PD 0332991 and Cetuximab in Patients With Incurable SCCHN
Sponsor
Washington University School of Medicine (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02101034
Collaborator
Pfizer (Industry)
96
5
5
129.7
19.2
0.1
Study Details
Study Description
Brief Summary
The purpose of this Phase I/II study is to define the maximum tolerated dose of PD 0332991 given with cetuximab and evaluated the side effects of the combination.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
96 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I/II Trial of the Addition of PD 0332991 to Cetuximab in Patients With Incurable SCCHN
Actual Study Start Date
:
Jun 17, 2014
Actual Primary Completion Date
:
Jun 8, 2020
Anticipated Study Completion Date
:
Apr 9, 2025
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase I: Dose Level 1 PD 0332991 will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
Biological: Cetuximab
Other Names:
Drug: PD 0332991
Other Names:
|
| Experimental: Phase I: Dose Level 2 PD 0332991 will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
Biological: Cetuximab
Other Names:
Drug: PD 0332991
Other Names:
|
| Experimental: Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN PD 0332991 will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
Biological: Cetuximab
Other Names:
Drug: PD 0332991
Other Names:
|
| Experimental: Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN PD 0332991 will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
Biological: Cetuximab
Other Names:
Drug: PD 0332991
Other Names:
|
| Experimental: Phase II Arm 3: PD 0332991 will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
Biological: Cetuximab
Other Names:
Drug: PD 0332991
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase I - Maximum Tolerated Dose (MTD) [6 months (estimated completion of Phase I)]
MTD is the dose level (DL) immediately below the DL at which 2 patients of a cohort experience dose limiting toxicity (DLT) in the 1st cycle (DLTs) Hematologic DLT is any of the below that occur during the 1st cycle that are possibly, probably, or definitely related to the treatment grade 4 neutropenia ≥7 days grade 4 infection with grade 3/4 neutropenia grade 4 thrombocytopenia with life-threatening bleeding treatment held for >14 days due to hematologic toxicity febrile neutropenia with temperature >=38.5°C Non-hematologic DLT is any possibly, probably, or definitely related grade 3 or 4 non-hematologic toxicity that occurs during the 1st except for suboptimally treated grade 3 or 4 nausea, vomiting, diarrhea, anorexia, or lymphopenia grade 3 metabolic abnormalities (limited to potassium, magnesium, and calcium) any hypersensitivity/infusion reaction or acneiform rash due to cetuximab treatment held for >14 days due to non-hematologic toxicity
- Phase II: Efficacy as Measured by Overall Response Rate [End of treatment (estimated to be 12 months)]
Tumor measurements will be collected at baseline, end of every even numbered cycles, and end of treatment. Measured by overall response rate (ORR=CR+PR) defined by RECIST criteria Best overall response is the best response recorded from the start of treatment until disease progression/recurrence Complete Response (CR) is defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR) is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters
Secondary Outcome Measures
- Phase I: Most Frequent Adverse Events [Up to 30 days following completion of treatment (estimated to be 13 months)]
Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- Phase II: PD 0332991 Related Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events [Up to 30 days following completion of treatment (estimated to be 13 months)]
Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- Phase II: Cetuximab Related Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events [Up to 30 days following completion of treatment (estimated to be 13 months)]
Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- Phase II: Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events [Up to 30 days following completion of treatment (estimated to be 13 months)]
Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- Phase II: Progression Free Survival (PFS) [Up to 5 years]
Participants will be followed every 2 months for 5 years or until death, whichever occurs first. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
- Phase II: Overall Survival (OS) [Up to 5 years]
Participants will be followed every 2 months for 5 years or until death, whichever occurs first. Overall survival is measured from time of diagnosis to time of death.
- Phase II: Duration of Response [Completion of treatment (estimated to be 12 months)]
Duration of overall response is measured from the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck.
-
Disease must be considered incurable. Incurable is defined as metastatic disease or a local or regional recurrence in a previously irradiated site that is unresectable (or patient declines resection).
-
Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with CT scan, as ≥20 mm by chest x-ray, or ≥10 mm with calipers by clinical exam. (Phase I only: patients without measurable disease by RECIST 1.1 criteria but with evaluable disease by imaging or physical exam will be eligible as well.)
-
Phase I only: any (or no) prior therapy for metastatic disease is allowed, including cetuximab. If a patient has not received prior standard therapy, s/he must have been offered and refused prior standard therapy.
-
Phase II only:
-
Arm 1: disease progression after at least one cycle of prior treatment with cisplatin or carboplatin for incurable disease. Prior treatment with cetuximab for incurable disease is not permitted.
-
Arms 2 and 3: disease progression after at least one cycle of treatment with cetuximab for incurable disease.
-
Phase II only: at least one line of prior therapy for incurable disease.
-
Phase II only:
-
Arms1 and 2: disease must be determined to be HPV-unrelated. HPV-unrelated SCCHN is defined as either p16-negative OPSCC or non-OPSCC (larynx, hypopharynx, oral cavity) or p16-negative unknown primary SCC presenting with a level 2 or 3 neck node. p16 will be assessed by IHC; a specimen showing any staining will be considered p16-positive.
-
Arm 3: disease must be HPV-related SCCHN (defined as OPSCC or unknown primary presenting with a neck mass that is either p16 positive or HPV ISH or PCR positive).
-
Minimum of 14 days elapsed since the end of any prior therapy.
-
At least 18 years of age.
-
Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion)
-
ECOG performance status ≤ 2
-
Adequate bone marrow and organ function as defined below:
-
Absolute neutrophil count ≥ 1,500 mm3
-
Platelets ≥ 100,000 mm3
-
Hemoglobin > 9 g/dL
-
Total bilirubin ≤ 1.5 x IULN except in the case of patients with Gilbert's disease
-
AST (SGOT) and ALT (SGPT) ≤ 2.5 x IULN for patients without liver metastases and ≤ 5.0 x IULN for patients with liver metastases
-
Alkaline phosphatase ≤ 2.5 x IULN for patients without bone metastases and ≤ 5.0 x IULN for patients with bone metastases
-
Serum creatinine ≤ 1.5 x IULN OR calculated creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
-
Baseline corrected QT interval (QTc) < 480 ms.
-
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
-
Available archival tumor tissue for the proposed correlative studies.
-
Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
-
Phase II, Arm 1 only: prior treatment with cetuximab.
