Ultrafractionated Radiation Therapy for Metastatic Cervical Cancer

• ClinicalTrials.gov Identifier: NCT05021237
• Recruitment Status: Recruiting
• First Posted: August 25, 2021
• Last Update Posted: April 5, 2023
• Sponsor: University of Texas Southwestern Medical Center
• Collaborator: Elekta Limited
• Information provided by (Responsible Party): Chika Nwachukwu, University of Texas Southwestern Medical Center

Study Description

Brief Summary:

To improve overall survival in patients with metastatic cervical cancer by loco-regional therapy with ultra-fractionated radiation therapy

Condition or disease	Intervention/treatment	Phase
Stage IV Cervical Cancer FIGO 2018; Adenosquamous Carcinoma of Cervix; Cervical Cancer; Metastasis	Radiation: Ultra-fractionated radiation therapy	Phase 2

Detailed Description:

The standard of care for treatment of locally advanced cervical cancer in the non-metastatic setting is a combination of radiation and chemotherapy. Radiotherapy for non-metastatic cervical cancer currently consists of radiation in the form of external beam delivered over 5-6 weeks of daily therapy followed by or interdigitated with intracavitary brachytherapy. Chemotherapy is used as a sensitizing agent with radiation and this is associated with substantial improvement in local control and overall survival. The treatment of metastatic cervical cancers is challenging, The standard of care for patients with metastatic disease is systemic therapy alone. The treatment of metastatic cervical cancers is challenging, with many patients developing resistance to platinum based chemotherapy and progressing through multiple lines of treatment. Although early stage cervical cancer is highly treatable with an excellent prognosis, recurrent and metastatic disease poses a significant treatment challenge. Several large clinical trials have demonstrated significant improvements in progression free and overall survival rates with the treatment of the local disease in other sites, eg head and neck and prostate cancer . These outcomes have generated optimism for aggressively treating local disease in the metastatic setting. Furthermore retrospective studies have demonstrated improvement in OS with treatment of the primary with radiation in women with metastatic cervical cancer. None of the studies have standardized their methods of treatment. In addition, treating metastatic patients with conventionally fractionated radiation treatment will prolong treatment time and can interrupt with systemic therapy which is critical for distant disease. With imaged-based ultrafractionated radiation, high doses can be delivered without inordinately large expansion margins and shortens treatment time. Moreover, studies have shown that the dose of radiation matters with higher doses associated with improved outcomes. These high doses levels can only be achieved with modern image guidance that limits expansion margins of radiation planning. Further pulsar technique allows for adaptation to the patient's tumor and anatomy and this process reduces the dose to the normal structures, thus minimizing serious toxicity in a metastatic population. There are no prospective trials of radiation in this setting. Currently, the standard of care remains cisplatin-based doublet therapy +/- avastin and this combination with radiation treatment has the potential to change outcomes and the could impact the management for this patient population

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Prospective Therapeutic Study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Safety Lead in Single Arm Phase II Study for Image Guided Ultrafractionated Radiation Therapy for Treatment of Metastatic Cervical Cancer
• Actual Study Start Date: February 1, 2022
• Estimated Primary Completion Date: October 2026
• Estimated Study Completion Date: October 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Safety Lead In; Six patients with will be enrolled as first dose of 8.5Gy. If 0 or 1 patient experiences dose-limiting toxicity (DLT) out of six patients, then study will move on to expansion phase. If two or more patients experience DLT out of six patients, 6 additional patients will be recruited to lower dose level of 8Gy	Radiation: Ultra-fractionated radiation therapy; Patients enrolled in this study are planned to receive systemic therapy. Imaging based Ultra-fractionated radiation therapy using a PULSAR technique, which is 5 pulses to gross tumor in pelvis.

Outcome Measures

Primary Outcome Measures :

1. To determine if image guided ultrafractionated radiation therapy in metastatic cervical cancer will improve overall survival outcomes [ Time Frame: 2 years ]
   Overall Survival will be assessed as the percent of patients surviving at each time point. Overall survival is defined as time from diagnosis till death.

Secondary Outcome Measures :

1. To assess the acute (< 90 days) grade > 3 toxicity. [ Time Frame: 90 days ]
   Toxicities will be defined as acute (< 90 days) grade > 3 GI and GU toxicity as assessed by CTCAE Version 5.0 (common terminology criteria for adverse events) from the commencement of image Guided Hypofractionated Radiation Treatment boost.
2. To evaluate the local-regional progression free survival (LR_PFS) [ Time Frame: 1 year ]
   The rate of local regional recurrence will be defined as disease recurrence in the pelvis and will be recorded on a time interval from start of radiation treatment to local progression or death. This will be evaluated as a median and rate up to 1 year post treatment.
3. QOL (qualify of life) [ Time Frame: 1 year ]
   To determine quality of life (QOL) in patients treated with radiation. Quality of life will be measured using the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) and EORTC QLQ-CX24 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-cervical cancer specific) questionnaires. The surveys will include the EORTC QLQ-C30 which assesses global health-related quality of life, the EORTC QLQ-CX24 which is targeted to patients with cervix cancer. Questionnaires will be scored according to published scoring guidelines. All patients on study will be asked to participate in this correlative quality of life component and will complete 2 surveys at 3 time points: baseline, 3 months post-treatment and 1-year post-treatment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Female only study
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. At least 18 years of age.
2. Ability to understand and the willingness to sign a written informed consent.
3. Newly diagnosed FIGO IVB cervical cancer with radiographic evidence of metastatic disease for whom systemic therapy is standard of care, who are within 6 months of systemic therapy treatment, OR
4. Patients with recurrent/metastatic disease with measurable disease in the pelvis for whom systemic therapy is standard of care, who are within 6 months of systemic therapy treatment.
5. Patients with brain metastasis are allowed as long as they are clinically stable and/or the mets are treated or are amenable to treatment with radiation and/or surgery.
6. Eastern Cooperative Group (ECOG) performance status of 0-3.
7. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting with the first radiation pulse through 90 days after the last fraction of radiation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Medically acceptable birth control (contraceptives) includes:

1) approved hormonal contraceptives (such as birth control pills, patch or ring; Depo-Provera, Implanon), or 2) barrier methods (such as a condom or diaphragm) used with a spermicide (a substance that kills sperm).

A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, 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)

Exclusion Criteria:

1. Prior radiation treatment to the pelvis.
2. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
3. Patients with active Inflammatory Bowel disease or Collagen vascular disease -SLE, scleroderma or on active immunosuppressant (exclusions per PI discretion).
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
5. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
6. Presence of brain metastases that are not amenable to treatment with radiation or surgery, or brain metastasis leading to clinical instability.

Contacts and Locations

Contacts

Contact: Sarah Neufeld; 214-645-8525; sarah.hardee@UTSouthwestern.edu

Contact: Liliana Robles; 214-645-8525; liliana.robles@utsouthwestern.edu

Locations

United States, Texas

UT Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75235

Contact: Chika. Nwachukwu, MD 214-645-8525 chika.nwachukwu@utsouthwestern.edu

Contact: Sarah Neufeld, MS 2146458525 sarah.hardee@utsouthwestern.edu

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Elekta Limited

Investigators

• Principal Investigator: Chika Nwachukwu, MD; UT Southwestern Medical Center

More Information

• Responsible Party: Chika Nwachukwu, Assitant Professor, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT05021237
• Other Study ID Numbers: 2021-0787
• First Posted: August 25, 2021
• Last Update Posted: April 5, 2023
• Last Verified: April 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Chika Nwachukwu, University of Texas Southwestern Medical Center:

Cervix

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Carcinoma, Adenosquamous; Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial