Cabozantinib Plus Docetaxel and Prednisone for Advanced Prostate Cancer
Study Details
Study Description
Brief Summary
Background:
- Cabozantinib is a drug that slows the growth of blood vessels that feed tumors. It is approved for medullary thyroid cancer. However, studies have shown that prostate tumors respond to it. Docetaxel and prednisone are standard treatments for advanced prostate cancer. Researchers want to see if adding cabozantinib to these two drugs can be a safe and effective treatment for this type of cancer.
Objectives:
- To test the safety and effectiveness of cabozantinib with standard treatments for advanced prostate cancer.
Eligibility:
- Individuals at least 18 years of age who have advanced prostate cancer that has not responded to standard treatments.
Design:
-
Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will also be performed.
-
Participants will receive the cancer drugs over 21-day cycles of treatment. They will take docetaxel and cabozantinib on day 1 of each cycle. Each docetaxel infusion will take about 1 hour. They will also take prednisone by mouth twice each day.
-
Treatment will be monitored with frequent blood tests and imaging studies.
-
Participants will continue to take the study drugs for as long as their cancer does not worsen and side effects are not too severe.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
Background:
-
Docetaxel is established as first-line chemotherapy in patients with metastatic castrate resistant prostate cancer (CRPC). However; it is increasingly recognized that combining docetaxel with other agents of clinical activities without overlapping toxicities could simultaneously target different cellular signaling pathways vital for tumor survival, producing either additive or synergistic activities.
-
Inhibition of angiogenesis, either as a stand-alone approach or in combination with chemotherapy, has demonstrable antitumor efficacy against CRPC and there are several antiangiogenic agents that are now in clinical trials in this population of patients.
-
Cabozantinib (XL184) was developed as an inhibitor of both angiogenesis and of its resistance mechanism. It is an inhibitor of multiple receptor tyrosine kinases including tyrosine-protein kinase Met (c-Met), vascular endothelial growth factor receptor 2 (VEGFR2) and rearranged during transfection (RET).
-
In single agent clinical studies, cabozantinib demonstrated, broad anti-tumor activities across many solid tumor types.
Objectives:
-
To determine the safety profile of cabozantinib in combination with docetaxel and prednisone, and to determine the maximal tolerated dose (MTD) as recommended phase II dose in combination with docetaxel
-
To determine the relative efficacy (in terms of progression free survival (PFS)) of docetaxel and cabozantinib compared to docetaxel alone
Eligibility:
-
Patients must have progressive metastatic CRPC. There must be radiographic evidence of disease after primary treatment with surgery or radiotherapy. If patients had been on flutamide, they must have disease progression at least 4 weeks after withdrawal. Patients on bicalutamide or nilutamide must have progression at least 6 weeks after withdrawal. Withdrawal criteria apply only to patients on the above anti-androgens for at least the prior 6 months.
-
Patients must be at least 18 years of age and able to give informed consent.
-
Patients in the Phase II portion of the study must have progressed on abiraterone or enzalutamide
Design:
-
The initial phase I portion of this study will test fixed dose docetaxel and prednisone in combination with cabozantinib at three escalating doses. Using a standard 3 + 3 design, three patients will initially be treated at each dose level until MTD has been defined.
-
An expansion cohort will then be enrolled at the MTD to further characterize safety, toxicity and pharmacokinetic data and to obtain preliminary information on the efficacy of the combination treatment.
-
In Phase II, patients will be enrolled to a randomized two-arm cohort comparing docetaxel in combination with cabozantinib to docetaxel alone with a primary endpoint of PFS.
-
The accrual ceiling for the study, including the Phase I dose escalation and the expansion phases as well as the Phase II randomized phase, is set at 81.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: combination of cabozantinib, docetaxel and prednisone combination of cabozantinib, docetaxel and prednisone |
Drug: Cabozantinib
Assigned dose given daily during each 21 day cycle. Treatment may continue until disease progression or intolerable toxicity.
Other Names:
Drug: Docetaxel
75mg/m^2 intravenous (IV) over approximately 60 minutes on cycle 1 day 1 and repeated every 21 days until disease progression or intolerable toxicity.
Other Names:
Drug: Prednisone
5 mg by mouth (PO) twice a day during each 21 day cycle until disease progression or intolerable toxicity.
Other Names:
|
| Active Comparator: PII/ Arm 1-docetaxel + prednisone only docetaxel + prednisone only |
Drug: Docetaxel
75mg/m^2 intravenous (IV) over approximately 60 minutes on cycle 1 day 1 and repeated every 21 days until disease progression or intolerable toxicity.
Other Names:
Drug: Prednisone
5 mg by mouth (PO) twice a day during each 21 day cycle until disease progression or intolerable toxicity.
Other Names:
|
| Active Comparator: PII/Arm 2 -docetaxel+ prednisone + cabozantinib docetaxel+ prednisone + cabozantinib |
Drug: Cabozantinib
Assigned dose given daily during each 21 day cycle. Treatment may continue until disease progression or intolerable toxicity.
Other Names:
Drug: Docetaxel
75mg/m^2 intravenous (IV) over approximately 60 minutes on cycle 1 day 1 and repeated every 21 days until disease progression or intolerable toxicity.
Other Names:
Drug: Prednisone
5 mg by mouth (PO) twice a day during each 21 day cycle until disease progression or intolerable toxicity.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) of Cabozantinib + Docetaxel + Prednisone Compared to Docetaxel + Prednisone Alone [From start date of treatment until the date of first documented progression, date of death from any cause and up to 40 months, whichever occurred first.]
PFS is the time interval from start of treatment to documented evidence of disease progression or death. Disease progression was assessed by the Response Criteria in Solid Tumors (RECIST) and is defined as at least a 20% increase in the sum of the diameters of target lesions as referenced by the smallest sum on study. Appearance of one or more new lesions on bone scan and/or two consecutive rising prostatic-specific antigen values above the baseline at a minimum of one week intervals. A normal PSA value is 4.0 ng/ml and lower.
- Maximum Tolerated Dose (MTD) [First two cycles of treatment (each cycle is 21 days), approximately 42 days.]
MTD is defined as the dose level at which no more than 1 of 6 patients experiences a dose limiting toxicity (DLT) at the level below that which had two instances of DLT. A DLT are defined as adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) occurring during the first two cycles of therapy and related to the study medications (attributions: possible, probable, and definite) while fulfilling one of the following criteria: Any Grade 3 or greater non-hematologic toxicity except asymptomatic grade 3 hypertension, hypomagnesemia, hyponatremia, hypophosphatemia, hypocalcemia, and asymptomatic grade 4 uric acid. A treatment delay of > 2 weeks due to an adverse event (delays due to dental procedures are not included). Grade 4 neutropenia (absolute neutrophil count <500/µL lasting > 5 days. Febrile neutropenia. Grade 3 thrombocytopenia lasting for 7 days or more or thrombocytopenia < 50K/µL requiring platelet transfusion for bleeding.
Secondary Outcome Measures
- Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) [Adverse events were assessed from the date treatment consent signed to date off study, approximately 45 months and 14 days for Arm A; 43 months and 14 days for Arm B; 9 months and 11 days for DL1; 27 months and 1 day for DL2; & 11 months & 25 days for DL3]
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Other Outcome Measures
- Number of Participants With a Dose Limiting Toxicities (DLTs) [First two cycles of treatment (each cycle is 21 days), approximately 42 days.]
A DLT are defined as adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) occurring during the first two cycles of therapy and related to the study medications (attributions: possible, probable, and definite) while fulfilling one of the following criteria: Any Grade 3 or greater non-hematologic toxicity except asymptomatic grade 3 hypertension, hypomagnesemia, hyponatremia, hypophosphatemia, hypocalcemia, and asymptomatic grade 4 uric acid. A treatment delay of > 2 weeks due to an adverse event (delays due to dental procedures are not included). Grade 4 neutropenia (absolute neutrophil count <500/µL lasting > 5 days. Febrile neutropenia. Grade 3 thrombocytopenia lasting for 7 days or more or thrombocytopenia < 50K/µL requiring platelet transfusion for bleeding.
- Number of Participants Achieving Prostatic-Specific Antigen (PSA) Decline of 30% or 50% From Baseline [up to 38 months]
PSA normal range is 4 ng/ml or lower. Participants with PSA decline of 30% or 50% is the measures for prostate cancer based on conventional reporting metrics.
Eligibility Criteria
Criteria
-
INCLUSION CRITERIA:
-
Must have metastatic, progressive, castrate resistant prostate cancer (CRPC). There must be radiographic evidence of disease after primary treatment with surgery or radiotherapy that has continued to progress radiographically or biochemically (rising PSA levels on successive measurements) despite adequate androgen-deprivation therapy, which is defined as having undergone bilateral surgical castration or continued treatment on GnRH agonists or antagonists.
Progression must be evidenced and documented by any of the following parameters:
-
Two consecutively rising PSA values, above the baseline, at a minimum of 1- week intervals
-
Appearance of one or more new lesions on bone scan
-
Progressive measurable disease by RECIST 1.1
The use of androgen receptor inhibitors is not required prior to study entry. For those patients receiving an anti-androgen agent (flutamide, bicalutamide, or nilutamide), for at least 6 consecutive months immediately prior to study entry, and are entering the trial due to a rise in PSA, they must demonstrate a continued rise in PSA within 4 weeks after stopping flutamide and within 6 weeks after stopping bicalutamide or nilutamide. Flutamide, nilutamide and bicalutamide disease progression requirements only apply to patients who have been on these drugs for at least the prior 6 months.
-
Histopathological confirmation of prostate cancer by the Laboratory of Pathology of the National Cancer Institute (NCI) Pathology Department of the Walter Reed National Military Medical Center or YALE is required prior to entering this study. Patients whose pathology specimens are no longer available may be enrolled if the patient has a clinical course that is consistent with prostate cancer and available documentation from an outside pathology laboratory of the diagnosis. All efforts should be made to have the material forwarded to the research team for use in correlative studies in cases where original tissue blocks or archival biopsy material is available.
-
Patients must have metastatic disease, defined as at least one lesion on bone scan or 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 greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam.
-
Patients must have a performance status of 0 to 2 according to the ECOG criteria.
-
Patients must have adequate bone marrow, hepatic, and renal function with:
-
Hemoglobin greater than or equal to 9 grams per deciliter
-
Leukocytes greater than or equal to 3000 per microliters
-
ANC greater than or equal to 1500 per microliters, without CSF support
-
Platelets greater than or equal to 100,000 per microliters
-
AST (SGOT) less than or equal to 2.5 times upper limit of normal (ULN)
-
ALT (SGPT) less than or equal to 2.5 times upper limit of normal (ULN)
-
Total serum bilirubin less than or equal to the upper limit of normal (ULN)
-
Serum albumin greater than or equal to 2.8 grams per deciliters
-
Serum phosphorus, calcium, magnesium, and potassium greater than or equal to LLN
-
Lipase less than 2.0 times the upper limit of normal and no radiologic or clinical evidence of pancreatitis
-
Creatinine less than or equal to 1.5 times institutional upper limits of normal
OR
-
creatinine clearance of greater than or equal to 50 ml/min/1.73 m^2 for patients with creatinine levels above institutional normal by 24 hour urine.
-
urine protein/urine creatinine ratio (UPCR) less than or equal to 1
-
Patients must be at least 18 years of age. Because no dosing or adverse event data are currently available on the use of cabozantinib in combination with docetaxel and prednisone in patients less than 18 years of age, children are excluded from this study, but may be eligible for future pediatric trials
-
Patient must be capable of understanding and complying with protocol requirements and is willing to give informed consent
-
Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of XL184 administration. Sexually active subjects and their female partners must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must also agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s). Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
-
Patients enrolled on the randomized portion of the study must have had disease progression on arbiraterone or enzalutamide.
EXCLUSION CRITERIA:
-
The subject has had evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment
-
The subject is unable to swallow tablets
-
The subject has tumor invading (or there is concern for invasion of) major blood vessel
-
The subject has active brain metastases or epidural disease Subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain scans are not required to confirm eligibility.
-
The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). Low dose aspirin (less than or equal to 81 milligrams per day), low-dose warfarin (less than or equal to1 milligrams per day), and prophylactic low molecular weight heparin (LMWH) are permitted.
-
The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) greater than 500 milliseconds within 28 days before initiation of protocol therapy. Note: if initial QTcF is found to be greater than 500 milliseconds, two additional EKGs separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is less than or equal to 500 milliseconds, the subject meets eligibility in this regard.
-
Patients with contraindication to steroid use
-
Prior treatment with cabozantinib
-
The patient has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or nitrosoureas or mitomycin within 6 weeks before the first dose of study treatment.
-
The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment with the exception of patients receiving prior abiraterone or ketoconazole. For patients receiving prior abiraterone or ketoconazole, they must discontinue the medication within 5 half lives of the compound before the first dose of study treatment in order to participate in this study. Note: Subjects with prostate cancer currently receiving LHRH or GnRH agonists must be maintained on these agents.
-
The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
-
The subject has received radiation therapy:
-
to the thoracic cavity or gastrointestinal tract within 3 months before the first dose of study treatment
-
to bone or brain metastasis within 14 days before the first dose of study treatment
-
to any other site(s) within 28 days before the first dose of study treatment
-
The subject has received radionuclide treatment within 6 weeks prior to the first dose of the study treatment
-
The subject has not recovered to baseline or CTCAE less than or equal to Grade 1 from toxicity due to all prior therapies, including surgery, except alopecia and other non-clinically significant AEs.
-
The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test results at screening greater than or equal 1.3 times the laboratory ULN within 7 days before the first dose of study treatment
-
The subject has experienced any of the following:
-
clinically-significant hematemesis or gastrointestinal bleeding within 6 months before the first dose of study treatment
-
hemoptysis of greater than or equal to 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment
-
any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
-
The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
-
The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
-
Cardiovascular disorders including
-
Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening
-
Concurrent uncontrolled hypertension defined as sustained BP greater than 140 millimeters of mercury systolic, or greater than 90 millimeters of mercury diastolic despite optimal antihypertensive treatment (BP must be controlled at screening)
-
Any history of congenital long QT syndrome
-
Any of the following within 6 months before the first dose of study treatment:
-
unstable angina pectoris
-
clinically-significant cardiac arrhythmias
-
stroke (including TIA, or other ischemic event)
-
myocardial infarction
-
thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study)
-
Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
-
Any of the following within 28 days before the first dose of study treatment
-
intra-abdominal tumor/metastases invading GI mucosa
-
active peptic ulcer disease
-
inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
-
malabsorption syndrome
-
Any of the following within 6 months before the first dose of study treatment:
-
history of abdominal fistula
-
gastrointestinal perforation
-
bowel obstruction or gastric outlet obstruction
-
intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 6 months ago.
-
Other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea and esophagus.
-
Other clinically significant disorders such as:
-
active infection requiring intravenous treatment within 10 days of starting protocol
-
serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
-
history of organ transplant
-
concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
-
history of major surgery as follows:
-
Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wound complications
-
Minor surgery within 1 months of the first dose of cabozantinib if therewere no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications.
In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery
-
HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the study agents. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
-
Patients who require taking drugs that are strong inhibitors/inducers of CYP3A4 and cannot be switched to an alternative medication.
Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-thecounter medicine or herbal product.
-
Patients with greater than or equal to grade 2 peripheral neuropathy at baseline.
-
The subject has had treatment with docetaxel for the treatment of metastatic castratesensitive prostate cancer within 6 months before the first dose of study treatment.
-
The subject has had progression of prostate cancer during 6 cycles of prior docetaxel treatment for castrate sensitive disease.
-
The subject has received chemotherapy for castration-resistant prostate cancer.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | United States | 20892 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: William L Dahut, M.D., National Cancer Institute (NCI)
Study Documents (Full-Text)
More Information
Additional Information:
Publications
- Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300. doi: 10.3322/caac.20073. Epub 2010 Jul 7. Erratum in: CA Cancer J Clin. 2011 Mar-Apr;61(2):133-4.
- Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1513-20.
- Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M; Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008 Mar 1;26(7):1148-59. doi: 10.1200/JCO.2007.12.4487.
- 120204
- 12-C-0204
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 49 participants were enrolled on this study. 4 participants were screen failures and were not assigned to any treatment groups. Data is shown for 45/49 participants. 13 participants were assigned to Ph II Arm A Docetaxel & Prednisone but only 12 started treatment; one participant declined to start treatment. Data is shown for 45/49 participants. |
| Arm/Group Title | Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | Ph II Arm A: Docetaxel + Prednisone | Ph II Arm B: Cabozantinib + Docetaxel + Prednisone |
|---|---|---|---|---|---|
| Arm/Group Description | Cycle=21 days; Cabozantinib: 20 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 40 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 60 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg by mouth (PO) twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID); Cabozantinib: 40 mg by mouth (PO) everyday (QD) |
| Period Title: Overall Study | |||||
| STARTED | 4 | 8 | 7 | 13 | 13 |
| # of Patients Who Received Treatment | 4 | 8 | 7 | 12 | 13 |
| COMPLETED | 3 | 8 | 7 | 10 | 12 |
| NOT COMPLETED | 1 | 0 | 0 | 3 | 1 |
Baseline Characteristics
| Arm/Group Title | Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | Ph II Arm A: Docetaxel + Prednisone | Ph II Arm B: Cabozantinib + Docetaxel + Prednisone | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Cycle=21 days; Cabozantinib: 20 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 40 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 60 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg by mouth (PO) twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID); Cabozantinib: 40 mg by mouth (PO) everyday (QD) | Total of all reporting groups |
| Overall Participants | 4 | 8 | 7 | 13 | 13 | 45 |
| Age (Count of Participants) | ||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
50%
|
2
25%
|
1
14.3%
|
3
23.1%
|
5
38.5%
|
13
28.9%
|
| >=65 years |
2
50%
|
6
75%
|
6
85.7%
|
10
76.9%
|
8
61.5%
|
32
71.1%
|
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
59.45
(11.67)
|
66.16
(9.51)
|
70.15
(12.03)
|
67.72
(8.34)
|
68.89
(8.46)
|
67.34
(9.41)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
4
100%
|
8
100%
|
7
100%
|
13
100%
|
13
100%
|
45
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
1
7.7%
|
2
4.4%
|
| Not Hispanic or Latino |
4
100%
|
8
100%
|
6
85.7%
|
12
92.3%
|
10
76.9%
|
40
88.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
2
15.4%
|
3
6.7%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
1
2.2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
25%
|
3
37.5%
|
3
42.9%
|
5
38.5%
|
6
46.2%
|
18
40%
|
| White |
3
75%
|
5
62.5%
|
3
42.9%
|
8
61.5%
|
6
46.2%
|
25
55.6%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
1
2.2%
|
| Region of Enrollment (Count of Participants) | ||||||
| United States |
4
100%
|
8
100%
|
7
100%
|
13
100%
|
13
100%
|
45
100%
|
| Baseline Prostatic-Specific Antigen (PSA) (ng/ml) [Median (Full Range) ] | ||||||
| Median (Full Range) [ng/ml] |
182.38
|
73.71
|
166.3
|
346.9
|
65.6
|
118.4
|
| Prior Treatment with Enzalutamide or Abiraterone (Count of Participants) | ||||||
| Count of Participants [Participants] |
3
75%
|
5
62.5%
|
4
57.1%
|
8
61.5%
|
5
38.5%
|
25
55.6%
|
Outcome Measures
| Title | Progression Free Survival (PFS) of Cabozantinib + Docetaxel + Prednisone Compared to Docetaxel + Prednisone Alone |
|---|---|
| Description | PFS is the time interval from start of treatment to documented evidence of disease progression or death. Disease progression was assessed by the Response Criteria in Solid Tumors (RECIST) and is defined as at least a 20% increase in the sum of the diameters of target lesions as referenced by the smallest sum on study. Appearance of one or more new lesions on bone scan and/or two consecutive rising prostatic-specific antigen values above the baseline at a minimum of one week intervals. A normal PSA value is 4.0 ng/ml and lower. |
| Time Frame | From start date of treatment until the date of first documented progression, date of death from any cause and up to 40 months, whichever occurred first. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Four participants came off study before restaging. One participant did not start treatment. Forty participants are evaluable for PFS. No participants received carbozantinib after progression from Docetaxel and Prednisone alone. |
| Arm/Group Title | Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | Ph II Arm A: Docetaxel + Prednisone | Ph II Arm B: Cabozantinib + Docetaxel + Prednisone |
|---|---|---|---|---|---|
| Arm/Group Description | Cycle=21 days; Cabozantinib: 20 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 40 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 60 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg by mouth (PO) twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID); Cabozantinib: 40 mg by mouth (PO) everyday (QD) |
| Measure Participants | 3 | 8 | 7 | 10 | 12 |
| Median (Full Range) [months] |
8
|
13
|
6
|
10
|
6.5
|
| Title | Maximum Tolerated Dose (MTD) |
|---|---|
| Description | MTD is defined as the dose level at which no more than 1 of 6 patients experiences a dose limiting toxicity (DLT) at the level below that which had two instances of DLT. A DLT are defined as adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) occurring during the first two cycles of therapy and related to the study medications (attributions: possible, probable, and definite) while fulfilling one of the following criteria: Any Grade 3 or greater non-hematologic toxicity except asymptomatic grade 3 hypertension, hypomagnesemia, hyponatremia, hypophosphatemia, hypocalcemia, and asymptomatic grade 4 uric acid. A treatment delay of > 2 weeks due to an adverse event (delays due to dental procedures are not included). Grade 4 neutropenia (absolute neutrophil count <500/µL lasting > 5 days. Febrile neutropenia. Grade 3 thrombocytopenia lasting for 7 days or more or thrombocytopenia < 50K/µL requiring platelet transfusion for bleeding. |
| Time Frame | First two cycles of treatment (each cycle is 21 days), approximately 42 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Maximum tolerated dose was assessed only on phase 1 cohort participants. All 19 patients (e.g. 4 participants on dose level 1, 8 participants on dose level 2, and 7 participants on dose level 3) were included in the safety assessment to determine maximum tolerated dose. |
| Arm/Group Title | Ph I Cabozantinib + Docetaxel + Prednisone |
|---|---|
| Arm/Group Description | Cycle=21 days; Cabozantinib: 20 mg, 40mg, and 60 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) |
| Measure Participants | 19 |
| Number [mg] |
40
|
| Title | Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) |
|---|---|
| Description | Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
| Time Frame | Adverse events were assessed from the date treatment consent signed to date off study, approximately 45 months and 14 days for Arm A; 43 months and 14 days for Arm B; 9 months and 11 days for DL1; 27 months and 1 day for DL2; & 11 months & 25 days for DL3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in Arm A declined to participate before treatment started. |
| Arm/Group Title | Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | Ph II Arm A: Docetaxel + Prednisone | Ph II Arm B: Cabozantinib + Docetaxel + Prednisone |
|---|---|---|---|---|---|
| Arm/Group Description | Cycle=21 days; Cabozantinib: 20 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 40 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 60 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg by mouth (PO) twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID); Cabozantinib: 40 mg by mouth (PO) everyday (QD) |
| Measure Participants | 4 | 8 | 7 | 12 | 13 |
| Count of Participants [Participants] |
4
100%
|
8
100%
|
7
100%
|
12
92.3%
|
13
100%
|
| Title | Number of Participants With a Dose Limiting Toxicities (DLTs) |
|---|---|
| Description | A DLT are defined as adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) occurring during the first two cycles of therapy and related to the study medications (attributions: possible, probable, and definite) while fulfilling one of the following criteria: Any Grade 3 or greater non-hematologic toxicity except asymptomatic grade 3 hypertension, hypomagnesemia, hyponatremia, hypophosphatemia, hypocalcemia, and asymptomatic grade 4 uric acid. A treatment delay of > 2 weeks due to an adverse event (delays due to dental procedures are not included). Grade 4 neutropenia (absolute neutrophil count <500/µL lasting > 5 days. Febrile neutropenia. Grade 3 thrombocytopenia lasting for 7 days or more or thrombocytopenia < 50K/µL requiring platelet transfusion for bleeding. |
| Time Frame | First two cycles of treatment (each cycle is 21 days), approximately 42 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| DLT only pertains to DL1, 2 and 3. Arms A and B did not evaluate for DLT. |
| Arm/Group Title | Ph I Dose Level 1: Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 2: Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 3: Cabozantinib + Docetaxel + Prednisone |
|---|---|---|---|
| Arm/Group Description | Cycle=21 days; Cabozantinib: 20mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 40mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 60mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) |
| Measure Participants | 4 | 8 | 7 |
| Neutropenic fever |
0
0%
|
0
0%
|
1
14.3%
|
| Palmar plantar erythroderma |
0
0%
|
0
0%
|
1
14.3%
|
| Title | Number of Participants Achieving Prostatic-Specific Antigen (PSA) Decline of 30% or 50% From Baseline |
|---|---|
| Description | PSA normal range is 4 ng/ml or lower. Participants with PSA decline of 30% or 50% is the measures for prostate cancer based on conventional reporting metrics. |