-
Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion)
-
A history of other malignancy ≤ 1 year previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only, carcinoma in situ of the cervix, or synchronous H&N primaries.
-
Currently receiving any other investigational agents.
-
Patient must not have a history of or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, except for individuals who have had previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications (with the exception of Keppra) for 1 month prior to first dose of PD 0332991.
-
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991, cetuximab, or other agents used in the study.
-
Treated within the last 7 days prior to Day 1 of protocol therapy with:
-
Food or drugs that are known to be CYP3A4 inhibitors (e.g. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, telithromycin, indinavir, ritonavir, nelfinavir, atazanavir, amprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort).
-
Drugs that are known to prolong the QT interval.
-
Drugs that are proton pump inhibitors.
-
Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia)
-
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
-
Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 28 days of study entry. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraceptive during the period of the trial and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator or a designated associate.
-
Phase I and Arm 1 of Phase II: Known HIV-positivity and on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with PD 0332991. 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.
Arms 2 and 3 of Phase II: patients with HIV infection and antiretroviral therapy are not excluded, as there are no pharmacokinetic tests being performed.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Winship Cancer Institute of Emory University | Atlanta | Georgia | United States | 30322 |
| 2 | University of Kansas | Westwood | Kansas | United States | 66205 |
| 3 | University of Michigan Health System | Ann Arbor | Michigan | United States | 48109 |
| 4 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 5 | University of Rochester Medical Center | Rochester | New York | United States | 14642 |
Sponsors and Collaborators
- Washington University School of Medicine
- Pfizer
Investigators
- Principal Investigator: Douglas Adkins, M.D., Washington University School of Medicine
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT02101034
Other Study ID Numbers:
- 201404139
First Posted:
Apr 1, 2014
Last Update Posted:
May 25, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Phase I: Dose Level 1 | Phase I: Dose Level 2 | Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN | Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN | Phase II Arm 3: |
|---|---|---|---|---|---|
| Arm/Group Description | PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
| Period Title: Overall Study | |||||
| STARTED | 3 | 6 | 31 | 32 | 24 |
| COMPLETED | 3 | 6 | 30 | 32 | 24 |
| NOT COMPLETED | 0 | 0 | 1 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Phase I: Dose Level 1 | Phase I: Dose Level 2 | Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN | Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN | Phase II Arm 3: | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | Total of all reporting groups |
| Overall Participants | 3 | 6 | 31 | 32 | 24 | 96 |
| Age (years) [Median (Full Range) ] | ||||||
| Median (Full Range) [years] |
62
|
61
|
64
|
64
|
66
|
63
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
0
0%
|
2
33.3%
|
7
22.6%
|
11
34.4%
|
2
8.3%
|
22
22.9%
|
| Male |
3
100%
|
4
66.7%
|
24
77.4%
|
21
65.6%
|
22
91.7%
|
74
77.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
3.2%
|
1
3.1%
|
0
0%
|
2
2.1%
|
| Not Hispanic or Latino |
3
100%
|
6
100%
|
30
96.8%
|
30
93.8%
|
23
95.8%
|
92
95.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
1
3.1%
|
1
4.2%
|
2
2.1%
|
| 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%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
1
1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
2
33.3%
|
7
22.6%
|
7
21.9%
|
0
0%
|
16
16.7%
|
| White |
3
100%
|
3
50%
|
23
74.2%
|
24
75%
|
24
100%
|
77
80.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
3.2%
|
1
3.1%
|
0
0%
|
2
2.1%
|
| Region of Enrollment (participants) [Number] | ||||||
| United States |
3
100%
|
6
100%
|
31
100%
|
32
100%
|
24
100%
|
96
100%
|
Outcome Measures
| Title | Phase I - Maximum Tolerated Dose (MTD) |
|---|---|
| Description | MTD is the dose level (DL) immediately below the DL at which 2 patients of a cohort experience dose limiting toxicity (DLT) in the 1st cycle (DLTs) Hematologic DLT is any of the below that occur during the 1st cycle that are possibly, probably, or definitely related to the treatment grade 4 neutropenia ≥7 days grade 4 infection with grade 3/4 neutropenia grade 4 thrombocytopenia with life-threatening bleeding treatment held for >14 days due to hematologic toxicity febrile neutropenia with temperature >=38.5°C Non-hematologic DLT is any possibly, probably, or definitely related grade 3 or 4 non-hematologic toxicity that occurs during the 1st except for suboptimally treated grade 3 or 4 nausea, vomiting, diarrhea, anorexia, or lymphopenia grade 3 metabolic abnormalities (limited to potassium, magnesium, and calcium) any hypersensitivity/infusion reaction or acneiform rash due to cetuximab treatment held for >14 days due to non-hematologic toxicity |
| Time Frame | 6 months (estimated completion of Phase I) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only Phase I participants were evaluable for this outcome measure. |
| Arm/Group Title | Phase I: Dose Level 1 and Dose Level 2 | Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN | Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN | Phase II Arm 3: |
|---|---|---|---|---|
| Arm/Group Description | PD 0332991 will be administered on Days 1 through 21 of each 28 day cycle. Dose Level 1 PD 0332991 100 mg per day Dose Level 2 PD 0332991 125 mg per day Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
| Measure Participants | 9 | 0 | 0 | 0 |
| Number [mg] |
NA
|
| Title | Phase II: Efficacy as Measured by Overall Response Rate |
|---|---|
| Description | Tumor measurements will be collected at baseline, end of every even numbered cycles, and end of treatment. Measured by overall response rate (ORR=CR+PR) defined by RECIST criteria Best overall response is the best response recorded from the start of treatment until disease progression/recurrence Complete Response (CR) is defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR) is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters |
| Time Frame | End of treatment (estimated to be 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase I participants were excluded from this outcome measure. 2 participants in Phase II Arm 1 were not evaluable due to early death and inability to measure the target lesion on the post-treatment non-contrast CT scan. 5 participants in Phase II Arm 2 were not evaluable due to comorbidity-related death (N=2), patient withdrawal (N=2), and non-treatment related adverse event (N=1). |
| Arm/Group Title | Phase I: Dose Level 1 | Phase I: Dose Level 2 | Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN | Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN | Phase II Arm 3: |
|---|---|---|---|---|---|
| Arm/Group Description | PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
| Measure Participants | 0 | 0 | 28 | 27 | 24 |
| Count of Participants [Participants] |
11
366.7%
|
5
83.3%
|
1
3.2%
|
| Title | Phase I: Most Frequent Adverse Events |
|---|---|
| Description | Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
| Time Frame | Up to 30 days following completion of treatment (estimated to be 13 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase I: Dose Level 1 | Phase I: Dose Level 2 |
|---|---|---|
| Arm/Group Description | PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
| Measure Participants | 3 | 6 |
| Grades 1-2 Neutropenia |
1
33.3%
|
2
33.3%
|
| Grade 3 Neutropenia |
1
33.3%
|
2
33.3%
|
| Grades 1-2 Anemia |
2
66.7%
|
6
100%
|
| Grade 3 Anemia |
1
33.3%
|
0
0%
|
| Grades 1-2 Thrombocytopenia |
1
33.3%
|
3
50%
|
| Grade 3 Thrombocytopenia |
1
33.3%
|
0
0%
|
| Grades 1-2 Fatigue |
2
66.7%
|
3
50%
|
| Grade 3 Fatigue |
0
0%
|
0
0%
|
| Grades 1-2 Nausea |
0
0%
|
2
33.3%
|
| Grade 3 Nausea |
0
0%
|
0
0%
|
| Grade 1-2 Vomiting |
0
0%
|
1
16.7%
|
| Grade 3 Vomiting |
0
0%
|
0
0%
|
| Grade 1-2 Diarrhea |
1
33.3%
|
1
16.7%
|
| Grade 3 Diarrhea |
0
0%
|
0
0%
|
| Grade 1-2 Infusion Reaction |
0
0%
|
1
16.7%
|
| Grade 3 Infusion Reaction |
0
0%
|
0
0%
|
| Grade 1-2 Acneiform Rash |
2
66.7%
|
5
83.3%
|
| Grade 3 Acneiform Rash |
0
0%
|
0
0%
|
| Grade 1-2 Hypomagnesemia |
1
33.3%
|
2
33.3%
|
| Grade 3 Hypomagnesemia |
1
33.3%
|
0
0%
|
| Title | Phase II: PD 0332991 Related Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events |
|---|---|
| Description | Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
| Time Frame | Up to 30 days following completion of treatment (estimated to be 13 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All arms of the Phase II Portion of the study were combined for this outcome measure as the treatment received was the same for each arm. |
| Arm/Group Title | Phase II Arm 1, Arm 2, and Arm 3 |
|---|---|
| Arm/Group Description | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
| Measure Participants | 86 |
| Grades 1-2 platelet count decreased |
50
1666.7%
|
| Grades 3-5 platelet count decreased |
11
366.7%
|
| Grades 1-2 neutrophil count decreased |
28
933.3%
|
| Grades 3-5 neutrophil count decreased |
29
966.7%
|
| Grades 1-2 white blood cell count decreased |
43
1433.3%
|
| Grades 3-5 white blood cell count decreased |
24
800%
|
| Grades 1-2 electrocardiogram QT corrected interval prolonged |
6
200%
|
| Grades 3-5 electrocardiogram QT corrected interval prolonged |
1
33.3%
|
| Title | Phase II: Cetuximab Related Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events |
|---|---|
| Description | Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
| Time Frame | Up to 30 days following completion of treatment (estimated to be 13 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All arms of the Phase II Portion of the study were combined for this outcome measure as the treatment received was the same for each arm. |
| Arm/Group Title | Phase II Arm 1, Arm 2, and Arm 3 |
|---|---|
| Arm/Group Description | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
| Measure Participants | 86 |
| Grades 1-2 acneiform rash |
60
2000%
|
| Grades 3-5 acneiform rash |
0
0%
|
| Grades 1-2 hypomagnesemia |
23
766.7%
|
| Grades 3-5 hypomagnesemia |
1
33.3%
|
| Title | Phase II: Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events |
|---|---|
| Description | Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
| Time Frame | Up to 30 days following completion of treatment (estimated to be 13 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All arms of the Phase II Portion of the study were combined for this outcome measure as the treatment received was the same for each arm. |
| Arm/Group Title | Phase II: Arm 1, Arm 2, and Arm 3 |
|---|---|
| Arm/Group Description | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
| Measure Participants | 86 |
| Grades 1-2 fatigue |
48
1600%
|
| Grades 3-5 fatigue |
8
266.7%
|
| Grades 1-2 hypoalbuminemia |
37
1233.3%
|
| Grades 3-5 hypoalbuminemia |
3
100%
|
| Grades 1-2 anemia |
44
1466.7%
|
| Grades 3-5 anemia |
20
666.7%
|
| Grades 1-2 hyponatremia |
30
1000%
|
| Grades 3-5 hyponatremia |
1
33.3%
|
| Grades 1-2 hypertension |
24
800%
|
| Grades 3-5 hypertension |
3
100%
|
| Grades 1-2 nausea |
30
1000%
|
| Grades 3-5 nausea |
3
100%
|
| Grades 1-2 dysphagia |
30
1000%
|
| Grades 3-5 dysphagia |
6
200%
|
| Grades 1-2 dyspnea |
29
966.7%
|
| Grades 3-5 dyspnea |
5
166.7%
|
| Grades 1-2 hypocalcemia |
19
633.3%
|
| Grades 3-5 hypocalcemia |
4
133.3%
|
| Grades 1-2 lymphocyte count decreased |
19
633.3%
|
| Grades 3-5 lymphocyte count decreased |
22
733.3%
|
| Grades 1-2 diarrhea |
21
700%
|
| Grades 3-5 diarrhea |
2
66.7%
|
| Grades 1-2 weight loss |
24
800%
|
| Grades 3-5 weight loss |
6
200%
|
| Grades 1-2 AST increased |
22
733.3%
|
| Grades 3-5 AST increased |
0
0%
|
| Grades 1-2 tumor pain |
18
600%
|
| Grades 3-5 tumor pain |
3
100%
|
| Grades 1-2 constipation |
15
500%
|
| Grades 3-5 constipation |
0
0%
|
| Grades 1-2 cough |
21
700%
|
| Grades 3-5 cough |
0
