Phase 2a Study to Evaluate Suppression of Radiotherapy-induced Mucositis by TK112690
Study Details
Study Description
Brief Summary
Patients expected to receive a continuous course of radiation as single daily fractions of 2.0 Gy treatment with a cumulative radiation dose of 70 Gy. The radiation can be 2DRT, 3DRT,IMRT etc. Prior to each radiation treatment the patients will receive a one-hour infusion of TK-90 or equivalent TK-90 placebo depending on randomization. 6 Hours after the completion of TK-90 infusion or TK-90 placebo dose, the patients will receive another identical TK-90 or TK-90 placebo treatment depending on randomization. This treatment cycle will continue for 7 weeks. The TK112690 dose will be 45 mg/kg.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Patients expected to receive a continuous course of radiation as single daily fractions of 2.0 Gy treatment with a cumulative radiation dose of 70 Gy. The radiation can be 2DRT, 3DRT,IMRT etc. Prior to each radiation treatment the patients will receive a one-hour infusion of TK-90 or equivalent TK-90 placebo depending on randomization. 6 Hours after the completion of TK-90 infusion or TK-90 placebo dose, the patients will receive another identical TK-90 or TK-90 placebo treatment depending on randomization. This treatment cycle will continue for 7 weeks. The TK112690 dose will be 45 mg/kg.
-
24 patients will be randomized equally into 2 different groups: TK-90 treated or TK-90 placebo treated.
-
Screening must be completed within 2 weeks.
-
The treatment period for the study is 7 weeks.
-
Study follow-up will be scheduled post two weeks of completion of last dose of radiation or early termination through up to 4 weeks.
-
Blinding: The study will be partially blinded. The patient and investigator as well as site personnel will be blinded as to whether TK-90 or TK-90 placebo is administered. The CRO, sponsor, and site pharmacist will know whether the patient was administered active drug or TK-90 placebo.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TK112690 TK112690 treatment |
Drug: TK-112690
TK112690 treatment Pre & Post Radiation
|
| Placebo Comparator: Placebo TK112690 formulation |
Drug: Placebo
TK112690 Placebo treatment Pre & Post Radiation
|
Outcome Measures
Primary Outcome Measures
- Mucositis [7 weeks]
SOM (Severe Oral Mucositis) - Comparison of incidences of Grade 3 or 4 mucositis (WHO scale) in the treatment and placebo groups. Duration of SOM (Severe Oral Mucositis). Days patients suffer Grades 3 and 4 oral mucositis measured by WHO scale from the start of treatment. Calculate Number of days from the first occurrence of WHO Grade 3 or 4 oral mucositis through the first occurrence of non-severe (≤ Grade 2) without a subsequent instance of ≥ Grade 3 oral mucositis. Subjects with complete study follow-up for SOM who do not develop severe oral mucositis (grade 0-2) will be considered to have duration of 0 days.
Secondary Outcome Measures
- Secondary efficacy/outcome mucositis [7 weeks]
Mucositis status in the patients will also be evaluated using two different published and validated mucositis scales: NCI/CTCAE/mucositis, and PROMS. Comparison of WHO scale values of treated patients at each point of evaluation. NCI/CTCAE=National Cancer Institute/Common Terminology Criteria for Adverse Events and WHO=World Health Organization PROMS=Patient Reported oral Mucositis Symptom Scale As per WHO:Grade 0 to Grade 5 & NCI CTCAE: Grade 1 to Grade 5
- Incidence Adverse Events That Are Related to Treatment [7 Weeks]
Tolerance
Eligibility Criteria
Criteria
Inclusion Criteria:
- Participants must meet ALL of the following criteria at the time of screening unless otherwise specified:
-
Patient must sign study specific informed consent prior to study entry.
-
Male or Female patient aged 18 - 75 years.
-
Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) diagnosis of squamous cell carcinoma of the oral cavity (Refer Definition in 10.13.1), oropharynx or hypopharynx.
-
Patients must have at least 1 mucosal site of the oral cavity/oropharynx/hypopharynx mucosa assessable by visual transoral inspection that will receive cumulative radiation dose of 70 Gy.
