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Carcinoma, Squamous Cell of Head and NeckPhase 1/2NCT02101034

PD 0332991 and Cetuximab in Patients With Incurable SCCHN

A Phase 1/2 study testing Cetuximab and PD 0332991 in people with Carcinoma, Squamous Cell of Head and Neck, run by Washington University School of Medicine at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cetuximab and PD 0332991
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
5 sitesUnited States
Study dates
17 Jun 2014to 10 Nov 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Michigan Health System

    Ann Arbor, Michigan, 48109

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • University of Kansas

    Westwood, Kansas, 66205

Other trials in United States

About this study

Official title: Phase I/II Trial of the Addition of PD 0332991 to Cetuximab in Patients With Incurable SCCHN

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.

Being tested
Cetuximab, PD 0332991
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CetuximabBiological

    Also called Erbitux®

  • PD 0332991Drug

    Also called palbociclib

Study groups in NCT02101034
Study groupRoleWhat they receive
Phase I: Dose Level 1ExperimentalPD 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.
Receives: Biological: Cetuximab; Drug: PD 0332991
Phase I: Dose Level 2ExperimentalPD 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.
Receives: Biological: Cetuximab; Drug: PD 0332991
Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHNExperimentalPD 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.
Receives: Biological: Cetuximab; Drug: PD 0332991
Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHNExperimentalPD 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.
Receives: Biological: Cetuximab; Drug: PD 0332991
Phase II Arm 3:ExperimentalPD 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.
Receives: Biological: Cetuximab; Drug: PD 0332991

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 6 months (estimated completion of Phase I)

  2. 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

    Measured: End of treatment (estimated to be 12 months)

Secondary outcomes (7)

  1. Phase I: Most Frequent Adverse Events

    Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: Up to 30 days following completion of treatment (estimated to be 13 months)

  2. Phase II: PD 0332991 Related Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events

    Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: Up to 30 days following completion of treatment (estimated to be 13 months)

  3. Phase II: Cetuximab Related Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events

    Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: Up to 30 days following completion of treatment (estimated to be 13 months)

  4. Phase II: Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events

    Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: Up to 30 days following completion of treatment (estimated to be 13 months)

  5. Phase II: Progression Free Survival (PFS)

    Participants were followed every 2 months for up to 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.

    Measured: Up to 5 years

  6. Phase II: Overall Survival (OS)

    Participants were followed every 2 months for up to 5 years or until death, whichever occurs first.

    Overall survival is measured from time of diagnosis to time of death.

    Measured: Up to 5 years

  7. Phase II: Duration of Response

    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.

    Measured: Completion of treatment (estimated to be 12 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2014 (estimated)
  2. Study start17 Jun 2014
  3. Primary completion8 Jun 2020
  4. Study completion10 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02101034
Sponsor's protocol ID
201404139
Status last verified
Dec 2023
First submitted
27 Mar 2014
Last updated
21 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 31351869

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cetuximab and PD 0332991 in people with Carcinoma, Squamous Cell of Head and Neck, run by Washington University School of Medicine at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I - Maximum Tolerated Dose (MTD) (time frame: 6 months (estimated completion of Phase I)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02101034, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2023.

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