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Palbociclib With Cetuximab and IMRT for Locally Advanced Squamous Cell Carcinoma

NCT03024489 · Status: ACTIVE_NOT_RECRUITING · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 27

Last updated 2024-03-15

No results posted yet for this study

Summary

Cyclin D kinase 4 (CDK4) is a key regulator of the G1-S transition in the cell cycle. Alterations in CDK4-cyclin D-retinoblastoma (Rb) pathway may lead to carcinogenesis in many cancers. Several mechanisms have been described: (i) Amplification or overexpression of cyclin D1, (ii) Amplification of CDK4, (iii) Activating mutation of CDK4, and (iv) Loss of the CDK4 inhibitor, p16 (CDKN2A). Human Papilloma Virus (HPV) plays a major role in squamous cell carcinoma of head and neck (SCCHN) carcinogenesis. It induces many alterations in the CDK4-Cyclin D-Rb and apoptotic pathways such as up-regulation of p16, loss of Rb and p53 functions. A novel therapy for HPV-negative SCCHN is clearly an unmet medical need.

Palbociclib (PD 0332991) is an orally active, highly selective inhibitor of the CDK4/6 with ability to block Rb phosphorylation in the low nanomolar range. The most advanced development is in a treatment of metastatic breast cancer. In addition, palbociclib showed a radiosensitization property. Since combination of cetuximab and radiation improved PFS and overall survival (OS) in locally advanced SCCHN when compared with radiation alone, these provide a strong rationale to evaluate a combination of palbociclib, cetuximab, and radiation for locally advanced SCCHN. Because many genetic alterations in SCCHN significantly involve in the CDK4-cyclin D-Rb pathway, predictive biomarker(s) of palbociclib in this combination will be explored.

Thus, the investigators propose a non-randomized, dose escalation, phase I study designed to determine the maximum tolerated dose (MTD) and toxicity of palbociclib, cetuximab, and IMRT for locally advanced SCCHN.

Conditions

Interventions

DRUG

Palbociclib

Dose Level -1: 100 mg oral every other day 3 week-on and 1-week of during IMRT (Day 1-21 and Day 29-49).

DRUG

Palbociclib

Dose Level 1: 75 mg per oral daily 3 week-on and 1-week of during IMRT (Day 1-21 and Day 29-49).

DRUG

Palbociclib

Dose Level 2: 100 mg per oral daily 3 week-on and 1-week of during IMRT (Day 1-21 and Day 29-49).

DRUG

Palbociclib

Dose Level 3: 125 mg per oral daily 3 week-on and 1-week of during IMRT (Day 1-21 and Day 29-49).

DRUG

Cetuximab

All dose levels: 400 mg/m2 IV at 7 days before (day -7) starting radiation and then 250 mg/m2 IV weekly for 7 weeks.

RADIATION

Intensity Modulated Radiation Therapy

5 days on/2 days off with a total dose of 70 Gy for 33-35 fractions.

Sponsors & Collaborators

  • Mahidol University

    lead OTHER

Principal Investigators

  • Nuttapong Ngamphaiboon, MD · Ramathibodi Hospital

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2017-07-19
Primary Completion
2024-03-11
Completion
2024-12-31
FDA Drug
Yes

Countries

  • Thailand

Study Locations

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03024489 on ClinicalTrials.gov