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PD 0332991 and Cetuximab in Patients With Incurable SCCHN

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ClinicalTrials.gov Identifier: NCT02101034
Recruitment Status : Recruiting
First Posted : April 1, 2014
Last Update Posted : September 25, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Washington University School of Medicine

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
Carcinoma, Squamous Cell of Head and Neck Biological: Cetuximab Drug: PD 0332991 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 93 participants
Allocation: Non-Randomized
Intervention Model: Single Group 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
Study Start Date : June 17, 2014
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine


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 Name: Erbitux®

Drug: PD 0332991
Other Name: palbociclib

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 Name: Erbitux®

Drug: PD 0332991
Other Name: palbociclib

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 Name: Erbitux®

Drug: PD 0332991
Other Name: palbociclib

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 Name: Erbitux®

Drug: PD 0332991
Other Name: palbociclib

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 Name: Erbitux®

Drug: PD 0332991
Other Name: palbociclib




Primary Outcome Measures :
  1. 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


  2. 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


  3. 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


  4. 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



Secondary Outcome Measures :
  1. 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

  2. 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.


  3. 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.


  4. 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.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02101034


Contacts
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Contact: Douglas Adkins, M.D. 314-362-4471 dadkins@wustl.edu

Locations
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United States, Arkansas
University of Arkansas Withdrawn
Fayetteville, Arkansas, United States, 72701
United States, California
University of California - San Diego Withdrawn
San Diego, California, United States, 92093
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Conor Steuer, M.D.    404-778-1900    csteuer@emory.edu   
Principal Investigator: Conor Steuer, M.D.         
Sub-Investigator: Nabil Saba, M.D.         
United States, Kansas
University of Kansas Active, not recruiting
Westwood, Kansas, United States, 66205
United States, Michigan
University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Francis P Worden, M.D.    734-647-8906    fworden@med.umich.edu   
Principal Investigator: Francis P Worden, M.D.         
Sub-Investigator: Thomas Carey, Ph.D.         
Sub-Investigator: Alexander Pearson, M.D.         
Sub-Investigator: Susan G Urba, M.D.         
United States, Minnesota
Mayo Clinic Withdrawn
Rochester, Minnesota, United States, 55905
United States, Missouri
Saint Louis University Cancer Center Withdrawn
Saint Louis, Missouri, United States, 63110
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Douglas Adkins, M.D.    314-362-4471    dadkins@wustl.edu   
Principal Investigator: Douglas Adkins, M.D.         
Sub-Investigator: Tanya Wildes, M.D.         
United States, New York
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Ronald Maggiore, M.D.    585-275-0394    ronald.maggiore@urmc.rochester.edu   
Principal Investigator: Ronald Maggiore, M.D.         
Sub-Investigator: Megan Baumgart, M.D.         
Sub-Investigator: Deborah Mulford, M.D.         
United States, North Carolina
University of North Carolina Withdrawn
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
Washington University School of Medicine
Pfizer
Investigators
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Principal Investigator: Douglas Adkins, M.D. Washington University School of Medicine

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02101034     History of Changes
Other Study ID Numbers: 201404139
First Posted: April 1, 2014    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Cetuximab
Palbociclib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action