non-CRPC subjects: ORR per mRECIST (version 1.1) per Independent Radiology Facility (IRF) (primary analysis) and investigator (supportive analysis) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Every 12 weeks; Secondary end point(s): All tumor type cohorts unless otherwise specified: • Bone scan response in RDT cohorts, per IRF • ORR (per mRECIST 1.0) in the Randomized Stage, per investigator • Duration of response, per investigator (all cohorts) and IRF (NRE cohorts) • PFS (NRE cohorts), per investigator and IRF • Overall survival • Changes in tumor markers CRPC NRE cohorts: • ORR (per mRECIST 1.1), per IRF and investigator, among subjects with baseline measurable disease • Changes in pain and in analgesic medication • Skeletal-related events (SREs) • Biomarker and laboratory assessments, including circulating tumor cells (CTCs), hemoglobin and hematocrit measurements, and markers of bone metabolism including serum bone-specific alkaline phosphatase (ALP), CTx (carboxy-terminal collagen crosslinks), and NTx (N-telopeptide crosslinks) Safety endpoints include adverse events (AEs) and clinical laboratory parameters. | — |
Countries
Belgium, Israel, Taiwan, United Kingdom, United States
Outcome results
None listed