Persistent, Recurrent, or Metastatic Cervical CancerPhase 2ACCESS-INCT06670911

Low-dose Pembrolizumab Plus Chemotherapy for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer.

A Phase 2 study testing Low-dose Pembrolizumab Plus Chemotherapy (Paclitaxel plus Carboplatin or Cisplatin) in people with Persistent, Recurrent, or Metastatic Cervical Cancer, run by Instituto Nacional de Cancer, Brazil at 1 site in Brazil.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Persistent, Recurrent, or Metastatic Cervical Cancer
What is being tested?: Low-dose Pembrolizumab Plus Chemotherapy (Paclitaxel plus Carboplatin or Cisplatin)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 44 participants
Where: 1 siteBrazil
Study dates: 20 Feb 2025to Apr 2028
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

) Female participants aged 18 years and older
) Patients with persistent, recurrent, or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer, with PD-L1 CPS ≥ 1 expression, who have not received prior chemotherapy and are ineligible for curative surgery and/ or radiotherapy. Prior chemotherapy used as a radiosensitizer and completed at least 2 weeks before the scheduled date for C1D1 with resolution of all treatment-related toxicities is allowed. Adverse events due to prior treatments must be resolved to ≤ grade 1 or the participant's baseline. Neuropathy ≤ grade 2 or alopecia of grade ≤ 2 are eligible.
) Not pregnant or breastfeeding a ) Fertile-age women with the potential to become pregnant must agree to follow contraceptive guidance during treatment and for at least 120 days after the last dose of pembrolizumab and 210 days after the last dose of chemotherapy. Abstinence is acceptable if it is the participant's usual lifestyle and preferred contraception.
) The participant (or legal representative, if applicable) must provide written informed consent for the study. The participant may also provide consent for future biomarker research. However, the participant may participate in the main study without participating in future biomarker research.
) Have measurable disease according to RECIST 1.1 criteria, as assessed by the local investigator/radiologist. Lesions located in a previously irradiated area are considered measurable only if progression has been demonstrated.
) Have an archived tumor tissue sample (recurrent or metastatic cervical cancer) no older than 4 years or provide a biopsy of a previously unirradiated tumor lesion for prospective PD-L1 status determination, since only participants with PD-L1 expression CPS ≥ 1 will be included in the study.
) Performance Status/Eastern Cooperative Oncology Group (ECOG) of 0 to 1 within 7 days prior to C1D1
) Have adequate organ function, as indicated by the following laboratory values within 7 days prior to C1D1: a ) Absolute neutrophil count (ANC) ≥ 1,500/mcL; b ) Platelets ≥ 100,000/mcL; c ) Hemoglobin ≥ 9.0 g/dL - The criterion must be met without erythropoietin dependence and without transfusion in the last 2 weeks prior to Cycle 1 Day 1; d ) Creatinine ≤ 1.5 x upper limit of normal or creatinine clearance ≥ 60 mL/min for participants with creatinine levels > 1.5 x upper limit of normal - creatinine clearance (CrCl) should be calculated according to institutional standard using the Cockcroft-Gault formula; d ) Total serum bilirubin ≤ 1.5 x upper limit of normal; e ) AST and ALT ≤ 2.5 x upper limit of normal or ≤ 5 x upper limit of normal for participants with hepatic metastases; f ) International Normalized Ratio (INR) or Prothrombin Time (PT), Activated Partial Thromboplastin Time (aPTT) or Partial Thromboplastin Time (PTT) ≤ 1.5 x upper limit of normal, unless the participant is receiving anticoagulant, provided that PT or aPTT is within the therapeutic range for the intended use of anticoagulants.

Who cannot join

) Positive urine pregnancy test within 72 hours prior to C1D1. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
) Presence of known active central nervous system metastases and/or carcinomatous meningitis. Participants with known brain metastases may be included provided that the brain metastases have been previously treated (except with chemotherapy) and are radiographically stable. To demonstrate radiographic stability of previously treated brain metastases, a minimum of two post-treatment brain imaging evaluations are required: 1) The first brain image should be acquired after completion of the treatment of brain metastases. 2) The second image should be obtained during screening (i.e., within 28 days prior to the scheduled C1D1 date) and >4 weeks after the prior post-treatment brain image.Known brain metastases are considered active if any of the following criteria apply: a ) The brain image obtained during screening shows progression of existing metastases or the appearance of new lesions compared to brain images taken at least 4 weeks earlier b ) The neurological symptoms attributed to brain metastases have not returned to baseline; c) Steroid doses exceeding 10 mg of prednisone daily (or equivalent) were used to treat symptoms related to brain metastases within 28 days prior to the scheduled C1D1 date.
) Presence of other known malignancies within the past 3 years. Participants with basal cell carcinoma or squamous cell carcinoma of the skin who have undergone potentially curative therapy are not excluded.
) Having a diagnosis of immunodeficiency or being on chronic systemic steroid therapy (at doses greater than 10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the scheduled C1D1 date.
) Having an active autoimmune disease that has required systemic treatment within the past 2 years (i.e., with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) is permitted.
) History of non-infectious pneumonitis requiring steroid use.

Show all 20Show fewer

) Having an active infection requiring systemic therapy.
) Having a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required.
) Having a known history of hepatitis B (defined as positive hepatitis B surface antigen [HBsAg]) or known active hepatitis C virus (defined as detectable HCV RNA [qualitative]). No testing for hepatitis B and hepatitis C is required .
) Having a known history of active tuberculosis.
) Having received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or any other immune checkpoint inhibitor (CTLA-4, OX40, LAG3, etc.).
) Having received prior systemic chemotherapy for the treatment of advanced cervical cancer (chemotherapy used as a radiosensitizer and completed at least 2 weeks prior to the scheduled start date of cycle 1, day 1).
) Not having recovered adequately from toxicities and/or complications of major surgery prior to the scheduled start date of cycle 1, day 1.
) Having received radiotherapy within 2 weeks prior to the scheduled start date of cycle 1, day 1.
) Having received a live vaccine within 30 days prior to the scheduled start date of cycle 1, day 1 (measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), typhoid fever vaccine, etc.). Seasonal influenza vaccines are permitted.
) Having a contraindication or hypersensitivity to any component of carboplatin, paclitaxel, or cisplatin
) Currently participating or has participated in a study of an investigational agent or used an experimental device within 4 weeks prior to the scheduled start date of cycle 1, day 1.
) History of allogeneic solid organ/tissue transplantation.
) Having a known psychiatric disorder or substance abuse that may interfere with the study requirements.
) To have a history or current evidence of any condition, therapy, or laboratory abnormality that could confound the study results, interfere with participation, in the opinion of the treating investigator.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Andreia C Melo, PhD contact

552132072988

andreia.melo@inca.gov.br

Cecilia F da Silva, PhD contact

552132072988

cecilia.silva@inca.gov.br

Brazil1 site, 1 recruiting

Instituto Nacional de Cancer
Rio de Janeiro, Rio de Janeiro, 20231050
Andreia Melo, PhD, 55 2132072988, andreia.melo@inca.gov.br
Recruiting

Other trials in Brazil

About this study

Official title: A Phase II Trial of Low-dose Pembrolizumab Plus Chemotherapy for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer - ACCESS I

This is a phase II single-arm study of low-dose pembrolizumab (100mg, fixed-dose) plus chemotherapy in women aged 18 years or older with histologically confirmed persistent, recurrent, or metastatic cervical cancer who are ineligible for curative-intent treatment (surgery and/or radiation therapy) and who have not been previously treated with systemic chemotherapy, with the exception of chemotherapeutic agents used as radiosensitizers (cisplatin or carboplatin concurrent with radiation therapy).

Read the detailed description

This is a phase II single-arm study of low-dose pembrolizumab plus chemotherapy in women aged 18 years or older with histologically confirmed persistent, recurrent, or metastatic cervical cancer who are ineligible for curative-intent treatment (surgery and/or radiation therapy) and who have not been previously treated with systemic chemotherapy, with the exception of chemotherapeutic agents used as radiosensitizers (cisplatin or carboplatin concurrent with radiation therapy).

Participants must have measurable disease as defined by RECIST 1.1, as assessed by the local investigator/radiologist, and must provide a tumor tissue sample no older than 4 years for PD-L1 expression status determination. PD-L1 expression will be analyzed using the 22C3 antibody (Dako®) and classified according to the Composite Positive Score (CPS).

Treatment will consist of pembrolizumab 100mg administered by intravenous infusion plus chemotherapy every 3 weeks. Chemotherapy may be paclitaxel 175 mg/m2 plus carboplatin AUC 5 or paclitaxel 175 mg/m2 plus cisplatin 50 mg/m2 for patients not previously exposed to cisplatin. Both carboplatin and cisplatin should be administered immediately after paclitaxel. All study treatments should be administered on Day 1 (D1) of each 3-week treatment cycle. All participants should receive premedication to prevent severe hypersensitivity reactions according to local practice. Premedication should be administered after the pembrolizumab infusion and before chemotherapy.

During the treatment period, participants will have routine clinical visits for treatment administration, safety and well-being monitoring, and assessment of disease status changes.

Primary safety assessments will include physical examinations, vital signs, electrocardiography (ECG), hematology and biochemistry tests, thyroid function tests, and urinalysis. At each visit, adverse events will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 1 5.0. Study treatment doses may be interrupted or reduced (applicable only to chemotherapy) or discontinued in case of severe adverse events.

Imaging assessments will include computed tomography (CT) of the chest and magnetic resonance imaging (MRI) of the abdomen and pelvis. The first study imaging assessment will be performed at 9 weeks (63 days ± 7 days) from the date of Cycle 1 (C1) Day 1 infusion. Subsequent imaging should be performed every 9 weeks (63 days ± 7 days) until Week 54 and every 12 weeks (84 days ± 7 days) thereafter. Other imaging exams such as bone scintigraphy or brain imaging should be performed as clinically indicated.

Participants may interrupt or discontinue pembrolizumab and continue in the study. Similarly, participants may interrupt or discontinue chemotherapy and continue treatment with pembrolizumab.

Participants will receive study treatments until disease progression as defined by RECIST 1.1, unacceptable toxicities, intercurrent illness that precludes continued treatment, investigator's decision to withdraw the participant from treatment, withdrawal of consent, or administrative reasons requiring treatment discontinuation.

Participants may receive up to 6 cycles of paclitaxel-platinum (carboplatin or cisplatin). Participants may receive a maximum of 35 administrations of pembrolizumab (approximately 2 years). In the case of complete response (CR), study treatment may be discontinued at the investigator's discretion after the CR has been confirmed by radiographic imaging and the participant has received at least 2 cycles of pembrolizumab and to have completed a minimum of 8 total treatment cycles (approximately 24 weeks).

Participants who discontinue study treatment for reasons other than radiographic disease progression will be followed until documented disease progression by RECIST 1.1 criteria, initiation of new anticancer therapy, withdrawal of consent, loss to follow-up, or death.

After discontinuation of study treatment, participants may initiate subsequent anticancer treatments at the discretion of the treating physician and in accordance with local standard of care.

After verification of disease progression by RECIST 1.1 and/or initiation of subsequent oncological treatment, all participants will be followed up for overall survival (by telephone contact or in-person visits to the center) until withdrawal of consent, loss to follow-up, death, or until the study is completed or terminated early, whichever occurs first.

Symptomatic improvement is a recognized clinical benefit. Participants will complete the EuroQol EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-CX24 to assess quality of life.

The study will begin when the first participant signs the Informed Consent Form and will end when the last participant completes the final study-related call or visit, withdraws from the study, or is lost to follow-up (i.e., the participant cannot be contacted by the investigator).

Conditions: Persistent, Recurrent, or Metastatic Cervical Cancer
Being tested: Low-dose Pembrolizumab Plus Chemotherapy (Paclitaxel plus Carboplatin or Cisplatin)
Medical subject headings: Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Low-dose Pembrolizumab Plus Chemotherapy (Paclitaxel plus Carboplatin or Cisplatin)Drug
Patients will receive pembrolizumab 100mg IV every 3 weeks plus chemotherapy (paclitaxel 175 mg/m² + carboplatin AUC 5 or paclitaxel 175 mg/m² + cisplatin 50 mg/m² for cisplatin-naïve patients).