| Time Frame | up to 38 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant randomized to Arm A declined to participate before treatment started. |
| Arm/Group Title | Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | Ph II Arm A Docetaxel + Prednisone | Ph II Arm B: Cabozantinib + Docetaxel + Prednisone |
|---|---|---|---|---|---|
| Arm/Group Description | Cycle=21 days; Cabozantinib: 20 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 40 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 60 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg by mouth (PO) twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg by mouth (PO) twice a day (BID); Cabozantinib: 40mg by mouth (PO) everyday (QD) |
| Measure Participants | 3 | 8 | 7 | 12 | 13 |
| Decline in PSA>30% from baseline |
0
0%
|
5
62.5%
|
5
71.4%
|
5
38.5%
|
10
76.9%
|
| Decline in PSA>50% from baseline |
0
0%
|
5
62.5%
|
4
57.1%
|
3
23.1%
|
9
69.2%
|
Adverse Events
| Time Frame | Adverse events were assessed from the date treatment consent signed to date off study, approximately 45 months and 14 days for Arm A; 43 months and 14 days for Arm B; 9 months and 11 days for Dose Level 1; 27 months and 1 day for Dose Level 2; and 11 months and 25 days for Dose Level 3. | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | One participant in Arm/Group A declined to participate before treatment started. | |||||||||
| Arm/Group Title | Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | Ph II Arm A: Docetaxel + Prednisone | Ph II Arm B: Cabozantinib + Docetaxel + Prednisone | |||||
| Arm/Group Description | Cycle=21 days; Cabozantinib: 20 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 40 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Cabozantinib: 60 mg by mouth (PO) everyday (QD); Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg by mouth (PO) twice a day (BID) | Cycle=21 days; Docetaxel: 75 mg/m^2 intravenous (IV) over 60 min on day 1; Prednisone: 5 mg PO twice a day (BID); Cabozantinib: 40 mg by mouth (PO) everyday (QD) | |||||
All Cause Mortality |
||||||||||
| Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | Ph II Arm A: Docetaxel + Prednisone | Ph II Arm B: Cabozantinib + Docetaxel + Prednisone | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | 0/8 (0%) | 2/7 (28.6%) | 0/12 (0%) | 1/13 (7.7%) | |||||
Serious Adverse Events |
||||||||||
| Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | Ph II Arm A: Docetaxel + Prednisone | Ph II Arm B: Cabozantinib + Docetaxel + Prednisone | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 5/8 (62.5%) | 2/7 (28.6%) | 3/12 (25%) | 3/13 (23.1%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anemia | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Heart failure | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Lower gastrointestinal hemorrhage | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Gastric ulcer | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Rectal ulcer | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Oral pain | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| General disorders | ||||||||||
| Sudden death NOS | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Infusion related reaction | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Fever | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Death NOS | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Infections and infestations | ||||||||||
| Anorectal infection | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 |
| Appendicitis | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Lung infection | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Skin infection | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Investigations | ||||||||||
| Febrile neutropenia | 0/4 (0%) | 0 | 2/8 (25%) | 2 | 2/7 (28.6%) | 2 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Neutrophil count decreased | 2/4 (50%) | 4 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Hyperglycemia | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 2 | 0/13 (0%) | 0 |
| Hypoglycemia | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Transient ischemic attacks | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Surgical and medical procedures | ||||||||||
| Thromboembolic event | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||
| Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | Ph II Arm A: Docetaxel + Prednisone | Ph II Arm B: Cabozantinib + Docetaxel + Prednisone | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 8/8 (100%) | 7/7 (100%) | 12/12 (100%) | 13/13 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anemia | 0/4 (0%) | 0 | 3/8 (37.5%) | 11 | 1/7 (14.3%) | 1 | 4/12 (33.3%) | 5 | 1/13 (7.7%) | 1 |
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 3 | 0/13 (0%) | 0 |
| Palpitations | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Sinus tachycardia | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||
| Vertigo | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Eye disorders | ||||||||||
| Watering eyes | 1/4 (25%) | 1 | 1/8 (12.5%) | 1 | 1/7 (14.3%) | 1 | 1/12 (8.3%) | 1 | 2/13 (15.4%) | 2 |
| Blurred vision | 1/4 (25%) | 1 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Periorbital edema | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Bloating | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Constipation | 1/4 (25%) | 1 | 3/8 (37.5%) | 4 | 2/7 (28.6%) | 2 | 2/12 (16.7%) | 2 | 1/13 (7.7%) | 1 |
| Diarrhea | 1/4 (25%) | 3 | 6/8 (75%) | 9 | 2/7 (28.6%) | 3 | 3/12 (25%) | 3 | 5/13 (38.5%) | 7 |
| Duodenal ulcer | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Gastroparesis | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Nausea | 1/4 (25%) | 1 | 5/8 (62.5%) | 8 | 4/7 (57.1%) | 5 | 2/12 (16.7%) | 2 | 4/13 (30.8%) | 4 |
| Proctitis | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Rectal hemorrhage | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Vomiting | 2/4 (50%) | 3 | 4/8 (50%) | 6 | 2/7 (28.6%) | 3 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 |
