NCT03502746

Phase II Nivolumab and Ramucirumab for Patients With Previously-Treated Mesothelioma

Terminated Phase 2 Results posted Last updated 14 May 2024

What this trial tests

Phase 2 trial testing Nivolumab in Mesothelioma, Malignant in 34 participants. Terminated before completion.

Timeline

26 June 2018

Primary endpoint
11 May 2022

9 November 2023

Quick facts

Lead sponsor	Arkadiusz Z. Dudek, MD
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	34
Start date	26 June 2018
Primary completion	11 May 2022
Estimated completion	9 November 2023
Sites	4 locations across United States

Drugs / interventions tested

• Nivolumab (nivolumab) — full drug profile →
• Ramucirumab (RAMUCIRUMAB) — full drug profile →

Conditions studied

• Mesothelioma, Malignant — all drugs for Mesothelioma, Malignant →

Sponsor

Arkadiusz Z. Dudek, MD

Who can join

18 and older, any sex, with Mesothelioma, Malignant. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Response Rate Primary · Up to a maximum of 23 months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Response rate will be defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1.

Group	Value	95% CI
Nivolumab + Ramucirumab	22.6	9.6 – 41.1

Adverse Event Assessment Secondary · AE had been recorded from time of consent until 100 days after discontinuation of study drug or until a new anti-cancer treatment starts, whichever occurs first; up to a maximum of 28 months.

The frequency and severity of all grade ≥ 2 treatment related adverse events are reported by CTCAE v4 term.

Dyspnea

Group	Value	95% CI
Nivolumab + Ramucirumab	5

Hypertension

Group	Value	95% CI
Nivolumab + Ramucirumab	3

Proteinuria

Group	Value	95% CI
Nivolumab + Ramucirumab	9

Arial fibrillation

Group	Value	95% CI
Nivolumab + Ramucirumab	2

Abdominal Pain

Group	Value	95% CI
Nivolumab + Ramucirumab	1

Anorexia

Group	Value	95% CI
Nivolumab + Ramucirumab	2

Dehydration

Group	Value	95% CI
Nivolumab + Ramucirumab	1

Diarrhea

Group	Value	95% CI
Nivolumab + Ramucirumab	1

Progression-free Survival (PFS) Secondary · Time of treatment start until the criteria for disease progression or death, up to a maximum of 23 months.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from treatment start until disease progression met by RECIST 1.1 or death from any cause.

Group	Value	95% CI
Nivolumab + Ramucirumab	4.2	1.9 – 6.4

Overall Survival Secondary · Time of treatment start until death or date of last contact, up to a maximum of 32 months.

Overall survival (OS) is defined as time of treatment start until death or date of last contact.

Group	Value	95% CI
Nivolumab + Ramucirumab	12.5	6.3 – 23.5

Adverse events — posted to ClinicalTrials.gov

Time frame: All-Cause Mortality was monitored up to a maximum of 32 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 28 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nivolumab + Ramucirumab

Serious: 9/34 (26%)

Deaths: 22/34

Serious adverse events (9 terms)

Reaction	System	Nivolumab + Ramucirumab
ATRIAL FIBRILLATION	Cardiac disorders	—
DEHYDRATION	Metabolism and nutrition disorders	—
DIARRHEA	Gastrointestinal disorders	—
DYSPNEA	Respiratory, thoracic and mediastinal disorders	—
ESOPHAGEAL OBSTRUCTION	Gastrointestinal disorders	—
HEART FAILURE	Cardiac disorders	—
LOWER GASTROINTESTINAL HEMORRHAGE	Gastrointestinal disorders	—
MUSCLE WEAKNESS LOWER LIMB	Musculoskeletal and connective tissue disorders	—
PANCREATITIS	Gastrointestinal disorders	—

Other adverse events (97 terms — click to expand)

