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Trial record 1 of 1 for:    NCT02101034
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PD 0332991 and Cetuximab in Patients With Incurable SCCHN

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ClinicalTrials.gov Identifier: NCT02101034
Recruitment Status : Active, not recruiting
First Posted : April 1, 2014
Last Update Posted : October 30, 2020
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE March 27, 2014
First Posted Date  ICMJE April 1, 2014
Last Update Posted Date October 30, 2020
Actual Study Start Date  ICMJE June 17, 2014
Actual Primary Completion Date June 8, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2017)
  • Phase I - Maximum tolerated dose (MTD) [ Time Frame: 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 (platin-resistant group) [ Time Frame: 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
  • Phase II: Efficacy as measured by overall response rate (cetuximab-resistant HPV-unrelated SCCHN) [ Time Frame: 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
  • Phase II: Efficacy as measured by overall response rate (cetuximab-resistant HPV-related SCCHN) [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2014)
  • Phase I-MTD [ Time Frame: 26 months ]
    MTD is the dose level immediately below the dose level at which 2 patients of a cohort experience DLT during the first cycle Dose Limiting Toxicities (DLTs) Hematologic DLT is defined as any of the following that occur during the first cycle that are attributed as possibly, probably, or definitely related to the treatment grade 4 neutropenia ≥7 day duration grade 4 infection with grade 3 or 4 neutropenia grade 4 thrombocytopenia associated with life-threatening bleeding treatment held for >14 days due to hematologic toxicity febrile neutropenia of any duration with temperature >38.5°C Non-hematologic DLT is defined as any possibly, probably, or definitely related grade 3 or 4 non-hematologic toxicity that occurs during the first cycle with the following specific exceptions suboptimally treated grade 3 or 4 nausea, vomiting, diarrhea, anorexia, or lymphopenia grade 3 metabolic abnormalities any hypersensitivity / infusion reaction or acneiform rash due to cetuximab
  • Phase II Efficacy of PD 0332991 and cetuximab [ Time Frame: 92 months ]
    Measured by overall response rate (ORR=CR+PR) defined by RECIST criteria and by time to progression (TTP). 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2014)
  • Phase I & Phase II: Adverse events [ Time Frame: Up to 30 days following completion of treatment ]
    Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
  • Phase II: Progression free survival (PFS) [ Time Frame: 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) [ Time Frame: 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/stable disease [ Time Frame: Up to 5 years ]
    Participants will be followed every 2 months for 5 years or until death, whichever occurs first. 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. Duration of disease control (CR, PR, stable disease) is measured from the start of treatment until the criteria for progression are met.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2014)
  • Adverse events [ Time Frame: 26 months ]
    Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
  • Progression free survival (PFS) [ Time Frame: 92 months ]
    Duration of time from start of treatment to time of progression or death, whichever occurs first.
  • Overall survival (OS) [ Time Frame: 92 months ]
    Time measurement criteria are first met for CR until the first date that progressive disease is objectively documented.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PD 0332991 and Cetuximab in Patients With Incurable SCCHN
Official Title  ICMJE Phase I/II Trial of the Addition of PD 0332991 to Cetuximab in Patients With Incurable SCCHN
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Squamous Cell of Head and Neck
Intervention  ICMJE
  • Biological: Cetuximab
    Other Name: Erbitux®
  • Drug: PD 0332991
    Other Name: palbociclib
Study Arms  ICMJE
  • 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.

    Interventions:
    • Biological: Cetuximab
    • Drug: PD 0332991
  • 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.

    Interventions:
    • Biological: Cetuximab
    • Drug: PD 0332991
  • 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.

    Interventions:
    • Biological: Cetuximab
    • Drug: PD 0332991
  • 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.

    Interventions:
    • Biological: Cetuximab
    • Drug: PD 0332991
  • 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.

    Interventions:
    • Biological: Cetuximab
    • Drug: PD 0332991
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 29, 2020)
96
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2014)
42
Estimated Study Completion Date  ICMJE October 31, 2024
Actual Primary Completion Date June 8, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02101034
Other Study ID Numbers  ICMJE 201404139
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Douglas Adkins, M.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP