Phase II 177Lu-DOTATATE Study in Metastatic NPC With a Safety Run-in (SG-AAA-II-01)

National Cancer Centre, Singapore

Status and phase: Enrolling; Phase 2

Conditions: Metastatic Nasopharyngeal Cancer

Treatments: Radiation: 77 Lu-DOTA0-Tyr3-Octreotate

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05198479

SG-AAA-II-01

Details and patient eligibility

About

This study is the first phase II study of 177Lu-DOTA0-Tyr3-Octreotate in metastatic NPC. Patients whom have failed 2 or more lines of therapy or exhausted standard therapy and are avid on 68Ga-DOTATATE imaging will be eligible to receive up to 4 cycles of 177Lu-DOTA0-Tyr3-Octreotate. The primary outcome will be progression free survival at 6 months.

Full description

This would be an open label, single arm, single centre, phase II study designed to evaluate the efficacy of 177Lu-DOTA0-Tyr3-Octreotate in Metastatic NPC.

Patients will first need to go for a 68Ga-DOTATATE scan to determine if they are suitable for 177Lu-DOTA0-Tyr3-Octreotate therapy. A'Hern single stage phase II design (A'Hern, 2001) will be used for conducting the trial. The null hypothesis that the true PFS rate at 6 months is 10% will be tested against the alternate hypothesis of 25%. A total number of 25 patients will be recruited. If there are 5 or more patients who are alive and progression free among these 25 patients at 6 months, we reject the null hypothesis and claim that the treatment is promising.

The design controls the type I error rate at 9.8% and yields a power of 78.6% when the true PFS rate at 6 months is 25%. The first 5 patients will receive 180mCi of 177Lu-DOTA0-Tyr3-Octreotate for the first cycle followed by 200mCi for the remaining 3 cycles if there are no > Grade 2 toxicities after the first cycle. If there are >G2 toxicities, the remaining cycles will proceed at 180mCi. A safety review will be done after the first 5 patients. If there are no significant toxicities, the remaining patients will receive 200mCi for 4 cycles. If there are significant toxicities in patients receiving 200mCi for the 2nd to 4th cycle, the remaining patients will receive 180mCi for 4 cycles. If there are significant toxicities in patients receiving 180mCi for the 2nd to 4th cycle, the remaining patients will receive 160mCi for 4 cycles. Dosimetry scans will be done after each cycle of 177Lu-DOTA0-Tyr3-Octreotate at 1h and 96h. Safety and tolerability of 177LuDOTA0-Tyr3-Octreotate will be assessed for the duration of study treatment.

FDG PET/CT scan and 68Ga-DOTATATE scan will be performed at baseline and after cycle 1 (week 4) and cycle 4 (week 28). CT scans will be done at week 12, 24, then 3-monthly starting from week 40. 177Lu-DOTA0-Tyr3-Octreotate treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment is permitted. A treatment cycle is eight weeks (56 days) and will be repeated without therapy interruption for 4 cycles unless there is dose limiting toxicities.

Enrollment: 25 estimated patients

Sex: All

Ages: 21 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• a histologically confirmed diagnosis of NPC
• metastatic NPC that has failed two or more lines of therapy or exhausted standard therapy
• an Eastern Cooperative Oncology Group performance status of 0-2
• age 21-75 years, a life expectancy of more than 3 months
• no prior use of radionuclide therapy
• no prior radiotherapy to more than 25% of bone marrow
• less than 50% of bone marrow involved on 68Ga-DOTATATE scan
• Krenning score ≥ 3 and at least 75% concordance between 68Ga-DOTATATE scan and 18F-FDG PET scan
• at least 1 bidimensionally measurable (2 cm) site of disease.
• A wash-out period of at least 3 weeks from the last dose of prior chemotherapy is required before the administration of the first dose of 177Lu-DOTATATE.
• adequate hematologic, renal, and liver function using standard laboratory measurements
• no history of other malignancy, except treated basal cell and squamous cell skin carcinomas

Exclusion criteria

• Serum creatinine >120 μmol/L or 1.2 mg/dL, or a measured creatinine clearance (or measured glomerular filtration rate (GFR) using plasma clearance methods, not gamma camera-based) of <50 mL/min.
• Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <3x10^9/L (3000/mm3); platelets <75x10^9/L (75x10^3/mm3).
• Total bilirubin >3 x ULN.
• Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
• Pregnancy (see protocol Appendix 6).
• For female patients of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) and male patients, who are not surgically sterile or with female partners of childbearing potential: absence of effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel) as defined in Appendix 6.
• Peptide receptor radionuclide therapy (PRRT) at any time prior to enrolment in the study.
• Targeted surgery, radiotherapy (external beam), chemotherapy, embolization, interferons, mTOR-inhibitors or other investigational therapy within 3 weeks prior to enrolment in the study.
• Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrolment in the study. Patients with a history of brain metastases should have a head CT/MRI to document stable disease prior to enrolment in the study.
• Uncontrolled congestive heart failure (NYHA II, III, IV).
• Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.
• Any patient receiving treatment with short or long acting somatostatin analogs.
• Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study.
• Urinary incontinence.
• Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.
• Patients who have not provided a signed an informed consent form to participate in the study, obtained prior to the start of any protocol related activities.
• Patients who are unable to comply with relevant contact precautions post Lutetium therapy.
• Patients with a synchronous local nasopharyngeal recurrence, with prior high-dose irradiation to the primary tumour.
• Patients with active Hepatitis B (HBsAg positive) or Hepatitis C (HCV Ab positive) infection will be excluded.
• Patients with known history of Human Immunodeficiency Virus (HIV) will be excluded.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Arm 177 Lu-DOTA0-Tyr3-Octreotate

Experimental group

Description:

Treatment with 177Lu-DOTATATE consist of a cumulative dose of 23.68 - 29.6 GBq (640 - 800 mCi) 177Lu-DOTA0-Tyr3-Octreotate; Four administrations of 5.92 - 7.4 GBq (160 - 200 mCi) 177Lu-DOTA0-Tyr3-Octreotate; Concomitant amino acids will be given with each administration for kidney protection; 177Lu-DOTA0-Tyr3-Octreotate will be administered at 8±1-week intervals, which can be extended up to 16 weeks to accommodate resolving acute toxicity.

Treatment:

Radiation: 77 Lu-DOTA0-Tyr3-Octreotate