Reaction	System	Nivolumab + Ramucirumab
FATIGUE	General disorders	—
COUGH	Respiratory, thoracic and mediastinal disorders	—
ANOREXIA	Metabolism and nutrition disorders	—
PAIN	General disorders	—
PROTEINURIA	Renal and urinary disorders	—
DYSPNEA	Respiratory, thoracic and mediastinal disorders	—
EDEMA LIMBS	General disorders	—
GENERALIZED MUSCLE WEAKNESS	Musculoskeletal and connective tissue disorders	—
HEADACHE	Nervous system disorders	—
NAUSEA	Gastrointestinal disorders	—
ARTHRALGIA	Musculoskeletal and connective tissue disorders	—
DIARRHEA	Gastrointestinal disorders	—
RASH MACULO-PAPULAR	Skin and subcutaneous tissue disorders	—
STOMACH PAIN	Gastrointestinal disorders	—
WEIGHT LOSS	Investigations	—
BACK PAIN	Musculoskeletal and connective tissue disorders	—
CHEST WALL PAIN	Musculoskeletal and connective tissue disorders	—
DIZZINESS	Nervous system disorders	—
DRY SKIN	Skin and subcutaneous tissue disorders	—
HYPOTHYROIDISM	Endocrine disorders	—
NASAL CONGESTION	Respiratory, thoracic and mediastinal disorders	—
NON-CARDIAC CHEST PAIN	General disorders	—
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY	Skin and subcutaneous tissue disorders	—
ARTHRITIS	Musculoskeletal and connective tissue disorders	—
CONSTIPATION	Gastrointestinal disorders	—
CREATININE INCREASED	Investigations	—
DEPRESSION	Psychiatric disorders	—
FALL	Injury, poisoning and procedural complications	—
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY	General disorders	—
HYPERTENSION	Vascular disorders	—
HYPOMAGNESEMIA	Metabolism and nutrition disorders	—
INFUSION RELATED REACTION	General disorders	—
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	—
VOMITING	Gastrointestinal disorders	—
ABDOMINAL DISTENSION	Gastrointestinal disorders	—
ANXIETY	Psychiatric disorders	—
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	—
CHILLS	General disorders	—
DYSGEUSIA	Nervous system disorders	—
HEMATURIA	Renal and urinary disorders	—

Most-reported serious reactions: ATRIAL FIBRILLATION, DEHYDRATION, DIARRHEA, DYSPNEA, ESOPHAGEAL OBSTRUCTION, HEART FAILURE, LOWER GASTROINTESTINAL HEMORRHAGE, MUSCLE WEAKNESS LOWER LIMB.

Data from ClinicalTrials.gov NCT03502746 adverse events section.

Sponsor's own description

This study will evaluate the combination of Nivolumab and Ramucirumab in patients with previously-treated mesothelioma.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment.
   Yi M, Jiao D, Qin S, Chu Q, et al · · 2019 · cited 487× · PMID 30925919 · DOI 10.1186/s12943-019-0974-6
2. The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment.
   Kim SK, Cho SW. · · 2022 · cited 300× · PMID 35685630 · DOI 10.3389/fphar.2022.868695
3. Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment.
   Song Y, Fu Y, Xie Q, Zhu B, et al · · 2020 · cited 198× · PMID 32983126 · DOI 10.3389/fimmu.2020.01956
4. Emerging Treatments for Malignant Pleural Mesothelioma: Where Are We Heading?
   Cantini L, Hassan R, Sterman DH, Sterman DH, et al · · 2020 · cited 47× · PMID 32226777 · DOI 10.3389/fonc.2020.00343
5. Adverse Events of Concurrent Immune Checkpoint Inhibitors and Antiangiogenic Agents: A Systematic Review.
   Gao L, Yang X, Yi C, Zhu H. · · 2019 · cited 42× · PMID 31680957 · DOI 10.3389/fphar.2019.01173
6. Manipulation of the crosstalk between tumor angiogenesis and immunosuppression in the tumor microenvironment: Insight into the combination therapy of anti-angiogenesis and immune checkpoint blockade.
   Zheng W, Qian C, Tang Y, Yang C, et al · · 2022 · cited 30× · PMID 36439137 · DOI 10.3389/fimmu.2022.1035323
7. Tumor Vessel Normalization: A Window to Enhancing Cancer Immunotherapy.
   Li S, Zhang Q, Hong Y. · · 2020 · cited 28× · PMID 33287656 · DOI 10.1177/1533033820980116
8. New insights into the important roles of tumor cell-intrinsic PD-1.
   Zheng H, Ning Y, Zhan Y, Liu S, et al · · 2021 · cited 25× · PMID 34326692 · DOI 10.7150/ijbs.60114