Avelumab, Palbociclib and Axitinib in Advanced RCC

NCT05176288 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 21-575
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this study is to see whether the combination of 3 drugs (axitinib, avelumab and palbociclib) is safe and effective in slowing down the growth of advanced clear cell renal cell carcinoma (ccRCC) in patients that have not received any prior systemic treatment. The names of the study drug involved in this study are/is:

• Axitinib
• Avelumab
• Palbociclib

Conditions

Advanced Clear Cell Renal Cell Carcinoma

Keywords

Advanced Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (ORR)

  Objective response rate (ORR) is defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taken as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, for duration of therapy assessed up to 100 months

Secondary Outcomes (2)

• Median Progression-free survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Median Overall Survival (OS)

  Participants followed for long-term for survival every 6 months from the end of treatment until death or lost to follow-up, up to 2 years after treatment discontinuation.

Study Arms (1)

Axitinib, Avelumab and Palbociclib

EXPERIMENTAL

During each 28 day (+/- 3 days) study cycle, all participants will receive: * Axitinib: 2x Daily until it is determined participant must stop the drug * Palbociclib: Taken 1x time per day on days 8-28 of each cycle until it is determined participant must stop the drug. * Avelumab: Once every 2 weeks continued for up to 2 years or earlier if it is determined participant must stop the study drug

Drug: Axitinib; Drug: Palbociclib; Drug: Avelumab

Interventions

Axitinib DRUG

Taken Orally

Also known as: Inlyta

Axitinib, Avelumab and Palbociclib

Palbociclib DRUG

Taken Orally

Also known as: Ibrance

Axitinib, Avelumab and Palbociclib

Avelumab DRUG

Intravenous infusion

Also known as: Bavencio

Axitinib, Avelumab and Palbociclib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed unresectable advanced or metastatic renal cell carcinoma with a clear cell component. Patient with sarcomatoid histology are accepted.
• A formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from a de novo tumor biopsy obtained during screening will be required (biopsied tumor lesion should not be a RECIST target lesion). Alternatively, a recently obtained archival FFPE tumor tissue block (not cut slides from a primary or metastatic tumor resection or biopsy) can be provided if the following criteria are met:
• The biopsy or resection was performed within 1 year of registration AND
• The patient has not received any intervening systemic anti-cancer treatment from the time the tissue was obtained and registration onto the current study. If an FFPE tissue block cannot be provided as per documented regulations then 15 unstained slides (10 minimum) will be acceptable
• Availability of an archival FFPE tumor tissue block from primary diagnosis specimen (if available and not provided per above). If an FFPE tissue block cannot be provided as per documented regulations, then 15 unstained slides (10 minimum) will be acceptable
• Additional tumor biopsies for research purposes prior to starting therapy, after 2 months of therapy and at end of treatment are optional.
• Measurable disease as per RECIST 1.1. See section 11 for the evaluation of measurable disease.
• Age ≥ 18 years.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• Normal organ and marrow function as defined below:
• Absolute neutrophil count ≥1.5×109/L
• Platelets ≥100×109/L
• Hemoglobin ≥9g/dL (transfusions allowed)
• Total bilirubin ≤2 × institutional upper limit of normal (ULN) with the following exception: patients with known Gilbert disease should have a serum bilirubin ≤ 3 x ULN
• AST(SGOT)/ALT(SGPT) ≤3 × ULN with the following exception: patients with known liver metastases should have AST and ALT ≤ 5 × ULN

You may not qualify if:

• Treatment with the following prior therapies:
• Prior systemic therapy for advanced or metastatic RCC.
• Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has occurred within 12 months of last dose of such therapy. Treatment with an immune checkpoint inhibitor in the adjuvant setting is allowed providing more than 12 months have elapsed since completion of therapy.
• Prior treatment with any immunotherapeutic agent (IL-2, IFN-∝, anti-PD(L)-1, anti-CTLA-4, or any other antibody or drug targeting T-cell co-stimulation or immune checkpoint pathways).
• Prior therapy with axitinib or other therapies targeting VEGF pathway in the metastatic setting (adjuvant therapy is allowed.
• Prior therapy with any CDK4/6 inhibitor.
• Participants with untreated brain metastases. Participants with metastatic CNS tumors may participate in this trial, if the participant is ≥ 4 weeks from therapy completion (incl. radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy \>10 mg/day prednisone or equivalent. A repeat MRI or CT brain to show stability is required.
• Participants who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy to at least grade 1.
• Untreated deep vein thrombosis or pulmonary embolism, or event of deep vein thrombosis or pulmonary embolism within 2 weeks of treatment start. Patient should be on at least 1 week of anticoagulation before C1D1.
• Major surgery within the past 4 weeks or major radiation therapy within 2 weeks prior to treatment start. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed at least 48 hours prior to patient randomization.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease - also see 3.2.22, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• Persisting toxicity related to prior therapy NCI CTCAE v5.0 Grade \>1; however, sensory neuropathy Grade ≤2 is acceptable.
• Current or prior use of immunosuppressive medication within 7 days prior to randomization, except the following:
• Intranasal, inhaled, topical steroids, or local steroid injections (eg. intra-articular injection).
• Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent.

Sponsors & Collaborators

• Bradley A. McGregor, MD: lead
• Pfizer: collaborator

MeSH Terms

Interventions

Axitinib; palbociclib; avelumab

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

• Bradley McGregor, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 6, 2021
• First Posted: January 4, 2022
• Study Start: May 31, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2027
• Last Updated: September 7, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu