Pembrolizumab With Axitinib in Recurrent Endometrial Cancer

NCT04197219 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: CASE4819
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main purpose of this study is to see if adding the experimental medication, axitinib, to usual treatment with pembrolizumab will work better than pembrolizumab alone. The study team will look at overall safety and side effects of the combination of axitinib and pembrolizumab to see how well it is tolerated. Researchers will also want to take some research blood samples to explore what effects the combination of treatment has on participants' cells and immune system and to see if there are things in participants' blood that can predict a response or resistance to the combined treatment.

Conditions

Recurrent Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) at 12 weeks by RECIST 1.1

  Percent of participants with ORR, defined as those having either a partial or complete response (according to RECIST 1.1) per investigator determination at 12 weeks from the date of study enrollment. Complete response (CR): Disappearance of all target lesions Partial response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD

  Up to 12 weeks from start of treatment

Secondary Outcomes (4)

• Average overall Survival (OS)

  Assessed up to 60 months

• Clinical benefit rate

  Up to 12 weeks from start of treatment

• Number of participants with grade 3 and 4 immune and non-immune related toxicities assessed via NCI CTCAE v.5.03

  90 days from end of treatment

• Average progression-free survival (PFS)

  12 months from end of treatment

Other Outcomes (1)

• Translational endpoints

  12 months from end of treatment

Study Arms (1)

Pembrolizumab & axitinib

EXPERIMENTAL

All participants enrolled will receive pembrolizumab as standard of care (SOC) combined with axitinib. Axitinib will be self-administered orally twice daily at 5 mg. On days when both drugs are administered, axitinib will be administered first, followed by pembrolizumab. Treatment will continue until disease progression or unacceptable grade 3/4 toxicities. For patients with a complete response to therapy, maintenance therapy with both drugs will be continued for 12 months.

Drug: Pembrolizumab; Drug: Axitinib

Interventions

Pembrolizumab DRUG

200 mg IV day 1 of each cycle every 21 days

Pembrolizumab & axitinib

Axitinib DRUG

5 mg PO BID continuously

Pembrolizumab & axitinib

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have recurrent endometrial cancer with deficient mismatch repair system. Mismatch repair deficiency is defined by 1. Immunohistochemistry with loss of expression of one of these proteins in tumor tissue as defined by standard of care: MLH1, MSH2, MSH6 and PMS2, 2. Microstaellite (MSI) unstable by PCR per standard of care, 3. MSI high by next generation sequencing using commercial platform specifically CARIS, TEMPUS or Foundation testing.
• Subjects must have histologically confirmed endometrioid, clear cell, high grade serous, undifferentiated carcinoma or mixed histology.
• Must have had prior therapy with a PD1 inhibitor, pembrolizumab.
• Up to 5 prior lines of therapy are allowed.
• Prior anti-angiogenesis therapy is not allowed. Bevacizumab if given with chemotherapy in primary or adjuvant setting is allowed if treatment-free interval exceeded 6 months.
• Subjects must have measurable disease based on RECIST 1.1 with at least one target lesion.
• Subjects must have an ECOG performance status of 0-1.
• Subjects must have normal organ and marrow function as defined below within 14 days of enrollment unless otherwise indicated:
• Hemoglobin ≥ 9.0 g/dl (may have been transfused)
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) range
• AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN orAST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
• Estimated Creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
• TSH within normal institutional limits. If elevated, patient can be eligible if evaluated by an endocrine specialist, placed on replacement therapy and deemed eligible with no current or prior autoimmune disease.

You may not qualify if:

• Patients with sarcoma or carcinosarcoma
• Mismatch repair proficient tumors
• Patients with primary platinum refractory cancer defined as progressing during or within 3 months of completing primary platinum therapy.
• Prior anti-cancer therapy within 3 weeks prior to study enrollment.
• Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable.
• Patients having received prior therapy with PD1 or PDL1 or CTLA4 inhibitors or other immunotherapeutic agents except pembrolizumab.
• Patients having received prior anti-VEGF therapy as explained above
• Bowel obstruction (with or without gastrostomy tube) or inability to take oral medications
• Patients with a prior or current bowel perforation or fistula
• Uncontrolled hypertension defined as 140/90 or greater despite medical management with multiple medications
• ECOG performance \>1
• Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• Patients currently on immunosuppressive therapy except:
• Intra-nasal, inhaled, topical or local steroid injections (e.g., intra-articular injection)
• Steroids as premedication for hypersensitivity reaction (e.g., CT scan premedication)."

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

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MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

pembrolizumab; Axitinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

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

• Haider Mahdi, MD

  Cleveland Clinic Women's Health 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

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: December 13, 2019
• Study Start: February 1, 2021
• Primary Completion: January 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 5, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share