0%
|
| Grades 1-2 anorexia |
21
700%
|
| Grades 3-5 anorexia |
3
100%
|
| Grades 1-2 vomiting |
17
566.7%
|
| Grades 3-5 vomiting |
2
66.7%
|
| Grades 1-2 dry mouth |
13
433.3%
|
| Grades 3-5 dry mouth |
0
0%
|
| Grades 1-2 sinus tachycardia |
12
400%
|
| Grades 3-5 sinus tachycardia |
0
0%
|
| Grades 1-2 alkaline phosphatase increased |
12
400%
|
| Grades 3-5 alkaline phosphatase increased |
0
0%
|
| Grades 1-2 hypokalemia |
12
400%
|
| Grades 3-4 hypokalemia |
11
366.7%
|
| Grades 1-2 hyperglycemia |
11
366.7%
|
| Grades 3-5 hyperglycemia |
11
366.7%
|
| Grades 1-2 hypernatremia |
16
533.3%
|
| Grades 3-5 hypernatremia |
1
33.3%
|
| Grades 1-2 fever |
12
400%
|
| Grades 3-5 fever |
1
33.3%
|
| Grades 1-2 dizziness |
9
300%
|
| Grades 3-5 dizziness |
2
66.7%
|
| Grades 1-2 hypercalcemia |
9
300%
|
| Grades 3-5 hypercalcemia |
1
33.3%
|
| Grades 1-2 dry skin |
18
600%
|
| Grades 3-5 dry skin |
1
33.3%
|
| Grades 1-2 dehydration |
8
266.7%
|
| Grades 3-5 dehydration |
2
66.7%
|
| Grades 1-2 hypotension |
8
266.7%
|
| Grades 3-5 hypotension |
1
33.3%
|
| Grades 1-2 creatinine increased |
12
400%
|
| Grades 3-5 creatinine increased |
1
33.3%
|
| Grades 1-2 trismus |
7
233.3%
|
| Grades 3-5 trismus |
1
33.3%
|
| Grades 1-2 elevated INR |
6
200%
|
| Grades 3-5 elevated INR |
1
33.3%
|
| Grades 1-2 dysarthria |
5
166.7%
|
| Grades 3-5 dysarthria |
1
33.3%
|
| Grades 1-2 hypophosphatemia |
3
100%
|
| Grades 3-5 hypophosphatemia |
8
266.7%
|
| Grades 1-2 lung infection |
1
33.3%
|
| Grades 3-5 lung infection |
8
266.7%
|
| Grades 1-2 febrile neutropenia |
0
0%
|
| Grades 3-5 febrile neutropenia |
2
66.7%
|
| Grade 1-2 abdominal pain |
0
0%
|
| Grades 3-5 abdominal pain |
2
66.7%
|
| Grades 1-2 colitis |
0
0%
|
| Grades 3-5 colitis |
1
33.3%
|
| Grades 1-2 tumor hemorrhage |
0
0%
|
| Grades 3-5 tumor hemorrhage |
2
66.7%
|
| Grades 1-2 hematuria |
0
0%
|
| Grades 3-5 hematuria |
1
33.3%
|
| Grades 1-2 duodenal ulcer |
0
0%
|
| Grades 3-5 duodenal ulcer |
1
33.3%
|
| Grades 1-2 esophageal fistula |
0
0%
|
| Grades 3-5 esophageal fistula |
1
33.3%
|
| Grades 1-2 oral cavity fistula |
0
0%
|
| Grades 3-5 oral cavity fistula |
1
33.3%
|
| Grades 1-2 sepsis |
0
0%
|
| Grades 3-5 sepsis |
7
233.3%
|
| Grades 1-2 duodenal perforation |
0
0%
|
| Grades 3-5 duodenal perforation |
1
33.3%
|
| Grades 1-2 skin infection |
0
0%
|
| Grades 3-5 skin infection |
4
133.3%
|
| Grades 1-2 tracheitis |
0
0%
|
| Grades 3-5 tracheitis |
1
33.3%
|
| Grades 1-2 aspiration |
0
0%
|
| Grades 3-5 aspiration |
1
33.3%
|
| Grades 1-2 pleural effusion |
0
0%
|
| Grades 3-5 pleural effusion |
1
33.3%
|
| Grades 1-2 pneumothorax |
0
0%
|
| Grades 3-5 pneumothorax |
1
33.3%
|
| Grades 1-2 catheter-related infection |
0
0%
|
| Grades 3-5 catheter-related infection |
1
33.3%
|
| Grades 1-2 jejunal obstruction |
0
0%
|
| Grades 3-5 jejunal obstruction |
1
33.3%
|
| Grades 1-2 mucositis oral |
4
133.3%
|
| Grades 3-5 mucositis oral |
2
66.7%
|
| Grades 1-2 oral hemorrhage |
0
0%
|
| Grades 3-5 oral hemorrhage |
1
33.3%
|
| Grade 5 death, not otherwise specified |
3
100%
|
| Grades 1-2 infusion-related reaction |
0
0%
|
| Grades 3-5 infusion-related reaction |
1
33.3%
|
| Grades 1-2 urinary tract infection |
0
0%
|
| Grades 3-5 urinary tract infection |
2
66.7%
|
| Grades 1-2 respiratory failure |
0
0%
|
| Grades 3-5 respiratory failure |
2
66.7%
|
| Grades 1-2 hypothyroidism |
5
166.7%
|
| Grades 3-5 hypothyroidism |
0
0%
|
| Grades 1-2 edema face |
2
66.7%
|
| Grades 3-5 edema face |
1
33.3%
|
| Grades 1-2 non-cardiac chest pain |
2
66.7%
|
| Grades 3-5 non-cardiac chest pain |
1
33.3%
|
| Grades 1-2 pancreatitis |
0
0%
|
| Grades 3-5 pancreatitis |
1
33.3%
|
| Grades 1-2 encephalopathy |
0
0%
|
| Grades 3-5 encephalopathy |
1
33.3%
|
| Grades 1-2 acute kidney injury |
0
0%
|
| Grades 3-5 acute kidney injury |
1
33.3%
|
| Grades 1-2 proteinuria |
0
0%
|
| Grades 3-5 proteinuria |
1
33.3%
|
| Grades 1-2 thromboembolic event |
0
0%
|
| Grades 3-5 thromboembolic event |
1
33.3%
|
| Title | Phase II: Progression Free Survival (PFS) |
|---|---|
| Description | Participants will be followed every 2 months for 5 years or until death, whichever occurs first. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. |
| Time Frame | Up to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Phase II: Overall Survival (OS) |
|---|---|
| Description | Participants will be followed every 2 months for 5 years or until death, whichever occurs first. Overall survival is measured from time of diagnosis to time of death. |
| Time Frame | Up to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Phase II: Duration of Response |
|---|---|
| Description | Duration of overall response is measured from the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented. |
| Time Frame | Completion of treatment (estimated to be 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase I participants were not evaluable for this outcome measure. |
| Arm/Group Title | Phase I: Dose Level 1 | Phase I: Dose Level 2 | Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN | Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN | Phase II Arm 3: |
|---|---|---|---|---|---|
| Arm/Group Description | PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. |
| Measure Participants | 0 | 0 | 11 | 5 | 1 |
| Median (Inter-Quartile Range) [months] |
4.0
|
6.0
|
4.0
|
Adverse Events
| Time Frame | Adverse events were followed from start of study treatment until 30 days following the last day of study treatment. | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Phase I: Dose Level 1 | Phase I: Dose Level 2 | Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN | Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN | Phase II Arm 3: | |||||
| Arm/Group Description | PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study. | |||||
All Cause Mortality |
||||||||||
| Phase I: Dose Level 1 | Phase I: Dose Level 2 | Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN | Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN | Phase II Arm 3: | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 6/6 (100%) | 26/30 (86.7%) | 19/32 (59.4%) | 15/24 (62.5%) | |||||
Serious Adverse Events |
||||||||||
| Phase I: Dose Level 1 | Phase I: Dose Level 2 | Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN | Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN | Phase II Arm 3: | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 4/6 (66.7%) | 21/30 (70%) | 16/32 (50%) | 9/24 (37.5%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Febrile neutropenia | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 1/3 (33.3%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Ascites | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Diarrhea | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Duodenal obstruction | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Duodenal perforation | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Duodenal ulcer | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Dysphagia | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 1/24 (4.2%) | |||||
| Esophageal fistula | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Jejunal obstruction | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Nausa | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Oral cavity fistula | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Oral hemorrhage | 0/3 (0%) | 1/6 (16.7%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Pancreatitis | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Vomiting | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| General disorders | ||||||||||
| Death NOS | 0/3 (0%) | 0/6 (0%) | 3/30 (10%) | 0/32 (0%) | 0/24 (0%) | |||||
| Edema limbs | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Failure to thrive | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Fall | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 2/32 (6.3%) | 0/24 (0%) | |||||
| Fatigue | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Fever | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 2/24 (8.3%) | |||||
| Infusion related reaction | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Immune system disorders | ||||||||||
| Allergic reaction | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Infections and infestations | ||||||||||
| Catheter related infection | 0/3 (0%) | 1/6 (16.7%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Influenza | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Lung infection | 0/3 (0%) | 1/6 (16.7%) | 8/30 (26.7%) | 3/32 (9.4%) | 3/24 (12.5%) | |||||
| Meningitis | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Sepsis | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 3/32 (9.4%) | 1/24 (4.2%) | |||||
| Skin infection | 0/3 (0%) | 1/6 (16.7%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Tracheitis | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Upper respiratory infection | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Urinary tract infection | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Wound infection | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Hip fracture | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Intestinal stoma leak | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Anorexia | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Hypercalcemia | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Hypokalemia | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Facial muscle weakness | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Tumor pain | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 2/32 (6.3%) | 0/24 (0%) | |||||
| Nervous system disorders | ||||||||||
| Encephalopathy | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Psychiatric disorders | ||||||||||
| Confusion | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Aspiration | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Dyspnea | 1/3 (33.3%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 1/24 (4.2%) | |||||
| Hypoxia | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Laryngeal hemorrhage | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Pharyngeal hemorrhage | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Pneumothorax | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Respiratory failure | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Vascular disorders | ||||||||||
| Thromboembolic event | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Phase I: Dose Level 1 | Phase I: Dose Level 2 | Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN | Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN | Phase II Arm 3: | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 6/6 (100%) | 30/30 (100%) | 32/32 (100%) | 24/24 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anemia | 3/3 (100%) | 6/6 (100%) | 30/30 (100%) | 24/32 (75%) | 17/24 (70.8%) | |||||
| Febrile neutropenia | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Constrictive pericarditis | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Sinus bradycardia | 0/3 (0%) | 0/6 (0%) | 3/30 (10%) | 1/32 (3.1%) | 2/24 (8.3%) | |||||
| Sinus tachycardia | 0/3 (0%) | 2/6 (33.3%) | 20/30 (66.7%) | 12/32 (37.5%) | 4/24 (16.7%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Ear pain | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Hearing imparied | 0/3 (0%) | 0/6 (0%) | 5/30 (16.7%) | 1/32 (3.1%) | 2/24 (8.3%) | |||||
| Otorrhea | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Tinnitus | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 2/24 (8.3%) | |||||
| Vertigo | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Endocrine disorders | ||||||||||
| Hyperthyroidism | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Hypoparathyroidism | 0/3 (0%) | 0/6 (0%) | 5/30 (16.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Hypothrydodism | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 4/32 (12.5%) | 5/24 (20.8%) | |||||
| Eye disorders | ||||||||||
| Blurred vision | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Conjuctivitis | 0/3 (0%) | 0/6 (0%) | 3/30 (10%) | 2/32 (6.3%) | 0/24 (0%) | |||||
| Dry eye | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Eye discomfort | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Melanocytic nevus | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 3/32 (9.4%) | 4/24 (16.7%) | |||||
| Anal hemorrhage | 1/3 (33.3%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Ascites | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Colitis | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Constipation | 1/3 (33.3%) | 1/6 (16.7%) | 9/30 (30%) | 6/32 (18.8%) | 3/24 (12.5%) | |||||
| Diarrhea | 1/3 (33.3%) | 1/6 (16.7%) | 12/30 (40%) | 10/32 (31.3%) | 3/24 (12.5%) | |||||
| Dry mouth | 1/3 (33.3%) | 3/6 (50%) | 18/30 (60%) | 13/32 (40.6%) | 10/24 (41.7%) | |||||
| Duodenal ulcer | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Dyspepsia | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 3/32 (9.4%) | 1/24 (4.2%) | |||||
| Dysphagia | 0/3 (0%) | 3/6 (50%) | 19/30 (63.3%) | 13/32 (40.6%) | 8/24 (33.3%) | |||||
| Esophageal fistula | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Fecal incontinence | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Gastroesophageal reflux disease | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 2/32 (6.3%) | 5/24 (20.8%) | |||||
| Hemorrhoids | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Hypersalivation | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 2/32 (6.3%) | 0/24 (0%) | |||||
| Mouth sores | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Mucositis oral | 1/3 (33.3%) | 0/6 (0%) | 10/30 (33.3%) | 5/32 (15.6%) | 5/24 (20.8%) | |||||
| Nausea | 0/3 (0%) | 2/6 (33.3%) | 10/30 (33.3%) | 18/32 (56.3%) | 7/24 (29.2%) | |||||
| Odynophagia | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Oral bleeding | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 2/32 (6.3%) | 0/24 (0%) | |||||
| Oral cavity fistula | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Oral dysesthesia | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 2/24 (8.3%) | |||||
| Oral hemorrhage | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Oral pain | 2/3 (66.7%) | 2/6 (33.3%) | 1/30 (3.3%) | 2/32 (6.3%) | 3/24 (12.5%) | |||||
| Rectal bleeding | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Sore tongue | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Vomiting | 0/3 (0%) | 1/6 (16.7%) | 5/30 (16.7%) | 10/32 (31.3%) | 3/24 (12.5%) | |||||
| General disorders | ||||||||||
| Chills | 0/3 (0%) | 0/6 (0%) | 8/30 (26.7%) | 5/32 (15.6%) | 3/24 (12.5%) | |||||
| Edema face | 0/3 (0%) | 0/6 (0%) | 4/30 (13.3%) | 4/32 (12.5%) | 3/24 (12.5%) | |||||
| Edema limbs | 0/3 (0%) | 0/6 (0%) | 6/30 (20%) | 2/32 (6.3%) | 2/24 (8.3%) | |||||
| Facial pain | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 2/24 (8.3%) | |||||
| Fall | 0/3 (0%) | 1/6 (16.7%) | 4/30 (13.3%) | 3/32 (9.4%) | 2/24 (8.3%) | |||||
| Fatigue | 2/3 (66.7%) | 3/6 (50%) | 26/30 (86.7%) | 18/32 (56.3%) | 17/24 (70.8%) | |||||
| Fever | 0/3 (0%) | 0/6 (0%) | 6/30 (20%) | 3/32 (9.4%) | 1/24 (4.2%) | |||||
| Flu like symptoms | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Hypothermia | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Infusion related reaction | 0/3 (0%) | 1/6 (16.7%) | 3/30 (10%) | 0/32 (0%) | 2/24 (8.3%) | |||||
| Irritability | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Localized edema | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Localized edema | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Malaise | 0/3 (0%) | 0/6 (0%) | 6/30 (20%) | 3/32 (9.4%) | 1/24 (4.2%) | |||||
| Neck edema | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Non-cardiac chest pain | 0/3 (0%) | 1/6 (16.7%) | 5/30 (16.7%) | 0/32 (0%) | 3/24 (12.5%) | |||||
| Pain | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 1/32 (3.1%) | 1/24 (4.2%) | |||||
| Pain in extremity | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Restless leg | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Upper back edema | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Hepatobiliary disorders | ||||||||||
| Cholecystitis | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Immune system disorders | ||||||||||
| Allergic reaction | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Infections and infestations | ||||||||||
| Bone infection | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Bronchial infection | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Eye infection | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Folliculitis | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Gastrointestinal infection | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Herpertic blepharitis | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Lung infection | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Nail infection | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Otitis media | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Paronychia | 0/3 (0%) | 1/6 (16.7%) | 12/30 (40%) | 5/32 (15.6%) | 5/24 (20.8%) | |||||
| Sepsis | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Sinusitis | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Skin infection | 1/3 (33.3%) | 0/6 (0%) | 6/30 (20%) | 3/32 (9.4%) | 1/24 (4.2%) | |||||
| Upper respiratory infection | 1/3 (33.3%) | 0/6 (0%) | 2/30 (6.7%) | 2/32 (6.3%) | 1/24 (4.2%) | |||||
| Urinary tract infection | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Wound infection | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Bruising | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Hand wound | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Inguinal hernia | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Intestinal stoma leak | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Skin ulceration | 0/3 (0%) | 0/6 (0%) | 4/30 (13.3%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Tracheal hemorrhage | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Investigations | ||||||||||
| Activated partial thromboplastin time prolonged | 1/3 (33.3%) | 1/6 (16.7%) | 5/30 (16.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Alanine aminotransferase increased | 0/3 (0%) | 2/6 (33.3%) | 7/30 (23.3%) | 1/32 (3.1%) | 2/24 (8.3%) | |||||
| Alkaline phosphatase increased | 0/3 (0%) | 1/6 (16.7%) | 7/30 (23.3%) | 6/32 (18.8%) | 7/24 (29.2%) | |||||
| Aspartate aminotransferase increased | 0/3 (0%) | 1/6 (16.7%) | 10/30 (33.3%) | 6/32 (18.8%) | 6/24 (25%) | |||||
| Blood bilirubin increased | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| CPK increased | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Cardiac troponin I increased | 0/3 (0%) | 0/6 (0%) | 3/30 (10%) | 0/32 (0%) | 0/24 (0%) | |||||
| Cholesterol high | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 1/24 (4.2%) | |||||
| Creatinine increased | 1/3 (33.3%) | 2/6 (33.3%) | 8/30 (26.7%) | 2/32 (6.3%) | 5/24 (20.8%) | |||||
| Electrocardiogram QT corrected interval prolonged | 0/3 (0%) | 0/6 (0%) | 10/30 (33.3%) | 2/32 (6.3%) | 1/24 (4.2%) | |||||
| GGT increased | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| INR increased | 1/3 (33.3%) | 2/6 (33.3%) | 15/30 (50%) | 7/32 (21.9%) | 4/24 (16.7%) | |||||
| Lipase increased | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Lymphocyte count decreased | 3/3 (100%) | 6/6 (100%) | 28/30 (93.3%) | 14/32 (43.8%) | 19/24 (79.2%) | |||||
| Neutrophil count decreased | 2/3 (66.7%) | 4/6 (66.7%) | 26/30 (86.7%) | 18/32 (56.3%) | 14/24 (58.3%) | |||||
| Platelet count decreased | 2/3 (66.7%) | 3/6 (50%) | 23/30 (76.7%) | 23/32 (71.9%) | 16/24 (66.7%) | |||||
| Weight loss | 0/3 (0%) | 0/6 (0%) | 15/30 (50%) | 9/32 (28.1%) | 8/24 (33.3%) | |||||
| White blood cell decreased | 2/3 (66.7%) | 6/6 (100%) | 26/30 (86.7%) | 23/32 (71.9%) | 19/24 (79.2%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Acidosis | 0/3 (0%) | 0/6 (0%) | 4/30 (13.3%) | 3/32 (9.4%) | 0/24 (0%) | |||||
| Anorexia | 1/3 (33.3%) | 2/6 (33.3%) | 17/30 (56.7%) | 6/32 (18.8%) | 7/24 (29.2%) | |||||
| Dehydration | 1/3 (33.3%) | 1/6 (16.7%) | 5/30 (16.7%) | 5/32 (15.6%) | 1/24 (4.2%) | |||||
| Glucose intolerance | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 2/32 (6.3%) | 0/24 (0%) | |||||
| Hypercalcemia | 1/3 (33.3%) | 0/6 (0%) | 8/30 (26.7%) | 4/32 (12.5%) | 1/24 (4.2%) | |||||
| Hyperglycemia | 1/3 (33.3%) | 1/6 (16.7%) | 10/30 (33.3%) | 11/32 (34.4%) | 1/24 (4.2%) | |||||
| Hyperkalemia | 1/3 (33.3%) | 0/6 (0%) | 4/30 (13.3%) | 3/32 (9.4%) | 1/24 (4.2%) | |||||
| Hyperlipidemia | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 3/24 (12.5%) | |||||
| Hypermagnesemia | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Hypernatremia | 0/3 (0%) | 0/6 (0%) | 6/30 (20%) | 5/32 (15.6%) | 0/24 (0%) | |||||
| Hypertriglyceridemia | 0/3 (0%) | 1/6 (16.7%) | 1/30 (3.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Hypoalbuminemia | 3/3 (100%) | 3/6 (50%) | 20/30 (66.7%) | 15/32 (46.9%) | 7/24 (29.2%) | |||||
| Hypocalcemia | 2/3 (66.7%) | 4/6 (66.7%) | 17/30 (56.7%) | 7/32 (21.9%) | 5/24 (20.8%) | |||||
| Hypoglycemia | 1/3 (33.3%) | 0/6 (0%) | 5/30 (16.7%) | 3/32 (9.4%) | 1/24 (4.2%) | |||||
| Hypokalemia | 0/3 (0%) | 1/6 (16.7%) | 13/30 (43.3%) | 9/32 (28.1%) | 2/24 (8.3%) | |||||
| Hypomagnesemia | 2/3 (66.7%) | 2/6 (33.3%) | 13/30 (43.3%) | 10/32 (31.3%) | 5/24 (20.8%) | |||||
| Hyponatremia | 1/3 (33.3%) | 4/6 (66.7%) | 22/30 (73.3%) | 13/32 (40.6%) | 5/24 (20.8%) | |||||
| Hypophosphatemia | 1/3 (33.3%) | 2/6 (33.3%) | 7/30 (23.3%) | 4/32 (12.5%) | 2/24 (8.3%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 2/24 (8.3%) | |||||
| Axilla pain | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Back pain | 0/3 (0%) | 2/6 (33.3%) | 9/30 (30%) | 2/32 (6.3%) | 4/24 (16.7%) | |||||
| Clavicular pain | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Flank pain | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Generalized muscle weakness | 0/3 (0%) | 0/6 (0%) | 6/30 (20%) | 2/32 (6.3%) | 0/24 (0%) | |||||
| Head soft tissue necrosis | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Hip pain | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Jaw pain | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Joint range of motion decreased cervical spine | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 2/32 (6.3%) | 0/24 (0%) | |||||
| Knee pain | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Kyphosis | 0/3 (0%) | 0/6 (0%) | 4/30 (13.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Muscle weakness left sided | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Myalgia | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 1/24 (4.2%) | |||||
| Myositis | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Neck pain | 0/3 (0%) | 0/6 (0%) | 9/30 (30%) | 6/32 (18.8%) | 3/24 (12.5%) | |||||
| Osteonecrosis of jaw | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Osteonecrosis of lunate | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Shoulder pain | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Superficial soft tissue fibrosis | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 2/32 (6.3%) | 1/24 (4.2%) | |||||
| Trismus | 1/3 (33.3%) | 0/6 (0%) | 6/30 (20%) | 8/32 (25%) | 4/24 (16.7%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Tumor hemorrhage | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Tumor pain | 0/3 (0%) | 1/6 (16.7%) | 8/30 (26.7%) | 7/32 (21.9%) | 3/24 (12.5%) | |||||
| Nervous system disorders | ||||||||||
| Abdominal numbness | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Dizziness | 0/3 (0%) | 0/6 (0%) | 6/30 (20%) | 9/32 (28.1%) | 3/24 (12.5%) | |||||
| Dysarthria | 1/3 (33.3%) | 0/6 (0%) | 9/30 (30%) | 7/32 (21.9%) | 4/24 (16.7%) | |||||
| Dysgeusia | 0/3 (0%) | 0/6 (0%) | 3/30 (10%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Encephalopathy | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Facial drooping | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 3/32 (9.4%) | 0/24 (0%) | |||||
| Facial palsy | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Headache | 0/3 (0%) | 0/6 (0%) | 9/30 (30%) | 6/32 (18.8%) | 3/24 (12.5%) | |||||
| Hypersomnia | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Lethargy | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Memory impairment | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Movements involuntary | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Neuralgia | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Peripheral sensory neuropathy | 0/3 (0%) | 3/6 (50%) | 7/30 (23.3%) | 5/32 (15.6%) | 1/24 (4.2%) | |||||
| Presyncope | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Syncope | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 3/32 (9.4%) | 0/24 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Agitation | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Anxiety | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 3/32 (9.4%) | 2/24 (8.3%) | |||||
| Confusion | 0/3 (0%) | 0/6 (0%) | 7/30 (23.3%) | 1/32 (3.1%) | 1/24 (4.2%) | |||||
| Depression | 0/3 (0%) | 1/6 (16.7%) | 3/30 (10%) | 4/32 (12.5%) | 1/24 (4.2%) | |||||
| Hallucinations | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 2/24 (8.3%) | |||||
| Insomnia | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 3/24 (12.5%) | |||||
| Renal and urinary disorders | ||||||||||
| Acute kidney injury | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Hematuria | 1/3 (33.3%) | 0/6 (0%) | 9/30 (30%) | 4/32 (12.5%) | 2/24 (8.3%) | |||||
| Proteinuria | 0/3 (0%) | 0/6 (0%) | 7/30 (23.3%) | 2/32 (6.3%) | 1/24 (4.2%) | |||||
| Urinary frequency | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Urinary retention | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 2/32 (6.3%) | 1/24 (4.2%) | |||||
| Urine discoloration | 0/3 (0%) | 0/6 (0%) | 3/30 (10%) | 0/32 (0%) | 0/24 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Pelvic pain | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Vaginal hemorrhage | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Adult respiratory distress syndrome | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Allergic Rhinitis | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Aspiration | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 4/32 (12.5%) | 0/24 (0%) | |||||
| Atelectasis | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 2/24 (8.3%) | |||||
| Bronchial obstruction | 0/3 (0%) | 1/6 (16.7%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Chronic obstructive pulmonary disease | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Cough | 1/3 (33.3%) | 2/6 (33.3%) | 10/30 (33.3%) | 11/32 (34.4%) | 6/24 (25%) | |||||
| Dyspnea | 0/3 (0%) | 2/6 (33.3%) | 19/30 (63.3%) | 10/32 (31.3%) | 8/24 (33.3%) | |||||
| Epistaxis | 0/3 (0%) | 0/6 (0%) | 5/30 (16.7%) | 5/32 (15.6%) | 3/24 (12.5%) | |||||
| Hemoptysis | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Hiccups | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Hoarseness | 1/3 (33.3%) | 0/6 (0%) | 7/30 (23.3%) | 4/32 (12.5%) | 2/24 (8.3%) | |||||
| Hypoxia | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 2/32 (6.3%) | 0/24 (0%) | |||||
| Laryngeal hemorrhage | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Laryngeal inflammation | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Laryngeal obstruction | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Left vocal cord paralysis | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Nasal congestion | 0/3 (0%) | 1/6 (16.7%) | 6/30 (20%) | 3/32 (9.4%) | 3/24 (12.5%) | |||||
| Nasal regurgitation of liquids | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Oromaxillary fistula | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Pharyngeal fistula | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Pharyngeal hemorrhage | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Pleural effusion | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 4/32 (12.5%) | 1/24 (4.2%) | |||||
| Pneumothorax | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Postnasal drip | 1/3 (33.3%) | 2/6 (33.3%) | 2/30 (6.7%) | 3/32 (9.4%) | 1/24 (4.2%) | |||||
| Productive cough | 0/3 (0%) | 0/6 (0%) | 13/30 (43.3%) | 6/32 (18.8%) | 5/24 (20.8%) | |||||
| Respiratory failure | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Sleep apnea | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 2/24 (8.3%) | |||||
| Sore throat | 0/3 (0%) | 0/6 (0%) | 7/30 (23.3%) | 3/32 (9.4%) | 2/24 (8.3%) | |||||
| Voice alteration | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Wheezing | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Alopecia | 0/3 (0%) | 0/6 (0%) | 8/30 (26.7%) | 5/32 (15.6%) | 2/24 (8.3%) | |||||
| Bed sores | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Blisters on palms and toe | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Dermal neck nodules | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Dry skin | 2/3 (66.7%) | 2/6 (33.3%) | 18/30 (60%) | 11/32 (34.4%) | 10/24 (41.7%) | |||||
| Erythema multiforme | 0/3 (0%) | 0/6 (0%) | 7/30 (23.3%) | 3/32 (9.4%) | 0/24 (0%) | |||||
| Increased mucous secretions | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Lesion (unknown/furuncle) | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Nail loss | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Nail ridging | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Night sweats | 0/3 (0%) | 0/6 (0%) | 2/30 (6.7%) | 0/32 (0%) | 0/24 (0%) | |||||
| Palmar-plantar erythrodysesthesia syndrome | 1/3 (33.3%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Periorbital edema | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Photosensitivity | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 0/32 (0%) | 0/24 (0%) | |||||
| Pruritus | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 2/32 (6.3%) | 0/24 (0%) | |||||
| Rash acneiform | 2/3 (66.7%) | 5/6 (83.3%) | 21/30 (70%) | 15/32 (46.9%) | 20/24 (83.3%) | |||||
| Rash maculo-papular | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 3/32 (9.4%) | 1/24 (4.2%) | |||||
| Skin hyperpigmentation | 0/3 (0%) | 0/6 (0%) | 4/30 (13.3%) | 3/32 (9.4%) | 0/24 (0%) | |||||
| Skin induration | 0/3 (0%) | 0/6 (0%) | 10/30 (33.3%) | 6/32 (18.8%) | 2/24 (8.3%) | |||||
| Skin ulceration | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Telangiectasia | 1/3 (33.3%) | 0/6 (0%) | 0/30 (0%) | 0/32 (0%) | 0/24 (0%) | |||||
| Vascular disorders | ||||||||||
| Hematoma | 0/3 (0%) | 0/6 (0%) | 1/30 (3.3%) | 1/32 (3.1%) | 0/24 (0%) | |||||
| Hypertension | 2/3 (66.7%) | 4/6 (66.7%) | 25/30 (83.3%) | 13/32 (40.6%) | 12/24 (50%) | |||||
| Hypotension | 0/3 (0%) | 0/6 (0%) | 7/30 (23.3%) | 5/32 (15.6%) | 2/24 (8.3%) | |||||
| Lymphedema | 0/3 (0%) | 0/6 (0%) | 4/30 (13.3%) | 0/32 (0%) | 1/24 (4.2%) | |||||
| Thromboembolic event | 0/3 (0%) | 0/6 (0%) | 0/30 (0%) | 1/32 (3.1%) | 0/24 (0%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE 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 | Douglas R. Adkins, M.D. |
|---|---|
| Organization | Washington University School of Medicine |
| Phone | 314-362-4471 |
| dadkins@wustl.edu |
Responsible Party:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT02101034
Other Study ID Numbers:
- 201404139
First Posted:
Apr 1, 2014
Last Update Posted:
May 25, 2022
Last Verified:
May 1, 2022