Photodynamic Therapy With HPPH Compared to Standard of Care Surgery in Treating Patients With Oral Cavity Cancer

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03090412
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 2
• Locations: 2
• Arms: 2
• Actual Duration (Months): 41
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase II clinical trial studies how well photodynamic therapy with HPPH works compared to standard of care surgery in treating patients with oral cavity cancer. Photodynamic therapy can destroy or control disease by using a combination of drug, such as HPPH, and light and may be as effective as surgery in treating patients with oral cavity cancer.

Condition or Disease	Intervention/Treatment	Phase
Stage I Oral Cavity Squamous Cell Carcinoma; Stage II Oral Cavity Squamous Cell Carcinoma	Drug: HPPH; Other: Laboratory Biomarker Analysis; Drug: Photodynamic Therapy; Other: Quality-of-Life Assessment; Procedure: Therapeutic Conventional Surgery	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To test the non-inferiority of photodynamic therapy (PDT) to standard of care surgery by comparing the rate of tumor response after PDT to those observed after surgery, at 24 months post treatment.

SECONDARY OBJECTIVES:

1. To determine quality of life (QoL) at 6, 12, 18 and 24 months post PDT or surgery.

2. To assess the toxicity using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE Version 4.0).

TERTIARY OBJECTIVES:

1. Immune markers (T cells). II. To investigate the correlation of the diffuse reflectance optical spectroscopy with tumor response to PDT.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo standard of care surgery on day 1.

ARM II: Patients receive HPPH intravenously (IV) over 1 hour on day 0 and undergo PDT on day 1.

After completion of study treatment, patients are followed up every 3-4 months in year 1 and every 3-6 months in year 2.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Multicenter Phase II Study Using (2-1[Heyloxyethyl]-2-Devinylpyropheophorbide-a) (HPPH) With PDT Versus Standard of Care Surgery for Patients With T1/T2 N0 Squamous Cell Carcinoma of the Oral Cavity
• Actual Study Start Date: Mar 7, 2018
• Actual Primary Completion Date: Aug 1, 2021
• Actual Study Completion Date: Aug 6, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (surgery) Patients undergo standard of care surgery on day 1.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Procedure: Therapeutic Conventional Surgery; Undergo standard of care surgery
Experimental: Arm II (HPPH, PDT) Patients receive HPPH IV over 1 hour on day 0 and undergo PDT on day 1.	Drug: HPPH; Given IV; Other Names: Photochlor ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Photodynamic Therapy; Undergo PDT; Other Names: PDT Photoradiation Therapy ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment

Outcome Measures

Primary Outcome Measures

1. Rate of Tumor Response as Evaluated by Response Evaluation Criteria in Solid Tumors Version 1.1 [At 24 months]

   Objective tumor response will be tabulated overall.

Secondary Outcome Measures

1. Change in Quality of Life as Measured by the University of Washington Quality of Life Questionnaire Version 4 [Baseline up to 24 months]

   In the analysis of QoL simple data analyses will initially take place including individual participant-level profile plots and overall mean plots used to examining the mean structure. Formal statistical examination of longitudinal patterns will be done through the use of a mixed model. Once the model is fit, specific linear contrasts based on the estimated model parameters will be constructed and used to test hypotheses concerning between time points and between group comparisons

2. Adverse Events as Graded by CTCAE Version 4.0 Are Reported [Up to 30 days after administration of HPPH]

   The frequency of toxicities will be tabulated by grade.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

• Participants with previously untreated T1/T2 N0 squamous cell carcinoma of the oral cavity with or without extension to the oropharynx

• Histologically confirmed squamous cell carcinoma of the target tumor(s)

• Tumor thickness is 4 mm or less (measured clinically and/or by computed tomography [CT] or magnetic resonance imaging [MRI] scan)

• CT or MRI of the neck to confirm staging

• Tumor accessible for unrestricted illumination for photodynamic therapy (PDT) (accessibility as determined by the physician)

• Life expectancy of at least 12 months in the judgment of the physician

• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., 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 she is participating in this study, she should inform her treating physician immediately

• Participant or legal representative must understand the investigational nature of this study and sign an Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Those who have had chemotherapy or radiotherapy or targeted agents within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Those with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

• Those with porphyria or with known hypersensitivity to porphyrins or porphyrin-like compounds

• White blood cells (WBC) < 4,000

• Total serum bilirubin > 2 mg/dL

• Serum creatinine > 2 mg/dL

• Alkaline phosphatase (hepatic) or serum glutamic-oxaloacetic transaminase (SGOT) > 3 times the upper normal limit

• Diagnostic biopsy reveals perineural invasion (PNI) and/or lymphovascular invasion (LVI)

• 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

• Nodal disease as detected by clinical exam or CT

• Pregnant or nursing females

• Unwilling or unable to follow protocol requirements

• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

• Received an investigational agent within 30 days prior to enrollment

• Trismus or compromised airway

• Previous treatment in the target tumor area

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
2	University of Rocherster	Rochester	New York	United States	14642

Sponsors and Collaborators

• Roswell Park Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jon Chan, Roswell Park Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 22, 2021

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT03090412
• Other Study ID Numbers: I 33616; NCI-2017-00441; I 33616; P30CA016056
• First Posted: Mar 24, 2017
• Last Update Posted: Jun 2, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck

Study Results

Participant Flow

Arm/Group Title	Arm I (Surgery)	Arm II (HPPH, PDT)
Arm/Group Description	Patients undergo standard of care surgery on day 1. Quality-of-Life Assessment: Ancillary studies Therapeutic Conventional Surgery: Undergo standard of care surgery	Patients receive HPPH IV over 1 hour on day 0 and undergo PDT on day 1. HPPH: Given IV Laboratory Biomarker Analysis: Correlative studies Photodynamic Therapy: Undergo PDT Quality-of-Life Assessment: Ancillary studies
Period Title: Overall Study
STARTED	1	1
COMPLETED	1	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I (Surgery)	Arm II (HPPH, PDT)	Total
Arm/Group Description	Patients undergo standard of care surgery on day 1. Quality-of-Life Assessment: Ancillary studies Therapeutic Conventional Surgery: Undergo standard of care surgery	Patients receive HPPH IV over 1 hour on day 0 and undergo PDT on day 1. HPPH: Given IV Laboratory Biomarker Analysis: Correlative studies Photodynamic Therapy: Undergo PDT Quality-of-Life Assessment: Ancillary studies	Total of all reporting groups
Overall Participants	1	1	2
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	1 100%	1 50%
>=65 years	1 100%	0 0%	1 50%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	86	55	71
Sex: Female, Male (Count of Participants)
Female	1 100%	0 0%	1 50%
Male	0 0%	1 100%	1 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	1 100%	1 100%	2 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Rate of Tumor Response as Evaluated by Response Evaluation Criteria in Solid Tumors Version 1.1
Description	Objective tumor response will be tabulated overall.
Time Frame	At 24 months

Outcome Measure Data

Analysis Population Description

Due to PI departure and early termination with few patients, only the counts of events have been calculated and no testing was done

Arm/Group Title	Arm I (Surgery)	Arm II (HPPH, PDT)
Arm/Group Description	Patients undergo standard of care surgery on day 1. Quality-of-Life Assessment: Ancillary studies Therapeutic Conventional Surgery: Undergo standard of care surgery	Patients receive HPPH IV over 1 hour on day 0 and undergo PDT on day 1. HPPH: Given IV Laboratory Biomarker Analysis: Correlative studies Photodynamic Therapy: Undergo PDT Quality-of-Life Assessment: Ancillary studies
Measure Participants	1	1
No evidence of disease	1 100%	0 0%
Other	0 0%	1 100%

2. Secondary Outcome

Title	Change in Quality of Life as Measured by the University of Washington Quality of Life Questionnaire Version 4
Description	In the analysis of QoL simple data analyses will initially take place including individual participant-level profile plots and overall mean plots used to examining the mean structure. Formal statistical examination of longitudinal patterns will be done through the use of a mixed model. Once the model is fit, specific linear contrasts based on the estimated model parameters will be constructed and used to test hypotheses concerning between time points and between group comparisons
Time Frame	Baseline up to 24 months

Outcome Measure Data

Analysis Population Description

Due to PI departure with few patients, only the counts of events have been calculated and no testing was done..