Study groups in NCT06670911
Study group	Role	What they receive
Low-dose Pembrolizumab Plus Chemotherapy	Experimental	pembrolizumab 100mg intravenous infusion plus chemotherapy every 3 weeks. Chemotherapy may consist of paclitaxel 175 mg/m² + carboplatina AUC 5 or paclitaxel 175 mg/m² + cisplatin 50 mg/m² for patients who have not been previously exposed to cisplatin. Receives: Drug: Low-dose Pembrolizumab Plus Chemotherapy (Paclitaxel plus Carboplatin or Cisplatin)

What is being measured

The primary outcome is the main question the study is designed to answer.

Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
Proportion of participants with complete or partial response per RECIST 1.1 as assessed by the investigator/radiologist patients with a confirmed complete or partial response by RECIST 1.1
Measured: Up to approximately 46 months

Secondary outcomes (8)

Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
For participants who demonstrate CR or PR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR per RECIST 1.1 as assessed by Investigator is presented.
documented progression or death in the absence of disease progression
Measured: Up to approximately 46 months
Number of Participants Who Experienced an Adverse Event (AE)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced an AE is presented.
Measured: Up to approximately 46 months
Quality of life during treatment
Assessment of Quality of Life Through Specific Questionnaires
Measured: Baseline (Cycle 1 Day 1: Predose) and up to approximately 46 months
PFS Per RECIST 1.1 as Assessed by Investigator in All Participants
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants is presented
Measured: Up to approximately 46 months
OS in All Participants
OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants is presented.
Measured: Up to approximately 46 months
Cost evaluation of adding pembrolizumab
To examine the direct cost consequences of incorporating pembrolizumab
Measured: Up to approximately 46 months
Number of Participants Who Experienced a Serious AE (SAE)
An SAE was defined as any untoward medical occurrence that, at any dose: a.) Resulted in death; b.) Was life-threatening; c.) Required inpatient hospitalization or prolongation of existing hospitalization; d.) Resulted in persistent or significant disability/incapacity; e.) Was a congenital anomaly/birth defect; f.) Other important medical events; h.) Was a new cancer (that is not a condition of the study) or i.) Was associated with an overdose. The number of participants who experienced an SAE is presented.
Measured: Up to approximately 46 months
Number of Participants Who Experienced an Immune-related AE (irAE)
AEs associated with pembrolizumab exposure may be a result of an immune response. These irAEs may occur shortly after the first dose or several months after the last dose of pembrolizumab treatment and may affect more than one body system simultaneously. For this study irAEs included, but were not limited to: -Pneumonitis; Diarrhea/Colitis; Aspartate transaminase (AST)/Alanine transaminase (ALT) elevation or Increased bilirubin; Type 1 diabetes mellitus or Hyperglycemia; Hypophysitis; Hyperthyroidism; Hypothyroidism; Nephritis and Renal dysfunction; and Myocarditis. The number of participants who experienced an irAE is presented.
Measured: Up to approximately 46 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Feb 2025Apr 2028

First posted1 Nov 2024
Study start20 Feb 2025
Primary completionApr 2026 (estimated)
Study completionApr 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Persistent, Recurrent, or Metastatic Cervical CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: This is a phase II, Simon 2-stage study. The null hypothesis is that the response rate with chemotherapy alone is 0.35 (35% according to published data from the INCA (10)), and the alternative hypothesis is that the true response rate is 0.55 (20% increase in response with the addition of pembrolizumab, as per the KEYNOTE-826 study. In stage I, a total of 14 patients will be treated. If there are 5 or fewer responses among these 14 patients, the study will be terminated early. Otherwise, an additional 30 patients will be treated in stage II, resulting in a total sample size of 44. If there are 21 or more responses among these 44 patients, we reject the null hypothesis and conclude that the treatment is promising. The type I error is 0.05 and the power is 0.8.
Masking: None (open label)
Enrolment: 44 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06670911
Sponsor's protocol ID: ACCESS-I
Acronym: ACCESS-I
Status last verified: Feb 2025
First submitted: 27 Aug 2024
Last updated: 24 Feb 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
PubMed 33538338
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763.
PubMed 36633525
Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019 Jan 12;393(10167):169-182. doi: 10.1016/S0140-6736(18)32470-X.
PubMed 30638582
Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, Nishimura S, Ushijima K, Takano M, Satoh T, Yoshikawa H. Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35. doi: 10.1200/JCO.2014.58.4391. Epub 2015 Mar 2.
PubMed 25732161
Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yanez E, Gumus M, Olivera Hurtado de Mendoza M, Samouelian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. doi: 10.1056/NEJMoa2112435. Epub 2021 Sep 18.
PubMed 34534429
Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R, Joshua AM, Patnaik A, Hwu WJ, Weber JS, Gangadhar TC, Hersey P, Dronca R, Joseph RW, Zarour H, Chmielowski B, Lawrence DP, Algazi A, Rizvi NA, Hoffner B, Mateus C, Gergich K, Lindia JA, Giannotti M, Li XN, Ebbinghaus S, Kang SP, Robert C. Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. JAMA. 2016 Apr 19;315(15):1600-9. doi: 10.1001/jama.2016.4059.
PubMed 27092830
Kang SP, Gergich K, Lubiniecki GM, de Alwis DP, Chen C, Tice MAB, Rubin EH. Pembrolizumab KEYNOTE-001: an adaptive study leading to accelerated approval for two indications and a companion diagnostic. Ann Oncol. 2017 Jun 1;28(6):1388-1398. doi: 10.1093/annonc/mdx076. No abstract available.
PubMed 30052728
Low JL, Huang Y, Sooi K, Ang Y, Chan ZY, Spencer K, Jeyasekharan AD, Sundar R, Goh BC, Soo R, Yong WP. Low-dose pembrolizumab in the treatment of advanced non-small cell lung cancer. Int J Cancer. 2021 Jul 1;149(1):169-176. doi: 10.1002/ijc.33534. Epub 2021 Mar 6.
PubMed 33634869

Interested in taking part?

Andreia C Melo, PhD

552132072988

andreia.melo@inca.gov.br

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

RecruitingPhase 3
A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) as First-line Maintenance Treatment of Cervical Cancer (MK-2870-036/TroFuse-036/GOG-3123/ENGOT-cx22)
Cervical Cancer
Active, not recruitingPhase 2
Nivolumab in Treating Patients With Persistent, Recurrent, or Metastatic Cervical Cancer
Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma
RecruitingPhase 3
A Study of GLS-010 Plus Platinum-containing Chemotherapy±Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer
Persistent, Recurrent, or Metastatic Cervical Cancer
RecruitingPhase 2/3
PD-1 (Programmed Death-1) Versus PD-L1 (Programmed Death-ligand 1) Immune Check Point Inhibitors Combined With Chemotherapy, With or Without Bevacizumab, In Patients With Metastatic, Persistent Or Recurrent Cervical Cancer
Metastatic Cervical Cancer, Persistent Cervical Cancer
Active, not recruitingPhase 2
SBRT and Atezolizumab in the Management of Recurrent, Persistent, or Metastatic Cervical Cancer
Cervical Cancer, Cervical Cancer Recurrent

All Persistent, Recurrent, or Metastatic Cervical Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Trial of Low-dose Pembrolizumab Plus Chemotherapy for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer - ACCESS I
ClinicalTrials.gov ID: NCT06670911
Acronym / sponsor ID: ACCESS-I / ACCESS-I
Conditions: Persistent, Recurrent, or Metastatic Cervical Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 44 participants (estimated)
Lead sponsor: Instituto Nacional de Cancer, BrazilOther government
Study start: 20 Feb 2025 (actual)
Primary completion: Apr 2026 (estimated)
Study completion: Apr 2028 (estimated)
First posted: 1 Nov 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

During the treatment period, participants will have routine clinical visits for treatment administration, safety and well-being monitoring, and assessment of disease status changes.

Participants may interrupt or discontinue pembrolizumab and continue in the study. Similarly, participants may interrupt or discontinue chemotherapy and continue treatment with pembrolizumab.

After discontinuation of study treatment, participants may initiate subsequent anticancer treatments at the discretion of the treating physician and in accordance with local standard of care.

Symptomatic improvement is a recognized clinical benefit. Participants will complete the EuroQol EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-CX24 to assess quality of life.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: This is a phase II, Simon 2-stage study. The null hypothesis is that the response rate with chemotherapy alone is 0.35 (35% according to published data from the INCA (10)), and the alternative hypothesis is that the true response rate is 0.55 (20% increase in response with the addition of pembrolizumab, as per the KEYNOTE-826 study. In stage I, a total of 14 patients will be treated. If there are 5 or fewer responses among these 14 patients, the study will be terminated early. Otherwise, an additional 30 patients will be treated in stage II, resulting in a total sample size of 44. If there are 21 or more responses among these 44 patients, we reject the null hypothesis and conclude that the treatment is promising. The type I error is 0.05 and the power is 0.8.

Arm	Type	Receives
Low-dose Pembrolizumab Plus Chemotherapy	Experimental	Drug: Low-dose Pembrolizumab Plus Chemotherapy (Paclitaxel plus Carboplatin or Cisplatin)pembrolizumab 100mg intravenous infusion plus chemotherapy every 3 weeks. Chemotherapy may consist of paclitaxel 175 mg/m² + carboplatina AUC 5 or paclitaxel 175 mg/m² + cisplatin 50 mg/m² for patients who have not been previously exposed to cisplatin.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

) Female participants aged 18 years and older
) Patients with persistent, recurrent, or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer, with PD-L1 CPS ≥ 1 expression, who have not received prior chemotherapy and are ineligible for curative surgery and/ or radiotherapy. Prior chemotherapy used as a radiosensitizer and completed at least 2 weeks before the scheduled date for C1D1 with resolution of all treatment-related toxicities is allowed. Adverse events due to prior treatments must be resolved to ≤ grade 1 or the participant's baseline. Neuropathy ≤ grade 2 or alopecia of grade ≤ 2 are eligible.
) Not pregnant or breastfeeding a ) Fertile-age women with the potential to become pregnant must agree to follow contraceptive guidance during treatment and for at least 120 days after the last dose of pembrolizumab and 210 days after the last dose of chemotherapy. Abstinence is acceptable if it is the participant's usual lifestyle and preferred contraception.
) The participant (or legal representative, if applicable) must provide written informed consent for the study. The participant may also provide consent for future biomarker research. However, the participant may participate in the main study without participating in future biomarker research.
) Have measurable disease according to RECIST 1.1 criteria, as assessed by the local investigator/radiologist. Lesions located in a previously irradiated area are considered measurable only if progression has been demonstrated.

Key exclusion criteria (20 listed)

) Positive urine pregnancy test within 72 hours prior to C1D1. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
) Presence of known active central nervous system metastases and/or carcinomatous meningitis. Participants with known brain metastases may be included provided that the brain metastases have been previously treated (except with chemotherapy) and are radiographically stable. To demonstrate radiographic stability of previously treated brain metastases, a minimum of two post-treatment brain imaging evaluations are required: 1) The first brain image should be acquired after completion of the treatment of brain metastases. 2) The second image should be obtained during screening (i.e., within 28 days prior to the scheduled C1D1 date) and >4 weeks after the prior post-treatment brain image.Known brain metastases are considered active if any of the following criteria apply: a ) The brain image obtained during screening shows progression of existing metastases or the appearance of new lesions compared to brain images taken at least 4 weeks earlier b ) The neurological symptoms attributed to brain metastases have not returned to baseline; c) Steroid doses exceeding 10 mg of prednisone daily (or equivalent) were used to treat symptoms related to brain metastases within 28 days prior to the scheduled C1D1 date.
) Presence of other known malignancies within the past 3 years. Participants with basal cell carcinoma or squamous cell carcinoma of the skin who have undergone potentially curative therapy are not excluded.
) Having a diagnosis of immunodeficiency or being on chronic systemic steroid therapy (at doses greater than 10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the scheduled C1D1 date.
) Having an active autoimmune disease that has required systemic treatment within the past 2 years (i.e., with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) is permitted.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Low-dose Pembrolizumab Plus Chemotherapy (Paclitaxel plus Carboplatin or Cisplatin)Patients will receive pembrolizumab 100mg IV every 3 weeks plus chemotherapy (paclitaxel 175 mg/m² + carboplatin AUC 5 or paclitaxel 175 mg/m² + cisplatin 50 mg/m² for cisplatin-naïve patients).	Drug	Low-dose Pembrolizumab Plus Chemotherapy

Primary outcome

Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
Time frame: Up to approximately 46 months
Proportion of participants with complete or partial response per RECIST 1.1 as assessed by the investigator/radiologist patients with a confirmed complete or partial response by RECIST 1.1

8 secondary outcomes

Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
Time frame: Up to approximately 46 months
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to approximately 46 months
Quality of life during treatment
Time frame: Baseline (Cycle 1 Day 1: Predose) and up to approximately 46 months
PFS Per RECIST 1.1 as Assessed by Investigator in All Participants
Time frame: Up to approximately 46 months
OS in All Participants
Time frame: Up to approximately 46 months
Cost evaluation of adding pembrolizumab
Time frame: Up to approximately 46 months
Number of Participants Who Experienced a Serious AE (SAE)
Time frame: Up to approximately 46 months
Number of Participants Who Experienced an Immune-related AE (irAE)
Time frame: Up to approximately 46 months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
Background: PubMed 33538338Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
Background: PubMed 36633525Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763.
Background: PubMed 30638582Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019 Jan 12;393(10167):169-182. doi: 10.1016/S0140-6736(18)32470-X.
Background: PubMed 25732161Kitagawa R, Katsumata N, Shibata T, Kamura T, Kasamatsu T, Nakanishi T, Nishimura S, Ushijima K, Takano M, Satoh T, Yoshikawa H. Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35. doi: 10.1200/JCO.2014.58.4391. Epub 2015 Mar 2.
Background: PubMed 34534429Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yanez E, Gumus M, Olivera Hurtado de Mendoza M, Samouelian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. doi: 10.1056/NEJMoa2112435. Epub 2021 Sep 18.
Background: PubMed 27092830Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R, Joshua AM, Patnaik A, Hwu WJ, Weber JS, Gangadhar TC, Hersey P, Dronca R, Joseph RW, Zarour H, Chmielowski B, Lawrence DP, Algazi A, Rizvi NA, Hoffner B, Mateus C, Gergich K, Lindia JA, Giannotti M, Li XN, Ebbinghaus S, Kang SP, Robert C. Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. JAMA. 2016 Apr 19;315(15):1600-9. doi: 10.1001/jama.2016.4059.
Background: PubMed 30052728Kang SP, Gergich K, Lubiniecki GM, de Alwis DP, Chen C, Tice MAB, Rubin EH. Pembrolizumab KEYNOTE-001: an adaptive study leading to accelerated approval for two indications and a companion diagnostic. Ann Oncol. 2017 Jun 1;28(6):1388-1398. doi: 10.1093/annonc/mdx076. No abstract available.
Background: PubMed 33634869Low JL, Huang Y, Sooi K, Ang Y, Chan ZY, Spencer K, Jeyasekharan AD, Sundar R, Goh BC, Soo R, Yong WP. Low-dose pembrolizumab in the treatment of advanced non-small cell lung cancer. Int J Cancer. 2021 Jul 1;149(1):169-176. doi: 10.1002/ijc.33534. Epub 2021 Mar 6.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Andreia C Melo, PhD contact

552132072988

andreia.melo@inca.gov.br

Cecilia F da Silva, PhD contact

552132072988

cecilia.silva@inca.gov.br

Andreia c Melo, PhD principal investigator

Instituto Nacional de Câncer José Gomes de Alencar da Silva - INCA

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Andreia C Melo, PhD (552132072988, andreia.melo@inca.gov.br), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator (time frame: Up to approximately 46 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06670911, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.