Clinical trial NCT02893982: High Dose Rate Brachyablation of Primary Liver Lesions
Official title: A Phase I Therapeutic Dose Escalation Study Using Percutaneous Image-Guided Navigation for High Dose Rate Brachyablation of Primary Liver Lesions
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Liver Cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2016-09-09
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objectives of this study are to demonstrate feasibility of an optimized, image-guided pre-planned workflow to deliver at least 25 Gy to the periphery of the target lesion while maintaining established dose constraints to normal tissues, and to determine the maximum tolerated dose (MTD) while evaluating treatment delivery, safety, and efficacy utilizing a pre-planned and optimized image-guided workflow for percutaneous HDR brachytherapy of liver lesions.

Detailed description: Primary endpoints of this protocol are to demonstrate feasibility of an optimized, image-guided pre-planned workflow to deliver at least 25 Gy to the periphery of the target lesion while maintaining established dose constraints to normal tissues, and then to determine the maximum tolerated dose (MTD) of navigated percutaneous interstitial HDR brachytherapy for liver lesions. Secondary endpoints include assessment of toxicity and oncologic outcome (primarily local control at the treated site) and exploratory endpoints will be supported by advanced imaging studies at the time of the treatment procedure.

The 25 Gy starting dose was chosen as it has been shown to be effective at controlling tumor, albeit with limited followup. The promising outcomes noted at that dose are predicated on actually delivering that dose, hence the feasibility endpoint for meeting the goal dose delivery. While the other primary endpoint will be toxicity so as to avoid exceeding the MTD, this trial will treat more patients at each level to better characterize both toxicity and efficacy within a dose level (the therapeutic window). The investigators will attempt to escalate to levels that modeling would predict to have durable local control approaching 100%.55 Dose escalation levels of 5 Gy were chosen to mirror other studies performed at this institution with SBRT

Eligibility criteria: Inclusion Criteria:

* Patients must have histologic or radiographic proof of a primary liver malignancy suitable for radiation therapy.
* Lesion size ≥ 3cm in maximum dimension.
* Predicted survival of \>6 months.
* KPS ≥ 60 (See Appendix B).
* Age ≥ 18 years old.
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  * Has not undergone a hysterectomy or bilateral oophorectomy; or
  * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
* Ability to understand and the willingness to sign a written informed consent.
* Formal evaluation by the Liver Tumor Program at UTSW: All patients should be fairly and prudently informed of their treatment options. To this end, all patients must be evaluated by the Liver Tumor Program at conference before brachytherapy treatment for discussion and consideration of other options for treatment of liver cancer including surgical resection.

Exclusion Criteria:

* Patients with a history of prior irradiation or other treatment to the liver or abdomen who after treatment on this protocol would have a cumulative dose to the liver or other normal tissues greater than the protocol defined constraints.
* Need or plans for concomitant antineoplastic therapy (including surgery, cryotherapy, radiofrequency ablation, chemo-embolization, conventionally fractionated radiotherapy, stereotactic body radiation therapy, and hepatic artery chemotherapy) for the protocol treated lesions except at progression. Adjuvant systemic therapy before and after the protocol therapy per section 4.4.1, and surgery or other ablative therapy is allowed for lesions appearing after enrollment to this protocol as per section 4.4.2 and 4.4.3 is allowed. At least 4 weeks must have passed since the last directed intervention to the protocol-treated lesion.
* Germ cell or hematologic malignancies.
* History of Crohn's Disease or Ulcerative Colitis.
* Active peptic ulcer disease for lesions within 5cm of the stomach.
* Underlying hepatic cirrhosis with Child-Pugh class B9 or C
* A major psychiatric illness which would limit understanding of the proposed protocol treatment and consent process.
* Men and women of reproductive potential may not participate unless they agree to use an effective contraceptive method.
* Pregnant or lactating women.
* Patients with parahepatic extension of disease with direct non-liver visceral involvement.
* Abnormal laboratory chemistries

  * Albumin \< 2.5
  * Alkaline Phosphatase \> 5 X upper limits of normal (ULN)
  * LT/AST \> 5 X ULN
  * Total bilirubin \> 5
* Abnormal complete blood count refractory to treatment. Any of the following:

  * Platelet count \< 75,000/ml
  * Hb level \< 8 gm/dl
  * ANC \< 500/ml
* Abnormal coagulation profile: INR \> 2 and/or PTT \> 80

  * Patients who are on anticoagulation medication that may not be safely held for the procedure (≥ 5 days for antiplatelet agents and warfarin; ≥ 24 hours for low-molecular weight heparin formulations) will be excluded.
* Contraindications to general anesthesia
* Subjects receiving any other investigational agents.

Primary outcomes:
measure: dosimetric coverage of liver lesions
timeFrame: 1 day
measure: maximum tolerated dose
timeFrame: 90 days
Secondary outcomes:
measure: severe toxicity
timeFrame: 30 days
measure: local control
timeFrame: 2 years
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Michael Folkert, MD
role: PRINCIPAL_INVESTIGATOR
References: