Study of Propranolol Plus Sunitinib in First-line Treatment of Metastatic Renal Cell Carcinoma

NCT03323710 | Withdrawn Phase 2

• 1 other identifier: PS-001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to assess antineoplastic efficacy, safety, influence on quality of life and disease-related stress of propranolol taken in combination with sunitinib in previously untreated metastatic renal cell carcinoma

Conditions

Renal Cell Carcinoma

Keywords

Metastatic; Renal Cell Carcinoma; Kidney Cancer; Sunitinib; Sutent; Tyrosine Kinase Inhibitor; Angiogenesis Inhibitor; Propranolol; Beta-blocker; First-line

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective Response Rate (ORR) is defined as the percentage of patients who have achieved partial response (PR) or complete response (CR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.

  Up to 18 months

Secondary Outcomes (8)

• Overall Survival (OS)

  Up to 18 months

• Progression-free Survival (PFS)

  Up to 18 months

• Disease Control Rate (DCR)

  Up to 18 months

• Safety profile as assessed by Common Terminology Criteria for Adverse Events v4.03 summarized by type, frequency, and severity.

  Up to 18 months

• Health-related Quality of Life (QoL)

  Up to 18 months

Study Arms (1)

Propranolol plus Sunitinib

EXPERIMENTAL

Drug: Propranolol; Drug: Sunitinib

Interventions

Propranolol DRUG

Propranolol will be administered orally at a starting dose of 40 mg (one tablet) two times a day (total daily dose of 80 mg). In case of acceptable safety profile, the dose may be increased to 80 mg (two tablets) two times a day (total daily dose of 160 mg) or farther to 80 mg (two tablets) three times a day (total daily dose of 240 mg).

Propranolol plus Sunitinib

Sunitinib DRUG

Sunitinib will be administered orally at a starting dose of 50 mg once daily, for 4 consecutive weeks, followed by a 2-week rest period (schedule 4/2) to comprise a complete cycle of 6 weeks.The schedule may be changed to 2 weeks on / 1 week off (schedule 2/1) and a daily dose may be reduced to 37.5 mg or 25 mg to decrease the level of toxic side effects.

Also known as: Sutent

Propranolol plus Sunitinib

Eligibility Criteria

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

You may qualify if:

• Patients are eligible to be included in the study only if they meet all of the following criteria:
• Histological diagnosis of clear-cell renal cell carcinoma (RCC) or mixed-type RCC with more than 60% of clear-cell component.
• Diagnosis of stage IV RCC (primary metastatic or recurrence after surgical procedure).
• Prior nephrectomy (complete or partial).
• Presence of measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1.
• Karnofsky performance status score of 80-100%.
• Favourable- or intermediate-risk according to Memorial Sloan Kettering Cancer Center criteria.
• Adequate organ function, including the following:
• hepatic: total bilirubin ≤ 2 times the upper limit of normal (excluding patients with Gilbert syndrome), aspartate aminotransferase and alanine aminotransferase ≤ 5 times the upper limit of normal,
• renal: serum creatinine ≤ 2 times the upper limit of normal,
• bone marrow: absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100000/mm3, hemoglobin ≥ 9.5 g/dl.
• Normal thyroid function (natural or with supplementation of thyroid hormones) defined as thyroid-stimulating hormone within limits of normal.
• Age eighteen years or older on the day of consent.
• Written informed consent prior to study entry.

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• Prior systemic pharmacotherapy of RCC.
• Treatment with propranolol within 6 months of study entry.
• Metastases in central nervous system (patients who had central nervous system metastases that were surgically resected and/or treated with radiotherapy in the past and now are without neurological symptoms, are allowed on protocol).
• Female patients who are pregnant or breast feeding or adults of reproductive potential who are not using effective birth control methods.
• Presence of other malignancies (patients with carcinoma in situ of the cervix or basal cell carcinoma of the skin are allowed on protocol).
• Presence of any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• heart failure of New York Heart Association Class III or IV, significant cardiac arrhythmia or any other clinically significant cardiovascular disease,
• unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of entering the study,
• severely impaired respiration as defined as O2 saturation that is ≤ 90% at rest on room air,
• uncontrolled diabetes as defined by fasting serum glucose \> 1.5 times the upper limit of normal,
• ejection fraction less than 40% (measured at echocardiography),
• significant liver disease such as cirrhosis, active hepatitis or chronic persistent hepatitis,
• active (acute or chronic) infections requiring antimicrobial intervention.
• Concomitant treatment with:

Sponsors & Collaborators

• Military Institute od Medicine National Research Institute: lead

Study Sites (1)

Military Institute of Medicine

Warsaw, Masovian Voivodeship, 04141, Poland

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis; Kidney Neoplasms

Interventions

Propranolol; Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Paweł Chrom, M.D.

  Military Institute od Medicine National Research 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: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Model Details: Two-stage optimal Simon design

Study Record Dates

• First Submitted: October 22, 2017
• First Posted: October 27, 2017
• Study Start: September 1, 2018
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: January 9, 2019

Record last verified: 2019-01

Locations

PL (1)