PD 0332991 and Cetuximab in Patients With Incurable SCCHN | NCT02101034

NCT02101034

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Name	Class
Pfizer	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase I: Dose Level 1	Experimental	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 Drug: PD 0332991
Phase I: Dose Level 2	Experimental	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 Drug: PD 0332991
Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Experimental	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 Drug: PD 0332991
Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Experimental	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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Cetuximab	Biological		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:

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase I - Maximum Tolerated Dose (MTD)	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	6 months (estimated completion of Phase I)
Phase II: Efficacy as Measured by Overall Response Rate	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	End of treatment (estimated to be 12 months)

Secondary Outcomes

Measure	Description	Time Frame
Phase I: Most Frequent Adverse Events	Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	Up to 30 days following completion of treatment (estimated to be 13 months)
Phase II: PD 0332991 Related Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events

Eligibility Module

Eligibility Criteria

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/Locations Module

Name	Affiliation	Role
Douglas Adkins, M.D.	Washington University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Winship Cancer Institute of Emory University		Atlanta	Georgia	30322	United States
University of Kansas

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
31351869	Derived	Adkins D, Ley J, Neupane P, Worden F, Sacco AG, Palka K, Grilley-Olson JE, Maggiore R, Salama NN, Trinkaus K, Van Tine BA, Steuer CE, Saba NF, Oppelt P. Palbociclib and cetuximab in platinum-resistant and in cetuximab-resistant human papillomavirus-unrelated head and neck cancer: a multicentre, multigroup, phase 2 trial. Lancet Oncol. 2019 Sep;20(9):1295-1305. doi: 10.1016/S1470-2045(19)30405-X. Epub 2019 Jul 24.

Label	URL
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine	View source

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	Phase I: Dose Level 1	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.
FG001	Phase I: Dose Level 2	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.
FG002	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	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.
FG003	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	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.
FG004	Phase II Arm 3:	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.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0003 subjects FG0016 subjects FG00231 subjects FG00332 subjects FG00424 subjects
COMPLETED		FG0003 subjects FG0016 subjects FG00230 subjects FG00332 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0021 subjects FG0030 subjects FG004

Type	Comment	Reasons
Enrolled but did not start treatment		FG0000 subjects FG0010 subjects FG0021 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Phase I: Dose Level 1	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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase I - Maximum Tolerated Dose (MTD)

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

Only Phase I participants were evaluable for this outcome measure.

Posted

Number

6 months (estimated completion of Phase I)

ID	Title

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase I: Dose Level 1	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.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Douglas R. Adkins, M.D.	Washington University School of Medicine	314-362-4471		dadkins@wustl.edu

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Oct 24, 2017	Feb 24, 2021	Prot_SAP_000.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D000077195	Squamous Cell Carcinoma of Head and Neck

ID	Term
D002294	Carcinoma, Squamous Cell
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type

Intervention Browse Module

ID	Term
D000068818	Cetuximab
C500026	palbociclib

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins

Masking Info

EG0000 affected3 at risk

EG0010 affected6 at risk

EG0021 affected30 at risk

EG0030 affected32 at risk

EG0040 affected24 at risk

EG0003 affected3 at risk

EG0016 affected6 at risk

EG00230 affected30 at risk

EG00324 affected32 at risk

EG00417 affected24 at risk

Title	Measurements
	OG00028

Title	Measurements
	OG00023

Title	Measurements
	OG00037

OG000	Phase I: Dose Level 1 and Dose Level 2	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.
OG001	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	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.
OG002	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	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.
OG003	Phase II Arm 3:	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.