Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Uterine Cervical Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Vinorelbine

Irinotecan

Pemetrexed

Topotecan

Cemiplimab

Topoisomerase I Inhibitors

Vinca Alkaloids

Folic Acid Antagonists

Antineoplastic Agents, Immunological

Intravenous (IV) administration every 3 weeks (Q3W)

IC chemotherapy options include:

1. Antifolate: Pemetrexed
2. Topoisomerase 1 inhibitor: Topotecan or Irinotecan
3. Nucleoside analogue: Gemcitabine
4. Vinca alkaloid: Vinorelbine

The only chemotherapy treatments allowed in the control arm are any of the 5 drugs that are listed as IC options above.

Investigator Choice (IC) Chemotherapy

Clinical Trial Management

The primary objective is to compare overall survival (OS) for patients with recurrent or metastatic cervical cancer who have histology of squamous cell carcinoma (SCC) and who have any eligible histology treated with either cemiplimab or investigator's choice (IC) chemotherapy.

The secondary objectives performed among SCC patients and among all eligible histologies (SCC and adenocarcinoma/adenosquamous carcinoma (AC) are:

* To compare progression-free survival (PFS) of cemiplimab versus IC chemotherapy
* To compare objective response rate (ORR) (partial response \[PR\] + complete response \[CR\]) of cemiplimab versus IC chemotherapy per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* To compare the duration of response (DOR) of cemiplimab versus IC chemotherapy
* To compare the safety profiles of cemiplimab versus IC chemotherapy by describing adverse events (AE)
* To compare quality of life (QOL) for patients treated with cemiplimab versus IC chemotherapy using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)

Study of Cemiplimab in Adults With Cervical Cancer

An Open-Label, Randomized, Phase 3 Clinical Trial of REGN2810 Versus Investigator's Choice of Chemotherapy in Recurrent or Metastatic Cervical Carcinoma

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact.

PFS was defined as the time from randomization to the date of the first documented tumor progression (radiographic) or death due to any cause. Participants who do not have a documented tumor progression or death were censored on the date of their last evaluable tumor assessment.

ORR was defined as the number of participants who achieved complete response (CR) or partial response (PR) as per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm) (\<1 centimeter \[cm\]). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

DOR was defined as the time from the date of first response (CR or PR) to the date of the first documented progressive disease (per RECIST 1.1) or death due to any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (\<1 cm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Participants who never progress while being followed was censored at the last valid tumor measurement. DOR was determined by Kaplan-Meier estimate.

EORTC QLQ-C30 is a 30-question tool used to assess the overall QoL in cancer participants. It consisted of 15 domains: 1 GHS/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the GHS/QoL, which are scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100. For the GHS/QoL and 5 functional scales a high score indicates better global health status/functioning and a negative change from baseline indicated less improvement. For the symptom scales, a high score indicates a higher level of symptoms, and a negative change from baseline indicated an improvement in symptoms.

An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs. Number of participants with TEAEs, serious TEAEs, and TEAEs leading to death were reported.

Laboratory parameters included hematology, electrolytes, chemistry (other), and liver function. Clinically significant abnormalities were determined by the investigator based on NCI-CTCAE Grade where Grade 1 = Mild, Grade 2 = moderate, Grade 3 = severe; Grade 4 = life threatening or disabling; Grade 5 = death. Participants with at least 1 lab abnormality Graded 3/4 in hematology, electrolytes, chemistry (other), or liver function reported.

Sanofi

Regeneron Pharmaceuticals

Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m\^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m\^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m\^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m\^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m\^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black or African American

Asian

American Indian or Alaska Native

Other

Unknown

Not Reported

Race/Ethnicity, Customized

The FAS included all randomized participants.

Clinical Trials Administrator

The full analysis set (FAS) included all randomized participants.

Overall Survival (OS)

Progression-free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Objective Response Rate (ORR) Assessed by Investigator Using RECIST 1.1

The FAS included all randomized participants with confirmed CR or PR

Duration of Response (DOR) Assessed Per RECIST 1.1

Overall: Change from Baseline of EORTC QLQ-C30 GHS/QoL

Overall: Changes from Baseline of EORTC QLQ-C30 Physical Functioning

Quality of Life (QoL): Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) of Global Health Status /Quality of Life (GHS/QoL) and Physical Functioning Scales

Participants with any TEAE

Participants with any Serious TEAE

Participants with any TEAE leading to Death

The safety analysis set (SAF) included all randomized participants who received any study drug.

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Death

Hematology (Grades 3/4)

Electrolytes (Grades 3/4)

Chemistry (Other) (Grades 3/4)

Liver Function (Grades 3/4)

The SAF included all randomized participants who received any study drug.

Number of Participants With New or Worsened Laboratory Results by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) Grade

Overall Study

Mouth and Tooth Diseases

Rare Diseases

Carcinoma in Situ

Cheilitis

Neoplasms, Squamous Cell

Mouth Diseases

Stomatognathic Diseases

Actinic Cheilitis

Topical ALA will be applied to the entire lip surface and allowed to incubate for 60 minutes plus or minus 30 minutes. Blue light at a wavelength of 405-420 nm will be used for treatment at a dose of 1000 seconds.

Topical placebo will be applied to the entire lip surface and allowed to incubate for 60 minutes plus or minus 30 minutes. Blue light at a wavelength of 405-420 nm will be used for treatment at a dose of 1000 seconds.

