Clinical trial for patients with serious head and neck cancer

Phase 1

Conditions: Head and neck squamous cell carcinoma (HNSCC)
MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-003959-37-CZ

Lead Sponsor: anoCarrier Co, Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 136

Inclusion Criteria

1. Be willing and able to provide written informed consent for the trial.
2. Males or females aged =18 years at screening.
3. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
4. Have histologically- or cytologically-confirmed HNSCC.
5. Have recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx that is considered incurable by local therapies
6. Must have received = 150mg/m2 of a total dose of cisplatin or 2 cycles of carboplatin AUC5 (maximum carboplatin dose per cycle 750mg)
7. Prior platinum failure as defined by
a. Disease progression confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) scans using RECIST 1.1 criteria at any time during or after treatment with a platinum agent or a platinum-containing regimen for recurrent/metastatic disease
b. Recurrence/progression confirmed by CT or MRI imaging scans using RECIST 1.1 criteria < 6 months of prior modal therapy using a platinum agent or a platinum-containing regimen for locally advanced setting,
c. Recurrence/progression = 6 months of prior modal therapy in locally advanced HNSCC can be accepted only if subjects have received a further platinum containing regimen for recurrent and metastatic stage of disease and have progressed during or after this regimen.
8. Have a life expectancy of > 3 months
9. Have radiographically measurable disease based on RECIST 1.1
10. Have adequate bone marrow reserve, defined as:
a. Absolute neutrophil count = 1.5 × 109/L,
b. Platelet count = 100 × 109/L, and
c. Hemoglobin = 10 g/dL (transfusion is allowed to achieve = 10 g/dL)
11. Have adequate liver function, defined as
a. Total serum bilirubin = 1.5 × the upper limit of normal (ULN),
b. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.0 × ULN or < 5.0 × ULN in case of documented hepatic metastasis
c. Serum albumin = 3.5 g/dL
12. Have prothrombin time within normal limits
13. Have adequate renal function, using the Cockcroft method: Glomerular filtration rate = 60 mL/min
14. Have results from central laboratory testing of HPV (defined as p16 IHC testing using CINtec p16 Histology assay and a 70% cutoff point)
15. Have provided tissue for PD-L1 biomarker analysis from a newly obtained core, excisional biopsy or an archived specimen. Repeat samples may be required if adequate tissue is not provided or for indeterminate results.
Note: If emerging data indicate a high concordance in PD-L1 expression scores between newly obtained and archival samples, archived samples may be acceptable.
16. Female subjects of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication. A urine test can be considered if a serum test is not appropriate.
17. Female subjects of childbearing potential must be willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study therapy according to local standard of care
Note: Abstinence is acceptable if this is the established and preferred contraception for the subject
18. Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy according to local standard of care
Note: Abstinence is acceptable if this is the establis

Exclusion Criteria

1. Subjects with carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary origination, squamous cell carcinoma that originates from the skin and salivary gland or paranasal sinus, non-squamous histologies.
2. Have disease that is suitable for locoregional treatment administered with curative intent or refuses curative intent.
3. Have more than 15% body weight loss due to the underlying condition in the last 3 months from signing of informed consent in Part 1 of the study and from randomization in to Part 2.
4. Are currently participating in or have participated in a study of an investigational agent or are using an investigational device within 4 weeks prior to the first dose of trial treatment.
5. Have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks since the last dose of trial treatment the previous investigational agent or device
6. Were previously treated with 3 or more lines of systemic therapies administered for recurrent and/or metastatic disease.
7. Were diagnosed and/or treated additional malignancy within 5 years of randomization, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, and/or curatively-resected in situ cervical and/or breast carcinoma
8. Have 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.
9. Subjects with a condition requiring systematic treatment with corticosteroids (> 10mg daily prednisone equivalents) within 14 days prior to the first dose of study treatment.
10. Have had prior anti-cancer treatment or radiation therapy within 4 weeks prior to study Day 1 or who have not recovered (i.e., = Grade 1 or at baseline) from AEs due to previously administered treatment more than 4 weeks earlier (i.e., monoclonal antibody [mAb], cetuximab, or any other cytotoxic drugs). (Subjects with = Grade 2 alopecia are an exception to this criterion and may qualify for the study.)
11. Had a prior allogenic organ or tissue transplant
12. Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
13. Have peripheral sensory neuropathies (including hearing loss) and motor neuropathies >/= grade 2, in the opinion of the investigator.
14. Have uncontrolled hypertension, defined as systolic blood pressure >180 mmHg and/or diastolic blood pressure >130 mmHg under resting conditions.
15. Have experienced any of the following within the 6-month period prior to screening: unstable angina pectoris, cerebrovascular accident, transient ischemic attack, uncontrolled congestive heart failure (New York Heart Association > class II) cardiac failure with known ejection fraction less than 40%, or cardiac arrhythmia (subjects with well-controlled cardiac arrhythmia on stable doses of medication are permitted).
16. Have an active autoimmune disease requiring systemic treatment within the past 3 m

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Part 1(Phase IIa):<br>To assess dose-limiting toxicities (DLTs), and to determine the optimal dose in order to establish the recommended Phase IIb (RPIIb) dose for the combination of NC-6004 plus pembrolizumab.<br><br>Part 2 (Phase IIb):<br>To compare progression-free survival (PFS) between NC-6004 plus pembrolizumab and pembrolizumab alone.;Secondary Objective: To evaluate the safety and tolerability of NC-6004 when combined with pembrolizumab.<br>To compare OS between NC-6004 plus pembrolizumab and pembrolizumab alone.<br>To compare tumor response between NC-6004 plus pembrolizumab and pembrolizumab alone.;Primary end point(s): - To establish the RPIIb dose.<br>- To determine the PFS by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in eligible subjects after treatment with NC-6004 plus pembrolizumab and pembrolizumab alone.;Timepoint(s) of evaluation of this end point: RP2D will be determined in March 2020 PFS in PIIb portion will be available in March 2022.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Overall response rate (ORR)<br>• Complete response (CR)/ Partial response (PR)<br>• Stable disease (SD)<br>• Duration of response (DOR)<br>• Time to response (TTR)<br>Pharmacokinetics endpoints in phase IIa<br>;Timepoint(s) of evaluation of this end point: ORR will be assessed by performing study imaging every 6 weeks after the first dose of study treatment.<br>Safety data as well as PK data of PIIa portion will be available in March 2019. OS or other efficacy data of PIIb will be available in March 2022.

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