Arm/Group Title	Arm I (Surgery)	Arm II (HPPH, PDT)
Arm/Group Description	Patients undergo standard of care surgery on day 1. Quality-of-Life Assessment: Ancillary studies Therapeutic Conventional Surgery: Undergo standard of care surgery	Patients receive HPPH IV over 1 hour on day 0 and undergo PDT on day 1. HPPH: Given IV Laboratory Biomarker Analysis: Correlative studies Photodynamic Therapy: Undergo PDT Quality-of-Life Assessment: Ancillary studies
Measure Participants	1	1
Outstanding Overall QoL	1 100%	0 0%
Very good to Outstanding Overall QoL	0 0%	1 100%

3. Secondary Outcome

Title	Adverse Events as Graded by CTCAE Version 4.0 Are Reported
Description	The frequency of toxicities will be tabulated by grade.
Time Frame	Up to 30 days after administration of HPPH

Outcome Measure Data

Analysis Population Description

Due to PI departure with few patients, only the counts of events have been calculated and no tabulation was done..

Arm/Group Title	Arm I (Surgery)	Arm II (HPPH, PDT)
Arm/Group Description	Patients undergo standard of care surgery on day 1. Quality-of-Life Assessment: Ancillary studies Therapeutic Conventional Surgery: Undergo standard of care surgery	Patients receive HPPH IV over 1 hour on day 0 and undergo PDT on day 1. HPPH: Given IV Laboratory Biomarker Analysis: Correlative studies Photodynamic Therapy: Undergo PDT Quality-of-Life Assessment: Ancillary studies
Measure Participants	1	1
Count of Participants [Participants]	1 100%	1 100%

Adverse Events

Time Frame	From administration of study drug or surgery until 30 days after receiving study drug or surgery
Arm/Group Title	Arm I (Surgery)		Arm II (HPPH, PDT)
Arm/Group Description	Patients undergo standard of care surgery on day 1. Quality-of-Life Assessment: Ancillary studies Therapeutic Conventional Surgery: Undergo standard of care surgery		Patients receive HPPH IV over 1 hour on day 0 and undergo PDT on day 1. HPPH: Given IV Laboratory Biomarker Analysis: Correlative studies Photodynamic Therapy: Undergo PDT Quality-of-Life Assessment: Ancillary studies
All Cause Mortality
	Arm I (Surgery)		Arm II (HPPH, PDT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Serious Adverse Events
	Arm I (Surgery)		Arm II (HPPH, PDT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		1/1 (100%)
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction	0/1 (0%)	0	1/1 (100%)	1
Vascular disorders
Haemorrhage	0/1 (0%)	0	1/1 (100%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Surgery)		Arm II (HPPH, PDT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)
Gastrointestinal disorders
Odynophagia	1/1 (100%)	1	0/1 (0%)	0
Tongue coated	1/1 (100%)	1	0/1 (0%)	0
Tongue exfoliation	0/1 (0%)	0	1/1 (100%)	1
Tongue oedema	0/1 (0%)	0	1/1 (100%)	1
General disorders
Face oedema	0/1 (0%)	0	1/1 (100%)	1
Injury, poisoning and procedural complications
Incision site pain	1/1 (100%)	2	0/1 (0%)	0
Thermal burn	0/1 (0%)	0	1/1 (100%)	1
Skin and subcutaneous tissue disorders
Photosensitivity reaction	0/1 (0%)	0	1/1 (100%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.