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

NCT06670911 | Recruiting Phase 2

• 1 other identifier: ACCESS-I
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Persistent, Recurrent, or Metastatic Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  Up to approximately 46 months

Secondary Outcomes (8)

• Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator

  Up to approximately 46 months

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 46 months

• Quality of life during treatment

  Baseline (Cycle 1 Day 1: Predose) and up to approximately 46 months

• PFS Per RECIST 1.1 as Assessed by Investigator in All Participants

  Up to approximately 46 months

• OS in All Participants

  Up to approximately 46 months

Study Arms (1)

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.

Drug: Low-dose Pembrolizumab Plus Chemotherapy (Paclitaxel plus Carboplatin or Cisplatin)

Interventions

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).

Low-dose Pembrolizumab Plus Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ) 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.

You may not qualify if:

• ) 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.
• ) 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.

Sponsors & Collaborators

• Instituto Nacional de Cancer, Brazil: lead

Study Sites (1)

Instituto Nacional de Cancer

Rio de Janeiro, Rio de Janeiro, 20231050, Brazil

RECRUITING

Related Publications (8)

• 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.

  PMID: 33538338 BACKGROUND

• 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.

  PMID: 36633525 BACKGROUND

• 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.

  PMID: 30638582 BACKGROUND

• 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.

  PMID: 25732161 BACKGROUND

• 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.

  PMID: 34534429 BACKGROUND

• 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.

  PMID: 27092830 BACKGROUND

• 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.

  PMID: 30052728 BACKGROUND

• 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.

  PMID: 33634869 BACKGROUND

MeSH Terms

Conditions

Recurrence

Interventions

pembrolizumab; Drug Therapy; Paclitaxel; Carboplatin; Cisplatin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Andreia c Melo, PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andreia C Melo, PhD

CONTACT

552132072988; andreia.melo@inca.gov.br

Cecilia F da Silva, PhD

CONTACT

552132072988; cecilia.silva@inca.gov.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 27, 2024
• First Posted: November 1, 2024
• Study Start: February 20, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2028
• Last Updated: February 24, 2025

Record last verified: 2025-02

Locations

BR (1)