Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Cisplatin

Durvalumab

Antineoplastic Agents, Immunological

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

placebo + standard of care concurrent chemoradiation therapy(SoC CCRT)

Platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy

For patients enrolled under CSP v2 and prior - platinum based Standard of Care Chemotherapy administered concurrent with radiation therapy

external beam radiation therapy (EBRT) + brachytherapy

Urban Scheuring, M.D., Ph.D.

Bradley Monk, M.D

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

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.

Female: only female participants are being studied

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

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

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

PFS defined as time from date of randomisation until date of tumour progression or death by any cause, regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression

Number of Participants with Overall Survival (OS) where OS was defined as the time from the date of randomisation until death by any cause

Time from the date of randomisation until death by any cause

Percentage of evaluable patients with an Investigator-assessed visit response of complete response (CR) or partial response (PR). CR defined as disappearance of all target and non-target lesions and no new lesions. PR defined as \>= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion

Percentage of evaluable patients with an overall visit response of Complete Response (disappearance of all target and non-target lesions)

Time from date of first documented CR until date of documented progression or death in the absence of progression. For patients who did not progress their DoR was their Progression-free survival censoring time

AstraZeneca

There were 385 subjects randomised to each of Durva + SoC CCRT and Placebo + SoC CCRT respectively (Full Analysis Set), however 1 of the subjects allocated to Placebo + SoC CCRT did not receive treatment (resulting in 384 in the Safety Analysis Set). Hence, for Placebo + SoC CCRT, the Total number at risk for all-cause mortality = 385 while the Total # at Risk by any Serious Adverse Event = 384 and the Total # at Risk by any Other Adverse Event = 384

Durvalumab 1500mg IV infusion every 4 weeks plus Standard of Care (SoC) concurrent chemoradiotherapy (CCRT) (chemotherapy for 5 weeks plus external beam radiotherapy and brachytherapy)

Durvalumab + SoC CCRT

Placebo IV infusion every 4 weeks plus Standard of Care (SoC) concurrent chemoradiotherapy (CCRT) (chemotherapy for 5 weeks plus external beam radiotherapy and brachytherapy)

Placebo + SoC CCRT

Total

Age, Continuous

Sex: Female, Male

White

Black or African American

Asian

American Indian or Alaska Native

Other

Race/Ethnicity, Customized

Global Clinical Lead

Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression

Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression, PD-L1 Expression >= 1%

Overall Survival (Count)

Overall Survival (Duration)

Objective Response Rate (ORR)

Complete Response Rate

Duration of Response (DoR) in Patients With Complete Response (CR)

Overall Study

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Patients receive 1 cycle of cisplatin and nab paclitaxel combined neoadjuvant chemotherapy and subsequent 2 cycles of camrelizumab combined neoadjuvant chemotherapy. Based on the tumor size as indicated by MRI, patients who achieve complete response or partial response (CR/PR，RECIST v1.1) will undergo open radical hysterectomy and pelvic lymph node dissection. Patients who show stable disease or progression (SD/PD，v1.1) will proceed directly to concurrent chemoradiotherapy (CCRT).

Pelvic EBRT + concurrent platinum-containing chemotherapy + brachytherapy

Camrelizumab is administered at 200mg, q3w (second and third cycles) before radical surgery

Camrelizumab

Cisplatin：75-80mg/m2, D1-D2，q3w (3 cycles)，intravenous infusion, administered at a rate of 1mg/min.

Nab paclitaxel: 260 mg/m2，D1，q3w （3 cycles），intravenous infusion, administered over 30min.

Nab paclitaxel

Radical surgery

Chemotherapy administered concurrent with radiation therapy，cisplatin 40 mg/m2 IV once per week (QW) for 5 weeks

Kezhen Li

Jing Chen

Gang Chen

Ding Ma

It is a prospective, open-label, randomized, controlled phase II/III clinical trial in which patients with PD-L1-positive FIGO stage IB3, IIA2 and IIB（tumors \>4 cm in diameter）will be enrolled and randomly divided into the neoadjuvant chemoimmunotherapy plus surgery group and the CCRT group.

