A Study to Evaluate Apatinib (Also Known as Rivoceranib) Plus Nivolumab in Participants With Unresectable or Metastatic Cancer

NCT03396211 | Completed Phase 1 FDA Drug

• 1 other identifier: LSK-AM107
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-labeled, single-center, Phase I study to evaluate the safety, tolerability, and efficacy of apatinib with nivolumab treatment in participants with unresectable or metastatic cancer. Total study duration will be approximately 50 months: 12 months of recruitment plus 6 months of treatment and subsequent survival follow up.

Conditions

Cancer

Keywords

Metastatic; Unresectable

Outcome Measures

Primary Outcomes (7)

• Number of Participants with Treatment Emergent Adverse Events (TEAEs)

  Up to approximately 5 years

• Objective Response Rate (ORR): Percentage of Participants who Achieve Confirmed Complete Response (CR) or Partial Response (PR)

  ORR per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and/or iRECIST criteria.

  Up to approximately 5 years

• Best Overall Response Rate (BOR)

  BOR is the best response, according to RECIST v1.1 and/or RECIST criteria, recorded over the duration of the study until disease progression, or recurrence.

  Up to approximately 5 years

• Time To Response (TTR)

  TTR is the time lapsed from enrollment until documented response according to RECIST v1.1 and/or iRECIST criteria.

  Up to approximately 5 years

• Duration of Response (DoR)

  DoR is the time from documented tumor response (PR or CR) until disease progression or death from any cause, whichever occurs first.

  Up to approximately 5 years

• Disease Control Rate (DCR)

  DCR is the proportion of participants with radiologically documented stable or decreased tumor burden per RECIST v1.1 and/or iRECIST criteria.

  Up to approximately 5 years

• Duration of Disease Control (DDC)

  DDC is the time from enrollment until disease progression or death from any cause, whichever occurs first. Disease progression will be evaluated by RECIST v1.1 and/or iRECIST criteria.

  Up to approximately 5 years

Secondary Outcomes (3)

• Overall Survival (OS)

  Up to approximately 5 years

• Event Free Survival (EFS)

  Up to approximately 5 years

• Progression Free Survival (PFS)

  Up to approximately 5 years

Study Arms (1)

Apatinib with Nivolumab

EXPERIMENTAL

Participants will receive an oral dose of apatinib once per day with a fixed dose of nivolumab given intravenously every 2 weeks.

Drug: Apatinib; Drug: Nivolumab

Interventions

Apatinib DRUG

Apatinib tablets

Also known as: Rivoceranib, Apatinib Mesylate

Apatinib with Nivolumab

Nivolumab DRUG

Fixed dose of nivolumab given intravenously every 2 weeks

Also known as: Opdivo

Apatinib with Nivolumab

Eligibility Criteria

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

You may qualify if:

• Documented primary diagnosis of histologic- or cytologic-confirmed solid tumor cancer inclusive of gastric adenocarcinoma, renal cell carcinoma, melanoma, non-small cell lung cancer (NSCLC), breast cancer, angiosarcoma, leiomyosarcoma, synovial sarcoma, and alveolar soft part sarcoma or other solid tumor for which anti-Vascular endothelial growth factor receptor (VEGFR)2 targeted therapy could be applicable.
• Locally advanced unresectable or metastatic disease.
• Nivolumab treatment naive and able to begin nivolumab treatment concurrently with initiation of apatinib or have received at least 3 doses of nivolumab treatment and are continuing nivolumab therapy.
• or more measurable lesions per RECIST v1.1.
• Participants who have adequate bone-marrow, renal and liver function including:
• Renal: serum creatinine \< 1.5× upper limit of normal (ULN); urinary protein should be\< 2+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥ 2+, then a 24-hour urine or urine protein/creatinine ratio must be collected and must demonstrate \<2 g of protein in 24 hours to allow participation in the study.
• Hepatic: serum bilirubin \< 1.5× ULN, aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0× ULN(≤ 4.0× ULN, if with liver metastases).
• Blood coagulation tests: Partial thromboplastin time (PTT) and international normalized ratio (INR) ≤ 1.5× ULN and ≤ 1.5×ULN, respectively.
• Eastern Cooperative Oncology Group (ECOG) performance status are evaluated to be ≤ 1 (Participants with ECOG performance status of 2 may be enrolled only with advance review and written approval by the medical monitor).
• Expected survival of ≥ 12 weeks, in the judgement of the investigator.
• Ability to swallow the study drug tablets.

You may not qualify if:

• History of another malignancy within 2 years prior to enrollment, unless it does not pose a significant risk to life expectancy as per the investigator.
• Central nervous system (CNS) metastases as shown by radiology records or clinical evidence of symptomatic CNS involvement in the last 3 months prior to enrollment. Participants are eligible if metastases have been treated and have returned to neurologic baseline or are neurologically stable (except for residual signs or symptoms related to the CNS treatment).
• Cytotoxic chemotherapy, surgery, radiotherapy or other targeted therapies and checkpoint inhibitors (excluding nivolumab if not nivolumab treatment naive) within 3 weeks (4 weeks in cases of ramucirumab, mitomycin C, nitrosourea, lomustine; 1 week in case of biopsy) prior to enrollment (adjuvant radiotherapy given to local area for non-curative symptom relief is allowed until 2 weeks before enrollment).
• Any other therapies including biological and approved therapies within 3 half-lives or 3 weeks whichever is longer and have not recovered from all toxicities from the treatment.
• Therapy with clinically significant systemic anticoagulant or anti thrombotic agents within 7 days prior to enrollment that may prevent blood clotting and, in the investigator's opinion, could place the participants at risk. Maximum dose of 325 milligram (mg)/day of aspirin is allowed.
• History of bleeding diathesis or clinically significant bleeding within 14 days prior to enrollment.
• History of clinically significant thrombosis (bleeding or clotting disorder) within the past 3 months prior to enrollment that, in the investigator's opinion, may place the participant at risk of side effects from anti-angiogenesis products.
• History of gastrointestinal bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3 months prior to enrollment that, in the investigator's opinion, may place the participant at risk of side effects from anti-angiogenesis products.
• Myocardial infarction or an unstable angina pectoris within 3 months prior to enrollment.
• Prior major surgery or fracture within 3 weeks prior to enrollment or presence of any non-healing wound (procedures such as catheter placement are not considered to be major).
• Participation in any other interventional clinical trial, within 4 weeks prior to enrollment or while participating in this study.
• Previous treatment with apatinib.
• Hypersensitivity to apatinib or components of its formulation.
• History of uncontrolled hypertension (\[HTN\], blood pressure ≥ 140/90 millimeters of mercury \[mmHg\]) and change in anti hypertensive medication within 7 days prior to enrollment) that is not well managed by medication and the risk of which may be precipitated by VEGF inhibitor therapy.
• History of severe adverse events including uncontrolled HTN or other common anti-angiogenesis class drug effects that were related to ramucirumab or bevacizumab discontinuation and/or may indicate a higher risk to the safety of the participant if provided further anti-angiogenesis treatment, in the investigator's opinion.

Sponsors & Collaborators

• Elevar Therapeutics: lead

Study Sites (1)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Interventions

apatinib; Nivolumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2017
• First Posted: January 10, 2018
• Study Start: December 22, 2017
• Primary Completion: October 28, 2020
• Study Completion: March 16, 2022
• Last Updated: April 7, 2023

Record last verified: 2023-04

Locations

US (1)