Study of Durvalumab With Chemoradiotherapy for Women With Locally Advanced Cervical Cancer (CALLA) (CALLA)

• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

This is a randomized, multi-center, double-blind, placebo-controlled, global, Phase III study to determine the efficacy and safety of durvalumab + Chemoradiotherapy versus Chemoradiotherapy alone as treatment in Women With Locally Advanced Cervical Cancer

Condition or disease	Intervention/treatment	Phase
Locally Advanced Cervical Cancer	Biological: Durvalumab; Drug: Cisplatin; Drug: Carboplatin; Radiation: external beam radiation therapy (EBRT) + brachytherapy	Phase 3

Detailed Description:

Women will be randomized in a 1:1 ratio to receive treatment with concurrent durvalumab + standard of care (SoC) or Placebo + Soc, followed by durvalumab/placebo maintenance for 24 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 714 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Multi-Center, Double-Blind, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With and Following Chemoradiotherapy Compared to Chemoradiotherapy Alone for Treatment in Women With Locally Advanced Cervical Cancer
• Actual Study Start Date: February 15, 2019
• Estimated Primary Completion Date: August 16, 2023
• Estimated Study Completion Date: April 16, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Durvalumab (intravenous infusion); durvalumab + standard of care concurrent chemoradiation therapy(SoC CCRT) followed by durvalumab monotherapy up to 24 months or until PD from the date of randomization	Biological: Durvalumab; IV infusion every 4 weeks; Drug: Cisplatin; Platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy; Drug: Carboplatin; Platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy; Radiation: external beam radiation therapy (EBRT) + brachytherapy; Radiation therapy per standard of care
Placebo Comparator: Placebo (matching placebo for intravenous infusion); placebo + standard of care concurrent chemoradiation therapy(SoC CCRT)	Drug: Cisplatin; Platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy; Drug: Carboplatin; Platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy; Radiation: external beam radiation therapy (EBRT) + brachytherapy; Radiation therapy per standard of care

Outcome Measures

Primary Outcome Measures :

1. The efficacy of durvalumab + SoC CCRT compared to placebo + SoC CCRT in terms of Progression-Free Survival (PFS) [ Time Frame: Estimated to be from the time of randomization up to 4.5 years ]
   Progression-Free Survival is defined as the time from randomization until the date of objective disease progression (RECIST 1.1 or histopathologic evidence) or death (by any cause in the absence of progression).

Secondary Outcome Measures :

1. The efficacy of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by the time from the date of randomization until death due to any cause in terms of Overall Survival (OS) [ Time Frame: Estimated to be from the time of randomization up to 5 years ]
   The analysis of OS will be based on time from date of randomization until the date of death by any cause
2. The efficacy of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by proportion of patients with a complete response at the first tumor assessment after chemoradiotherapy in terms of Complete Response (CR) rate [ Time Frame: Estimated to be up to 20 weeks ]
   The analysis of CR rate will be based on investigator assessments using RECIST 1.1 or histopathologic assessment of local disease progression.
3. The efficacy of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by the number (%) of patients with at least one visit response of Complete Response (CR) or partial response (PR) in terms of Objective Response Rate (ORR) [ Time Frame: Estimated to be up to 4.5 years ]
   The analysis of ORR will be based on investigator assessments using RECIST 1.1 or histopathologic assessment of local disease progression.
4. The efficacy of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by time from detection of CR until the date of disease progression in terms of Duration of Response (DoR) in patients with a Complete Response (CR) [ Time Frame: Estimated up to 4.5 years ]
   The analysis of DoR in patients with a CR will be based on investigator assessments using RECIST 1.1 or histopathologic confirmation of local disease progression.
5. Disease-related symptoms and health related quality of life (HRQoL) in patients treated with durvalumab + SoC CCRT compared with placebo + SoC CCRT as assessed by the change from baseline in disease-related symptoms and HRQoL [ Time Frame: Estimated up to 4.5 years ]
   The analysis of disease-related symptoms and HRQoL based on European Organization for Research and Treatment of Cancer (EORTC) core cancer instrument (EORTC QLQ-C30)
6. Disease-related symptoms and health related quality of life (HRQoL) in patients treated with durvalumab + SoC CCRT compared with placebo + SoC CCRT as assessed by the change from baseline in disease-related symptoms and HRQoL [ Time Frame: Estimated up to 4.5 years ]
   The analysis of disease-related symptoms and HRQoL based on European Organization for Research and Treatment of Cancer (EORTC) supplemental cervical cancer module (EORTC CX24).

Other Outcome Measures:

1. Number of participants with adverse events as assessed by Common Toxicity Criteria for Adverse Events (CTCAE v5.0) [ Time Frame: Estimated to be up to 2.5 years ]
   Type, frequency and severity of adverse events (including those from the pre- and post-treatment periods) will be listed according to CTCAE v5.0
2. The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by electrocardiograms (ECGs) [ Time Frame: Estimated to be up to 2.5 years ]
   Resting 12-lead ECGs will be assessed by QTcF interval (ms).
3. The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(pulse rate) in beats per minute. [ Time Frame: Estimated to be up to 2.5 years ]
   Pulse rate will be evaluated according to the schedule of assessments.
4. The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(temperature) in degree Celsius. [ Time Frame: Estimated to be up to 2.5 years ]
   Temperature will be evaluated according to the schedule of assessments.
5. The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(respiration rate) in breaths per minute. [ Time Frame: Estimated to be up to 2.5 years ]
   Respiration rate will be evaluated according to the schedule of assessments.
6. The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by vital signs(blood pressure). [ Time Frame: Estimated to be up to 2.5 years ]
   Blood pressure will be evaluated according to the schedule of assessments.
7. The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by abnormality in clinical chemistry. [ Time Frame: Estimated to be up to 2.5 years ]
   Clinical chemistry will be assessed by liver function(Alanine aminotransferase, Aspartate aminotransferase, albumin, total bilirubin), kidney function (e.g. Urea, Creatinine) and endocrine function(TSH, T3 free,T4 free).
8. The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by abnormality in hematology(cells/L). [ Time Frame: Estimated to be up to 2.5 years ]
   Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count.
9. The safety and tolerability of durvalumab + SoC CCRT compared to placebo + SoC CCRT as assessed by abnormality in hematology(g/L). [ Time Frame: Estimated to be up to 2.5 years ]
   Hematology will be assessed by haemoglobin.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 130 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Female: only female participants are being studied
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

For inclusion in the study, patients should fulfill the following criteria:

1. Female
2. Aged at least 18 years
3. Documented evidence of cervical adenocarcinoma or squamous carcinoma FIGO Stage IB2-IIB Node positive or IIIA-IVA any node
4. No prior chemotherapy or radiotherapy for cervical cancer
5. WHO/ECOG performance status of 0-1
6. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion at baseline.

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

1. Diagnosis of small cell (neuroendocrine) histology cervical cancer
2. Intent to administer a fertility-sparing treatment regimen
3. Undergone a previous hysterectomy
4. Evidence of metastatic disease per RECIST 1.1 including lymph nodes ≥15 mm (short axis) above the L1 cephalad body or outside the planned radiation field.
5. History of allogeneic organ transplantation
6. Active or prior documented autoimmune or inflammatory disorders
7. Uncontrolled intercurrent illness
8. History of another primary malignancy and active primary immunodeficiency

Contacts and Locations

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

  Show 129 Study Locations

Sponsors and Collaborators

AstraZeneca

Investigators

• Study Director: Mark Lanasa, M.D., Ph.D.; AstraZeneca
• Principal Investigator: Bradley Monk, M.D; University of Arizona, Arizona, USA

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03830866 History of Changes
• Other Study ID Numbers: D9100C00001
• First Posted: February 5, 2019
• Last Update Posted: July 16, 2019
• Last Verified: July 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by AstraZeneca:

Durvalumab; Chemoradiotherapy; Locally Advanced Cervical Cancer

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Carboplatin; Durvalumab; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immunologic Factors; Physiological Effects of Drugs