Phase 2a Study to Evaluate Suppression of Radiotherapy-induced Mucositis by TK112690

Launched by TOSK, INC. · Dec 12, 2022

Keywords

ClinConnect 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.
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Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• * Participants must meet ALL of the following criteria at the time of screening unless otherwise specified:
• • 1. Patient must sign study specific informed consent prior to study entry.
• • 2. Male or Female patient aged 18 - 75 years.
• • 3. 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.
• • 4. 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.
• • 5. 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.
• 6. 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.
• • 7. Mucositis Grade ≤ 1 per WHO Scale and Xerostomia of Grade ≤ 2 per CTCAE version 5.0
• • 8. ECOG Performance Status ≤ 2.
• 9. 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).
• • 10. Adequate hepatic function with bilirubin ≤ 1.5 x upper-normal limit (ULN), AST or ALT ≤3 x ULN within 2 weeks prior to randomization.
• • 11. 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.
• • 12. 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).
• • 13. Negative serum pregnancy test for women of childbearing potential.
• • 14. 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:
• • 1. 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.
• • 2. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years.
• • 3. 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.).
• 4. 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).
• • 5. Collagen vascular disease, such as scleroderma.
• • 6. Previous treatment with palifermin or other keratinocyte growth factors, such as velafermin or repifermin, within 28 days of randomization.
• • 7. Any prohibited therapy 2 weeks prior to randomization (see Section 8.4).
• • 8. 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.
• • 9. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
• • 10. Known hypersensitivity study medication or excipients in the formulation.
• • 11. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.

Trial Officials