Note: Unavoidable doses of at least 60 Gy, to include entrance, exit, and scatter doses, still constitutes planned radiation.
-
Patients with tumors of the larynx or hypopharynx are eligible only if it is anticipated that at least 1 index site in the oral cavity/oropharynx/hypopharynx mucosa (Refer section 10.13.1) will receive cumulative radiation dose of 70 Gy.
-
Selected Stage I to III or IVA-B per AJCC, Cancer Imaging Manual, 8th edition, at study entry, including no distant metastases other than non- metastatic SCCHN, based upon the following minimum diagnostic workup:
-
History/physical examination, including documentation of tobacco/alcohol use and current medications (including opioids/dosing), within 8 weeks prior to randomization.
-
Chest CT scan within 8 weeks prior to randomization.
-
MRI or CT scan with contrast of tumor site within 8 weeks prior to randomization.
-
Mucositis Grade ≤ 1 per WHO Scale and Xerostomia of Grade ≤ 2 per CTCAE version 5.0
-
ECOG Performance Status ≤ 2.
-
Adequate bone marrow function as per CTCAE V 5, defined as follows (within 2 weeks prior to randomization):
-
Absolute neutrophil count ≥ 1500cells/mm3 based upon CBC/differential obtained within 2 weeks prior to randomization.
-
Platelets ≥ 100,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to randomization.
-
Hemoglobin ≥ 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to randomization (Note: The use of transfusion or other intervention to achieve Hgb> 8.0 g/dl is acceptable).
-
Adequate hepatic function with bilirubin ≤ 1.5 x upper-normal limit (ULN), AST or ALT ≤3 x ULN within 2 weeks prior to randomization.
-
Adequate renal function with serum creatinine < 1.5 mg/dl and creatinine clearance (CrC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula. CrC male = [(140 - age) x (wt in kg)] / [(Serum Cr mg/dl) x (72)]. CrC female = 0.85 x (CrCl male) within 2 weeks prior to randomization.
-
Normal serum calcium or normal corrected serum calcium within 2 weeks prior to randomization; formula for corrected calcium if albumin valued is below normal range: Corrected calcium (mg/dl) = (4 - [Patient's albumin (g/dl)] x 0.8) + Patient's measured calcium (mg/dl).
-
Negative serum pregnancy test for women of childbearing potential.
-
Women of childbearing potential and male participants with female partners of childbearing potential must practice adequate contraception.
Exclusion Criteria:
Patients who meet any of the following criteria at the time of screening will be excluded:
-
Stage IVC (Any T, Any N, M1) per AJCC Cancer Staging Manual. 8th ed, or distant metastases at protocol study entry other than metastatic SCCHN.
-
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years.
-
Patients who have not fully recovered after prior surgery. (Patients who have had prior surgery and have fully recovered and patients who may have surgery in the future are eligible.).
-
Severe, active co-morbidity, defined as follows:
-
Symptomatic and/or uncontrolled cardiac disease, New York Heart Association Classification III or IV.
-
Transmural myocardial infarction within the last 6 months.
-
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of screening.
-
Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of screening.
-
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
-
Patients known to be sero-positive for human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV).
-
Collagen vascular disease, such as scleroderma.
-
Previous treatment with palifermin or other keratinocyte growth factors, such as velafermin or repifermin, within 28 days of randomization.
-
Any prohibited therapy 2 weeks prior to randomization (see Section 8.4).
-
Pregnancy, breast feeding or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.
-
Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
-
Known hypersensitivity study medication or excipients in the formulation.
-
Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sher-I-Kashmir Institute of Medical Sciences | Srinagar | Jammu & Kashmir | India | 190011 |
| 2 | Bangalore Medical college and Research Institute | Bangalore | Karnataka | India | 560002 |
| 3 | Saveetha Medical College and Hospita | Chennai | Tamil Nadu | India | 602105 |
| 4 | Apex Hospital | Varanasi | Uttar Pradesh | India | 221004 |
| 5 | Netaji Subhash Chandra Bose Hospital | Kolkata | West Bengal | India | 700094 |
Sponsors and Collaborators
- Tosk, Inc.
- SIRO Clinpharm Private Limited
Investigators
- Study Director: William Garland, Tosk, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CLP-2690-0004