PD 0332991 and Cetuximab in Patients With Incurable SCCHN

NCT02101034 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 201404139
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 5

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.

Conditions

Carcinoma, Squamous Cell of Head and Neck

Outcome Measures

Primary Outcomes (2)

• 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 (7)

• Phase I: Most Frequent Adverse Events

  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

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

• 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)

• 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)

• Phase II: Progression Free Survival (PFS)

  Up to 5 years

Study Arms (5)

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.

Biological: Cetuximab; Drug: PD 0332991

Phase II Arm 3:

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

Interventions

Cetuximab BIOLOGICAL

Also known as: Erbitux®

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:

PD 0332991 DRUG

Also known as: palbociclib

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:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Pfizer: collaborator

Study Sites (5)

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

University of Kansas

Westwood, Kansas, 66205, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Related Publications (1)

• 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.

  PMID: 31351869 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab; palbociclib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Douglas R. Adkins, M.D.
• Organization: Washington University School of Medicine

dadkins@wustl.edu

314-362-4471

Study Officials

• Douglas Adkins, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2014
• First Posted: April 1, 2014
• Study Start: June 17, 2014
• Primary Completion: June 8, 2020
• Study Completion: November 10, 2023
• Last Updated: December 21, 2023
• Results First Posted: June 11, 2021

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)