Axitinib +/- Pembrolizumab in First Line Treatment of mPRCC

NCT05096390 | Recruiting Phase 2

• 2 other identifiers: PAXIPEM (ET21-023)ET21-023
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 12

Brief Summary

Multicenter Phase II Study of Axitinib +/- Pembrolizumab in First Line Treatment for Patients With Locally Advanced or Metastatic Papillary Renal Cell Carcinoma (PRCC)

Conditions

Papillary Renal Cell Carcinoma Type 2

Keywords

PRCC

Outcome Measures

Primary Outcomes (1)

• Efficacy of axitinib + pembrolizumab versus axitinib in patients with locally advanced or metastatic type 2 papillary renal carcinoma in first-line treatment.

  6-month objective response rate (6m-ORR), defined as the proportion of patients with CR or PR at 6 months

  At 6 months for each patient

Secondary Outcomes (5)

• Duration of response (DOR)

  Week 4, 7, 9-10, 18-19, 27-28 then Months 8, 10, 12, 14, 16, 18, 20, 22, 24

• Best overall response (BOR) using RECIST 1.1

  Up to 24 months for each patient

• Progression-free survival (PFS)

  Up to 24 months for each patient

• Overall survival (OS)

  Up to 48 months

• Incidence of adverse events

  Up to 48 months

Study Arms (2)

axitinib + pembrolizumab

EXPERIMENTAL

Axitinib will be administrated orally 5 mg twice a day, with a dose adaptations to the manufacturer recommendations in both groups. Doses can be increased up to 10 mg twice daily. Pembrolizumab will be administrated intravenously (IV) over 30 minutes at the dose of 200 mg every 3 weeks according to recent summary of product characteristics (SPC) together with axitinib.

Drug: Axitinib Oral Tablet [Inlyta]; Drug: Pembrolizumab Injection [Keytruda]

axitinib alone (control)

ACTIVE COMPARATOR

Axitinib will be administrated orally 5 mg twice a day, with a dose adaptations to the manufacturer recommendations in both groups. Doses can be increased up to 10 mg twice daily.

Drug: Axitinib Oral Tablet [Inlyta]

Interventions

Axitinib Oral Tablet [Inlyta] DRUG

Axitinib 5 up to 10mg twice a day

axitinib + pembrolizumab; axitinib alone (control)

Pembrolizumab Injection [Keytruda] DRUG

Pembrolizumab intravenously over 30 min minutes at 200 mg every 3 weeks

axitinib + pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years on the day of signing informed consent.
• No prior systemic treatment for renal cancer (chemotherapy, immunotherapy, anti-angiogenic drugs, or treatment under evaluation) even in adjuvant setting.
• At least one measurable site of disease according to RECIST v1.1.
• In case of prior radiation therapy, discontinuation of irradiation for at least 3 weeks before first dose of study treatment, with at least 1 site kept/preserved for evaluation. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks - limited field (\<10% of the whole body)) to non-CNS disease.
• Hemoglobin ≥ 9.0 g/dl ou ≥ 5.6 mmol/l, neutrophils ≥ 1 000/mm3 (1.0 G/l), Platelets ≥ 100 000/mm3 (100 G/l),
• Serum creatinine ≤ 2 x ULN OR creatinine clearance ≥ 50 ml/min/1.73m2 (calculated using either MDRD or CKD-EPI formula),
• AST and ALT ≤ 2.5 x ULN (or ≤ 5 x ULN in case of liver metastasis),
• Total serum bilirubin ≤ 1.5 x ULN (or direct bilirubin ≤ ULN for participants with total bilirubin levels \>1.5 × ULN),
• Absence of significant proteinuria (\<0.5 g/24h) confirmed by urinary dipstick test. If the dipstick test is ≥ 2+, proteinuria will be quantitated on a complete 24h urine sample (\< 1 g/l of protein/24h sample)
• Covered by a medical/health insurance.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
• Patients of childbearing potential accepting to use effective contraception or abstain from heterosexual activity during study treatment and within 4 months after final dose of study therapy or being surgically sterile. Refer to Appendix 1 for approved methods of contraception.
• Signed and dated approved informed consent form before any study specific procedures or assessments.

You may not qualify if:

• Metastases with high risk of nervous compression or bone lesion with high risk of fracture.
• Prior history of other malignancies other than PRCC (except for curatively treated basal cell or squamous cell carcinoma of the skin or in situ uterine cervix carcinoma) unless the subjects has been free of the disease for at least 5 years.
• Significant cardiovascular disease, including:
• Disorder of left ventricular function with a left ventricular ejection fraction (LVEF) \< 50%,
• History of serious ventricular arrhythmia (ie ventricular tachycardia or ventricular fibrillation),
• Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication),
• Any anti-coagulation therapy except prophylactic low dose.
• History of auto-immune disease except thyroiditis more than 6 months ago.
• History of any allograft.
• HIV, HBV, HCV active infections.
• Any active acute or chronic or uncontrolled infection/disorder that would impair the ability to evaluate the patient or the ability for the patient to complete the study.
• Known history of active TB (Bacillus Tuberculosis).
• Interstitial lung disease, respiratory insuffisancy whatever the cause.
• Prior (non-infectious) pneumonitis requiring systemic corticosteroid therapy or current pneumonitis.
• Inability to swallow oral medications, or presence of active inflammatory bowel disease, partial or complete bowel obstruction or chronic diarrhea.

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (12)

Ico - Paul Papin

Angers, 49055, France

NOT YET RECRUITING

CHU de BESANCON

Besançon, 25030, France

NOT YET RECRUITING

Chu Bordeaux

Bordeaux, 33000, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63011, France

NOT YET RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

Institut Paoli-Calmettes

Marseille, 13009, France

RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

Ap-Hp Hôpital Europeen Georges Pompidou

Paris, 75004, France

NOT YET RECRUITING

Ico-Rene Gauducheau

Saint-Herblain, 44805, France

NOT YET RECRUITING

Iuct-Oncopole Institut Claudius Regaud

Toulouse, 31059, France

RECRUITING

Institut de Cancerologie de Lorraine - Alexis Vautrin

Vandœuvre-lès-Nancy, 54519, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

MeSH Terms

Interventions

Axitinib; pembrolizumab

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sylvie NEGRIER, PhD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sylvie NEGRIER

CONTACT

0478782751; sylvie.negrier@lyon.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, randomized, prospective, phase II study

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: October 27, 2021
• Study Start: June 1, 2022
• Primary Completion: October 1, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 25, 2024

Record last verified: 2024-01

Locations

FR (12)