Day 1: Screening and consent for this study. If eligible, a scouting biopsy will be obtained at 1 cm from the clinical border of the SCC for confirmation of AC.

7-14 Days after consultation: PDT to all subjects in the study. If during treatment a subject requests to discontinue due to pain the treatment will be terminated.

3-5 weeks after consultation: return for assessment. At this visit, the assigned treatment may be repeated if the treatment site is adequately healed. Re-treatment will only occur if there is persistent actinic damage.

6-8 weeks after consultation: Mohs surgery will be performed as per routine. Following tumor removal a scouting biopsy will be taken at a site 1 cm from the wound site created by SCC removal. The current waiting time for non-urgent surgery is 8 weeks. Standard care is not being altered for subjects in the study, other then their receiving the PDT intervention.

Photographs may be taken at each subject visit.

PDT prior to Mohs surgery

Gary Rogers, M.D.

Our study is designed to evaluate the efficacy of photodynamic therapy (PDT) for treatment of actinic cheilitis (AC) and as an adjunct to Mohs surgery for squamous cell carcinoma (SCC) on the lips. This study will utilize an FDA approved PDT modality (DUSA, Inc., Wilmington, MA 01887) using topical 5-amino-levulinic acid (ALA) for photosensitization followed by exposure to a Blu-U light source emitting 405-420nm wavelength light.

BACKGROUND:

SCC of the lip is commonly surrounded by extensive AC, which may affect part or all of the lip vermillion. While Mohs surgical technique with complete margin control is the preferred treatment for SCC at critical locations such as the lip, this technique is complicated by surrounding AC. AC and SCC in situ at the tumor edge make it difficult to achieve margins clear of dysplasia and as a result extra tissue beyond the invasive SCC often needs to be excised to ensure that the entire tumor is removed.

Non-surgical treatments when used alone to treat SCC give lower cure rates than surgical removal, and thus are not recommended as they place the subject at risk for recurrence and metastatic disease. Although one study reported high SCC clearance rates with PDT alone (24/25 SCCs histologically cleared), recurrence of 2 SCCs occurred and a metastasis to a LN was seen in one patient. (Kubler et al.)

Given that PDT has been shown to have significant efficacy for actinic keratoses and actinic cheilitis but is inadequate as primary treatment of lip SCC, we propose that PDT may be a useful adjunct to surgical resection, allowing for less extensive surgery after the dysplasia is addressed with PDT and potentially a lower recurrence rate. Although imiquimod and 5-FU are also used to treat cutaneous dysplasia, many favor PDT treatment due to its greater tolerability, shorter healing time, and more predictable host response.

There is significant data on the efficacy of PDT for treatment of actinic keratoses (AKs) and PDT is now FDA approved for treatment of AKs. (Piacquadio et al). Data on PDT for treatment of AC is much more limited, but small studies and case reports do indicate successful treatment of AC with regimens utilizing either topical 5-aminolevulinic acid (5-ALA), or a similar compound, methylaminopentanoate (MAL). The largest study with 5-ALA reports complete clinical clearance in 13/19 patients treated with 1 to 3 treatments of ALA plus Pulsed-dye laser (Alexiades). Sotiriou et al report that with two PDT treatments 8/10 patients had complete clinical and histologic clearance (Sotiriou). Case reports indicate similar success (Kodama; Stender). Efficacy has also been shown with MAL PDT. One study found that with two sessions of MAL + red light PDT complete histologic/ clinical clearance was seen in 7/15 cases of AC and partial clearance was seen in an additional 7/15 (Berking et al). Smaller studies and case reports have shown even higher response rates without clinical recurrence during short-term follow-up (Rossi et al; Hauschild et al). We have chosen 5-ALA plus blue light for PDT treatment in this study because it is FDA approved for treatment of AKs and ALA is available in the United States.

Specific Aims:

1. To determine whether pre-operative treatment of the lips with ALA PDT can reduce the size of post-surgical defects (scars) in subjects with AC and lip SCC
2. To determine whether ALA PDT applied to the lips can effectively clear actinic cheilitis (AC) and SCC in-situ (SCC-is) of the lip.
3. To assess the tolerability of ALA PDT for treatment of AC and SCC-is of the lips

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Cemiplimab in Adults With Cervical Cancer	NCT03257267	Squamous Cell C... Recurrent or Me...	Cemiplimab Investigator Ch...	18 Years -	Regeneron Pharmaceuticals
Study of Cemiplimab in Adults With Cervical Cancer	NCT03257267	Squamous Cell C... Recurrent or Me...	Cemiplimab Investigator Ch...	18 Years -	Regeneron Pharmaceuticals
Study of Cemiplimab in Adults With Cervical Cancer	NCT03257267	Squamous Cell C... Recurrent or Me...	Cemiplimab Investigator Ch...	18 Years -	Regeneron Pharmaceuticals
Photodynamic Therapy to Treat Actinic Damage in Patients With Squamous Cell Carcinoma (SCC) of the Lip	NCT00868088	Actinic Cheilit... Squamous Cell C... Squamous Cell C... Photodynamic Th... Mohs Surgery	PDT prior to Mo...	18 Years -	Tufts Medical Center

Spots Global Cancer Trial Database for squamous cell carcinoma (scc)