| Abdominal distension | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Colitis | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 2/13 (15.4%) | 3 |
| Dyspepsia | 2/4 (50%) | 3 | 2/8 (25%) | 2 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Mucositis oral | 1/4 (25%) | 1 | 6/8 (75%) | 11 | 3/7 (42.9%) | 5 | 0/12 (0%) | 0 | 2/13 (15.4%) | 2 |
| Oral dysesthesia | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Oral pain | 0/4 (0%) | 0 | 4/8 (50%) | 4 | 2/7 (28.6%) | 3 | 0/12 (0%) | 0 | 4/13 (30.8%) | 5 |
| Rectal pain | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Rectal perforation | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Rectal ulcer | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Abdominal pain | 1/4 (25%) | 1 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Dry mouth | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Fecal incontinence | 1/4 (25%) | 1 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Flatulence | 1/4 (25%) | 1 | 1/8 (12.5%) | 1 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Gingival pain | 1/4 (25%) | 2 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Gastroesophageal reflux disease | 0/4 (0%) | 0 | 2/8 (25%) | 3 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Toothache | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Gastritis | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| General disorders | ||||||||||
| Chills | 1/4 (25%) | 1 | 1/8 (12.5%) | 1 | 1/7 (14.3%) | 1 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 |
| Fatigue | 2/4 (50%) | 2 | 5/8 (62.5%) | 5 | 2/7 (28.6%) | 3 | 6/12 (50%) | 8 | 3/13 (23.1%) | 3 |
| Gait disturbance | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Infusion related reaction | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Infusion site extravasation | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Malaise | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Pain | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 2/12 (16.7%) | 3 | 1/13 (7.7%) | 1 |
| Fever | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 2/13 (15.4%) | 2 |
| Edema limbs | 0/4 (0%) | 0 | 5/8 (62.5%) | 8 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Infections and infestations | ||||||||||
| Nail infection | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Gum infection | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Upper respiratory infection | 1/4 (25%) | 2 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 2/13 (15.4%) | 2 |
| Urinary tract infection | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Lung infection | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Skin infection | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Mucosal infection | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Fall | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Fracture | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Burn | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Bruising | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Infusion site extravasation | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Investigations | ||||||||||
| Blood bilirubin increased | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| GGT increased | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 2 | 0/13 (0%) | 0 |
| Lipase increased | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 6 | 1/13 (7.7%) | 3 |
| Lymphocyte count decreased | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Platelet count decreased | 1/4 (25%) | 2 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 2/12 (16.7%) | 2 | 0/13 (0%) | 0 |
| Serum amylase increased | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 10 | 1/13 (7.7%) | 5 |
| Weight gain | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 2 | 0/13 (0%) | 0 |
| Weight loss | 0/4 (0%) | 0 | 6/8 (75%) | 10 | 2/7 (28.6%) | 2 | 1/12 (8.3%) | 1 | 2/13 (15.4%) | 3 |
| Alanine aminotransferase increased | 2/4 (50%) | 2 | 2/8 (25%) | 2 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Neutrophil count decreased | 3/4 (75%) | 7 | 7/8 (87.5%) | 16 | 4/7 (57.1%) | 6 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Aspartate aminotransferase increased | 1/4 (25%) | 2 | 2/8 (25%) | 2 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Creatinine increased | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| White blood cell decreased | 1/4 (25%) | 4 | 3/8 (37.5%) | 8 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Anorexia | 0/4 (0%) | 0 | 4/8 (50%) | 5 | 3/7 (42.9%) | 3 | 3/12 (25%) | 3 | 5/13 (38.5%) | 5 |
| Dehydration | 0/4 (0%) | 0 | 3/8 (37.5%) | 3 | 2/7 (28.6%) | 3 | 1/12 (8.3%) | 1 | 2/13 (15.4%) | 2 |
| Hypercalcemia | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Hyperglycemia | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Hypophosphatemia | 2/4 (50%) | 12 | 5/8 (62.5%) | 6 | 1/7 (14.3%) | 9 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 2 |
| Hypocalcemia | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Hypokalemia | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Hypomagnesemia | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Hypoalbuminemia | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Hypoglycemia | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Hyponatremia | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 2/12 (16.7%) | 2 | 1/13 (7.7%) | 1 |
| Back pain | 1/4 (25%) | 1 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 2/12 (16.7%) | 2 | 2/13 (15.4%) | 2 |
| Flank pain | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Generalized muscle weakness | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 2/12 (16.7%) | 2 | 0/13 (0%) | 0 |
| Muscle weakness lower limb | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Myalgia | 0/4 (0%) | 0 | 4/8 (50%) | 4 | 0/7 (0%) | 0 | 2/12 (16.7%) | 2 | 4/13 (30.8%) | 4 |
| Chest wall pain | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Musculoskeletal and connective tissue disorder - Other, specify | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Neck edema | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Osteonecrosis of jaw | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Bone pain | 0/4 (0%) | 0 | 1/8 (12.5%) | 2 | 2/7 (28.6%) | 4 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Dizziness | 1/4 (25%) | 1 | 2/8 (25%) | 2 | 3/7 (42.9%) | 4 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Dysgeusia | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 7/12 (58.3%) | 7 | 8/13 (61.5%) | 8 |
| Paresthesia | 0/4 (0%) | 0 | 4/8 (50%) | 4 | 2/7 (28.6%) | 6 | 4/12 (33.3%) | 4 | 0/13 (0%) | 0 |
| Peripheral sensory neuropathy | 1/4 (25%) | 1 | 2/8 (25%) | 2 | 3/7 (42.9%) | 3 | 2/12 (16.7%) | 2 | 0/13 (0%) | 0 |
| Headache | 1/4 (25%) | 1 | 1/8 (12.5%) | 2 | 2/7 (28.6%) | 2 | 0/12 (0%) | 0 | 3/13 (23.1%) | 3 |
| Nervous system disorders - Other, neuropathy | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Presyncope | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Syncope | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Movements involuntary | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Tremor | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Psychiatric disorders | ||||||||||
| Confusion | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Insomnia | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 2/7 (28.6%) | 2 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Renal and urinary disorders | ||||||||||
| Urinary incontinence | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Urinary tract obstruction | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Urinary tract pain | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||
| Testicular pain | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Genital edema | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Gynecomastia | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Pelvic pain | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Allergic rhinitis | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Hoarseness | 0/4 (0%) | 0 | 2/8 (25%) | 2 | 1/7 (14.3%) | 1 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 |
| Postnasal drip | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Bronchial obstruction | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Cough | 1/4 (25%) | 1 | 1/8 (12.5%) | 2 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 3/13 (23.1%) | 3 |
| Dyspnea | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 2/7 (28.6%) | 2 | 0/12 (0%) | 0 | 2/13 (15.4%) | 2 |
| Epistaxis | 1/4 (25%) | 1 | 6/8 (75%) | 7 | 3/7 (42.9%) | 3 | 0/12 (0%) | 0 | 8/13 (61.5%) | 8 |
| Nasal congestion | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Productive cough | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Voice alteration | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Pleuritic pain | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Sore throat | 1/4 (25%) | 1 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Alopecia | 2/4 (50%) | 2 | 4/8 (50%) | 5 | 2/7 (28.6%) | 2 | 3/12 (25%) | 3 | 7/13 (53.8%) | 7 |
| Nail discoloration | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 1/12 (8.3%) | 1 | 3/13 (23.1%) | 3 |
| Nail loss | 1/4 (25%) | 1 | 3/8 (37.5%) | 3 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 2/13 (15.4%) | 2 |
| Pruritus | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Nail ridging | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Palmar-plantar erythrodysesthesia syndrome | 2/4 (50%) | 2 | 7/8 (87.5%) | 26 | 3/7 (42.9%) | 4 | 0/12 (0%) | 0 | 6/13 (46.2%) | 8 |
| Skin and subcutaneous tissue disorders - Other, skin discoloration | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Skin hypopigmentation | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 4/7 (57.1%) | 6 | 0/12 (0%) | 0 | 4/13 (30.8%) | 14 |
| Scalp pain | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Skin and subcutaneous tissue disorders - Other, dermatitis-eye | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Skin ulceration | 1/4 (25%) | 1 | 1/8 (12.5%) | 4 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Dry skin | 1/4 (25%) | 1 | 2/8 (25%) | 2 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Papulopustular rash | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Purpura | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Rash maculo-papular | 0/4 (0%) | 0 | 2/8 (25%) | 2 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Skin and subcutaneous tissue disorders - Other, petechiae | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Skin atrophy | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Skin hyperpigmentation | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Pain of skin | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 4 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Rash acneiform | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 2/7 (28.6%) | 2 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Skin and subcutaneous tissue disorders - Other, R. thigh lesion | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Skin and subcutaneous tissue disorders - Other, dermatitis-hand | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Vascular disorders | ||||||||||
| Thromboembolic event | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 2/7 (28.6%) | 2 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Vascular disorders - Other, peripheral vascular disease | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 |
| Flushing | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Hypotension | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 |
| Hypertension | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 2/7 (28.6%) | 2 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Hypotension | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
| Vascular disorders - Other, vasculopathy | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. William Dahut |
|---|---|
| Organization | National Cancer Institute |
| Phone | 240-760-6070 |
| william_dahut@nih.gov |
- 120204
- 12-C-0204