Reirradiation With Pembrolizumab in Locoregional Inoperable Recurrence or Second Primary Squamous Cell CA of the Head and Neck

NCT02289209 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCC 18-009
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

Eligible participants with locoregional inoperable recurrence or second primary squamous cell carcinoma of the head and neck will be treated with reirradiation combined with anti-PD-1 mAb MK-3475 (generic name: pembrolizumab, trade name Keytruda®).

Conditions

Recurrent Head and Neck Cancer; Carcinoma, Squamous Cell of Head and Neck

Keywords

head and neck cancer; reirradiation; MK-3475; Anti-PD-1 monoclonal antibody; Squamous cell carcinoma; Keytruda; pembrolizumab

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Number of months from the date of initiation of treatment to the date of progression of disease or death (whichever occurs first). Progressive disease, per RECIST 1.1, is defined as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

  Up to 36 months (after starting reirradiation and MK-3475)

Secondary Outcomes (14)

• Best Overall Response Rate (ORR)

  Up to 36 months (after initiation of treatment with reirradiation and MK-3475)

• Clinical Benefit Rate (CBR)

  Up to 36 months (after initiation of treatment with reirradiation and MK-3475)

• Time to in Field Disease Progression

  Up to 36 months (after initiation of treatment with reirradiation and MK-3475)

• Overall Survival (OS)

  Up to 36 months (after initiation of treatment with reirradiation and MK-3475)

• Quality of Life Using EORTC QLQ-C30 - Baseline

  At Baseline

Study Arms (1)

Reirradiation + MK-3475

EXPERIMENTAL

Reirradiation 1.2 Gy BID for 5 days a week for 5 weeks with MK-3475 (Keytruda, pembrolizumab) 200mg intravenous every 3 weeks until 3 months post completion of reirradiation.

Radiation: Reirradiation; Drug: MK-3475

Interventions

Reirradiation RADIATION

Reirradiation 1.2 GY BID 5 days a week for 5 weeks.

Reirradiation + MK-3475

MK-3475 DRUG

MK-3475 will be given at 200mg intravenous every 3 weeks starting day one of reirradiation and will be continued once every 3 weeks until 3 months post completion of reirradiation. Further continuation of MK-3475 will be determined by response evaluation at 3 months post completion of reirradiation

Also known as: Keytruda, pembrolizumab

Reirradiation + MK-3475

Eligibility Criteria

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

You may qualify if:

• Have received only prior radiation treatment course. Prior radiation course must have been with curative intent.
• At least 6 months since completion of radiation
• Based on prior radiation records, have had most of the tumor volume (\>50%) previously radiated at doses \> 45 Gy without exceeding spinal cord tolerance (combining previous and future radiation dose to spinal cord of \< 50 Gy).
• Be willing to undergo percutaneous endoscopic gastrostomy (PEG) placement, if necessary.
• Have at least one measurable area of disease based on RECIST 1.1 within the previously radiated field.
• Have provided adequate tissue for PD-L1 analysis either from an archival tissue sample or fresh biopsy done to confirm recurrence/second primary. Archival tissue sample can only be used if done within 3 months of enrollment on the clinical trial.
• Performance status of 0 or 1 on the ECOG Performance Scale.
• Life expectancy greater than 12 weeks
• Adequate organ function as defined by the protocol

You may not qualify if:

• Presence of distant metastatic disease.
• Is currently participating in or has participated in a study of an investigational agent or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has had a prior monoclonal antibody, chemotherapy, or targeted small molecule therapy within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier.
• History of other malignancy within 5 years with the exception of prior Squamous cell carcinoma of the head and neck, adequately treated basal cell or squamous cell skin cancer, or carcinoma of the cervix.
• Has an active autoimmune disease
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Has received a live vaccine within 30 days prior to the first dose of trial treatment
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.

Sponsors & Collaborators

• Dan Zandberg: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

Univeristy of Maryland - Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell

Interventions

Re-Irradiation; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Retreatment

Results Point of Contact

• Title: Barbara Stadterman, MPH, CCRP
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

4126475554

Study Officials

• Dan Zandberg, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: November 13, 2014
• Study Start: March 9, 2016
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2024
• Last Updated: March 6, 2025
• Results First Posted: March 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)