Cervical cancer is the most common gynecological malignancy in China, with locally advanced cervical cancer (LACC) accounting for approximately 37% of cases. Currently, the recommended standard of care for LACC according to international guidelines is concurrent chemoradiotherapy (CCRT). However, the impacts of radiation therapy on patients' quality of life are increasingly being recognized. Additionally, 23.3% to 34.4% of patients still face recurrence or metastasis after treatment, and the 5-year overall survival rate remains around 75%.

Neoadjuvant chemotherapy (NACT) is a chemotherapy regimen used prior to surgery for LACC. NACT followed by radical surgery has a similar overall survival compared to CCRT, but the disease-free survival is relatively lower with NACT. Moreover, 9.8% to 30.6% of patients show poor response to NACT, and over 30% of patients require postoperative adjuvant therapy. These issues significantly limit the application of NACT in LACC.

In recent years, immunotherapy has made significant progress in advanced or recurrent cervical cancer. A phase II clinical trial of combination of PD-1 inhibitors and neoadjuvant chemotherapy showed significant anti-tumor activity and safety. Therefore, based on the preliminary results, this project aims to conduct a multicenter, prospective, randomized controlled clinical trial to further confirm the value of neoadjuvant immunotherapy combined with surgery in LACC. It will be compared with the standard CCRT regimen to explore the differences in clinical efficacy and adverse events between the two groups, providing high-level evidence for the application of neoadjuvant immunotherapy in cervical cancer.

Neoadjuvant Chemoimmunotherapy Versus Concurrent Chemoradiotherapy for LACC

Neoadjuvant Chemoimmunotherapy Combined With Surgery Versus Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer: a Multicenter Randomized Controlled Clinical Trial

PFS is defined as the time from randomisation to tumor progression, postoperative relaspse or metastasis, or death, which occur first.

The proportion of patients who had either complete response or partial response, assessed by independent central reviewers according to RECIST, version 1.1.

OS is defined as the time from randomisation to death.

Proportion of patients undergoing radical surgery for neoadjuvant chemoimmunotherapy plus surgery group

Pathologic complete response (pCR) refers to the absence of invasive/in situ cancer in the cervical and/or lymph nodes.

Intraoperative bleeding, vascular injuries, bladder injuries, rectal injuries, and ureteral injuries were measured by the need for suture repair; occlusive nerve injuries were measured by complete severance, and vascular injuries required documentation of the site of injury. Postoperative complications included: cervical stenosis, cervical insufficiency, ureteral/bladder/rectal/vaginal fistula, internal hemorrhage, pelvic infection, lymphocyst, lymphatic fistula, lower extremity edema, lower extremity venous thrombosis, urinary retention, nerve injury, and bowel obstruction.

The incidence of adverse evetns, severe adverse events; surgery related safety.

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=not at all to 4=very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in physical function (EORTC QLQ-C30 Items 1-5) score will be presented.

The EORTC QLQ-CX24 is a questionnaire that rates the symptoms common to women with cervical cancer and evaluates the impact of disease and/or treatments. The 24 items use a 4-point scale (1=not at all to 4=very much) and are classified into 3 multi-item scales, 11 items with symptom experience, 3 items with body image, and 4 items with sexual/ vaginal functioning. The other items of the questionnaire are lymphedema, peripheral neuropathy, menopausal symptom, sexual worry, sexual activity, and sexual enjoyment. The change from baseline in EORTC QLQ-CX24 score will be presented.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Durvalumab With Chemoradiotherapy for Women With Locally Advanced Cervical Cancer (CALLA)	NCT03830866	Locally Advance...	Durvalumab Cisplatin Carboplatin external beam r...	18 Years - 130 Years	AstraZeneca
Neoadjuvant Chemoimmunotherapy Versus Concurrent Chemoradiotherapy for LACC	NCT06288373	Cervical Cancer Locally Advance... Concurrent Chem... Neoadjuvant Che...	Camrelizumab Cisplatin Nab paclitaxel Radical surgery external beam r... Cisplatin	18 Years - 70 Years	Tongji Hospital

Spots Global Cancer Trial Database for external beam radiation therapy (ebrt) + brachytherapy