Safety and clinical activity of avelumab with Axitinib in patients with advanced or metastatic previously treated non small cell lung cancer or urothelial cancer not previously treated who are unable to receive cisplatin.
- Conditions
- Advanced or Metastatic previously treated non-small cell lung cancer or treatment naïve cisplatin-ineligible urothelial cancer.MedDRA version: 20.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-004345-24-ES
- Lead Sponsor
- Pfizer Inc. 235 East 42nd Street, New York,NY 10017
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 80
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Diagnosis:
a. NSCLC Cohort: Histologically or cytologically confirmed diagnosis of NSCLC that is locally advanced or metastatic:
-No activating EGFR mutations, Anaplastic lymphoma kinase (ALK) translocations/rearrangements, or c-ros oncogene 1 (ROS1) translocations/rearrangements where testing is standard of care.
-Have received at least 1 prior platinum-based chemotherapy regimen for locally advanced or metastatic NSCLC.
-No more than 2 prior lines of systemic therapy for locally advanced or metastatic disease.
-If disease progression occurred during or within 6 months after neoadjuvant/adjuvant chemotherapy or radiotherapy ?chemotherapy, the regimen is counted as 1 prior treatment regimen towards the allowed limit of prior treatment ??regimens.
-Checkpoint inhibitor naïve.
b. UC Cohort: Histologically or cytologically confirmed diagnosis of transitional cell carcinoma (TCC) of the urothelium (if mixed, more than 50% TCC component) including bladder, urethra, ureters, or renal pelvis that is locally
advanced or metastatic:
-No prior systemic treatment for locally advanced or metastatic disease. Prior neoadjuvant or adjuvant therapy is ???permitted if disease progression occurred >12 months after the completion of therapy.
-Checkpoint inhibitor naïve.
-Ineligible for receiving cisplatin-containing front-line chemotherapy based at least one of the following criteria:
i. ECOG performance status (PS) 2;
ii. Renal dysfunction (defined as creatinine-clearance <60 ml/min);
iii. Grade 2 peripheral neuropathy;
iv. Grade 2 hearing loss (hearing loss measured by audiometry of 25 decibels at two contiguous frequencies)
2. Measurable disease by RECIST v1.1 with at least 1 measurable lesion that has not previously been irradiated.
3. Availability of an archival formalin-fixed and paraffin-embedded (FFPE) tumor tissue block from primary diagnosis specimen or metastatic specimen (if available). If a FFPE tissue block cannot be provided, then 15 unstained slides (10 minimum) will be acceptable. If such an archived sample is not available, a de novo (ie, fresh) tumor sample must be obtained prior to study enrolment.
4. ECOG PS: 0 or 1. For UC patients, ECOG PS 2 is permitted as part of cisplatin-ineligibility criteria.
5. Age 18 years.
6. Estimated life expectancy of at least 90 days.
7. Adequate hepatic function defined by:
a. Total serum bilirubin 1.5 × the upper limit of normal range (ULN);
b. AST and ALT 2.5 × ULN; for subjects with documented metastatic disease to the liver, AST and ALT levels 5 × ULN.
8. Adequate bone marrow function including:
a. Absolute Neutrophil Count (ANC) 1,500/mm3 or 1.5 x 109 /L;
b. Platelets 100,000/mm3 or 100 x 109 /L;
c. Hemoglobin 9 g/dL (5.6 mmol/L) (may have been transfused).
9. Adequate renal function defined by:
a. Estimated creatinine clearance 30 mL/min as calculated using the Cockcroft-Gault (CG) equation.
b. Urinary protein <2+ by urine dipstick. If dipstick is 2+, then 24-hour urinary protein <2 g per 24 hours.
10. Left ventricular ejection fraction (LVEF) lower limit of normal (LLN) as assessed by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO).
11. No evidence of uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be 140 mm Hg, and the baseline d
Patients with any of the following characteristics/conditions will not be included in the study:
1. Prior immunotherapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti- CD137, anti-OX-40, anti-glucocorticoid induced tumor necrosis factor (TNF) receptor (GITR), anti-lymphocyte activation gene-3 (LAG-3), anti- T cell immunoglobulin and mucin (TIM-3) domain, or anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody (including
ipilimumab).
2. Prior treatment with an anti-VEGF pathway TKI; prior use of anti-VEGF pathway mAb is permitted.
3. Patients with newly diagnosed brain metastases or 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 enrollment, have discontinued corticosteroid treatment for these metastases for at least 14 days prior to study enrollment, and are neurologically stable.
4. Diagnosis of any other malignancy within 5 years prior to study enrollment. Adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the bladder, breast, or cervix, or low grade (Gleason ?6) prostate cancer on surveillance without any plans for treatment intervention (eg, surgery, radiation, or castration) are
allowed.
5. Radiologically documented evidence of major blood vessel invasion or encasement by cancer (ie, invasion into the fat plane between the vessel wall and tumor) or intratumor cavitation, regardless of tumor histology.
6. Current use of immunosuppressive medication at the time of study enrollment, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (eg, intra-articular injection); b. Systemic corticosteroids at physiologic doses 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity
reactions.
7. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo-or hyperthyroid disease not requiring immunosuppressive treatment are
eligible.
8. Prior organ transplantation including allogenic stem-cell transplantation.
9. Active infection requiring systemic therapy.
10. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
11. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
12. Administration of a live vaccine within 28 days prior to study enrollment.
13. Known prior severe hypersensitivity to the investigational products or any component in their formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03
Grade 3).
14. Persisting toxicity related to prior therapy (NCI CTCAE v4.03 Grade >1); however, alopecia, sensory neuropathy Grade 2, or other Grade 2 AEs not constituting a safety risk based on Investigator's judgment are
acceptable. For UC patients, Grade 2 peripheral neuropathy is permitted as part of cisplatin-ineligibility criteria.
15. NCI CTCAE Grade 3 hemorrhage within 28 days prior to study enrollment.
16. Hemoptysis (1/2 teaspoon of bright red blood episode with cough) within 28 days prior to enrolment.
17. Evidence of inadequate wound healing.
18. History of abdominal fistula, gastrointestinal per
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method