Response to Pembrolizumab in Metastatic Melanoma: Computed Tomography Texture Analysis as a Predictive Biomarker

• Sponsor: Canadian Cancer Trials Group (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02740920
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 9
• Locations: 5
• Arm: 1
• Actual Duration (Months): 40.6
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Studies have shown that the study drug, pembrolizumab, works by helping the immune system. In this way, pembrolizumab may help to slow the growth of melanoma or may cause cancer cells to die. Compared to standard treatments, pembrolizumab seems to lengthen the time patients lived overall and the time without their cancer getting worse.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Melanoma	Drug: Pembrolizumab; Procedure: CT Scan	Phase 2

Detailed Description

The main purpose of this study is to find out if a type of CT (computed topography) scan can help to know if pembrolizumab is working. This CT scan (called Texture Analysis) looks at the tumour in fine detail. The use of this type of CT scan has not been studied in patients with metastatic melanoma. Investigators want to see if this CT scan will show if some patients being treated with pembrolizumab respond better than others.

One of the other purposes is to compare the costs within this trial to costs of the standard of care.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of the Assessment of Response to Pembrolizumab in Metastatic Melanoma: CT Texture Analysis as a Predictive Biomarker
• Actual Study Start Date: May 12, 2016
• Actual Primary Completion Date: Mar 22, 2019
• Actual Study Completion Date: Sep 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab 200mg IV Day 1 every 3 weeks.	Drug: Pembrolizumab; Procedure: CT Scan

Outcome Measures

Primary Outcome Measures

1. Measurement of Tumor Texture by CT Scan [12 months]

   To assess whether tumour texture parameters from a CT scan can differentiate patients who do and who do not respond to treatment with pembrolizumab. Trial closed due to slow accrual, analysis was no done for the primary outcome because data were not collected.

Secondary Outcome Measures

1. Overall Response Rate Assessed by CT Scan [24 months]

   To determine the overall response rate (complete + partial response)/total number of patients. Response and progression will be evaluated in this study using the revised international criteria (1.1) proposed by the RECIST (Response Evaluation Criteria in Solid Tumours) committee as well as the modified iRECIST guidelines. Response were assessed by CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed melanoma that is recurrent/metastatic and not amenable to potentially curative surgery.

• Presence of clinically and/or radiologically documented disease based on RECIST 1.1. At least one site of disease must be unidimensionally measurable by contrast-enhanced

CT scan as follows:

CT scan (with slice thickness of ≤ 5 mm) ≥ 10 mm --> longest diameter Lymph nodes by CT scan ≥ 15 mm --> measured in short axis

• Age ≥ 18 years.

• ECOG Performance Status of 0 to 1.

• Previous Therapy

Surgery:

Previous surgery is permitted provided that it has been at least 21 days prior to patient registration and that wound healing has occurred.

Systemic Therapy:

Patients may not have received any prior systemic therapy for metastatic melanoma.

Radiation:

Palliative radiation is permitted provided > 7 days has elapsed between last dose and enrollment on the trial.

• Laboratory Requirements Absolute neutrophils ≥ 1.5 x 10^{9/L Platelets ≥ 100 x 10}9/L Hemoglobin ≥ 90 g/L or ≥ 5.6 mmol/L (without transfusion or EPO dependency) Serum creatinine or measured or calculated creatinine: ≤1.5 x ULN or ≥ 60 mL/min for subject with creatinine clearance levels > 1.5 x ULN Serum Total Bilirubin ≤ 1.5 x ULN or Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver mets) Albumin ≥ 25 g/L

• Women/men of childbearing potential must have agreed to use a highly effective contraceptive method.

• Women of childbearing potential will have a serum or urine pregnancy test within 7 days prior to registration to determine eligibility.

• Patient consent must be obtained according to local Institutional and/or University Human Experimental Committee requirements.

• Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre.

Exclusion Criteria:

• Patients who have received prior systemic treatment for metastatic melanoma.

• Patients with known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

• Patients with a known history of or known positive for Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA [qualitative] is detected). Patients with unknown history of Hepatitis B virus (HBV) or Hepatitis C virus (HCV) will require screening.

• Patients with previously treated brain metastases may participate provided they are stable with no evidence of enlargement following radiation treatment and no acute radiation toxicity OR no evidence of enlargement at least 4 weeks prior to the first dose of study drug if untreated and are off systemic steroids for at least two weeks.

• Patients who are pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 4 months after the last dose of trial treatment.

• Patients who previously had a severe hypersensitivity reaction to treatment with another mAb.

• Patients with an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. (Only patients on active treatment are ineligible).

• Patients with a history of a malignancy (other than the disease under treatment in the study) within 5 years prior to first study drug administration.

• Patients on any systemic corticosteroid therapy within one week before the planned date for first dose of treatment or on any other form of immunosuppressive medication.

• Patients with an allergy to iodinated contrast media used for CT.

• Patients with a known history of active TB (Bacillus Tuberculosis).

• Patients with evidence of interstitial lung disease;

• Patients with known history of, or any evidence of active, non-infectious pneumonitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kingston Health Sciences Centre	Kingston	Ontario	Canada	K7L 2V7
2	London Regional Cancer Program	London	Ontario	Canada	N6A 5W9
3	Ottawa Hospital Research Institute	Ottawa	Ontario	Canada	K1H 8L6
4	Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
5	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1

Sponsors and Collaborators

• Canadian Cancer Trials Group
• Merck Sharp & Dohme LLC

Investigators

• Study Chair: Teresa Petrella, Sunnybrook Health Sciences Centre, Toronto ON

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 10, 2017

More Information

Publications

None provided.

• Responsible Party: Canadian Cancer Trials Group
• ClinicalTrials.gov Identifier: NCT02740920
• Other Study ID Numbers: I225
• First Posted: Apr 15, 2016
• Last Update Posted: Apr 14, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Melanoma; Pembrolizumab

Study Results

Participant Flow

Arm/Group Title	Pembrolizumab
Arm/Group Description	200mg IV Day 1 every 3 weeks. Pembrolizumab CT Scan
Period Title: Overall Study
STARTED	9
COMPLETED	9
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Pembrolizumab
Arm/Group Description	200mg IV Day 1 every 3 weeks. Pembrolizumab CT Scan
Overall Participants	9
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	3 33.3%
Male	6 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	7 77.8%
Unknown or Not Reported	2 22.2%
Performance status (Count of Participants)
Grade 0	6 66.7%
Grade 1	3 33.3%

Outcome Measures

1. Primary Outcome

Title	Measurement of Tumor Texture by CT Scan
Description	To assess whether tumour texture parameters from a CT scan can differentiate patients who do and who do not respond to treatment with pembrolizumab. Trial closed due to slow accrual, analysis was no done for the primary outcome because data were not collected.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Trial closed due to slow accrual, analysis was no done for the primary outcome because data were not collected.

Arm/Group Title	Pembrolizumab
Arm/Group Description	200mg IV Day 1 every 3 weeks. Pembrolizumab CT Scan
Measure Participants	0

2. Secondary Outcome

Title	Overall Response Rate Assessed by CT Scan
Description	To determine the overall response rate (complete + partial response)/total number of patients. Response and progression will be evaluated in this study using the revised international criteria (1.1) proposed by the RECIST (Response Evaluation Criteria in Solid Tumours) committee as well as the modified iRECIST guidelines. Response were assessed by CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All patients who received the protocol treatment.

Arm/Group Title	Pembrolizumab
Arm/Group Description	200mg IV Day 1 every 3 weeks. Pembrolizumab CT Scan
Measure Participants	9
Number of Response	2 22.2%
Nomuber of non-response	7 77.8%

Adverse Events

Time Frame	24 months
Arm/Group Title	Pembrolizumab
Arm/Group Description	200mg IV Day 1 every 3 weeks. Pembrolizumab CT Scan
All Cause Mortality
	Pembrolizumab
	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)
Serious Adverse Events
	Pembrolizumab
	Affected / at Risk (%)	# Events
Total	2/9 (22.2%)
General disorders
Fever	1/9 (11.1%)
Musculoskeletal and connective tissue disorders
Muscle weakness right-sided	1/9 (11.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Other neoplasms benign, malignant and unspecified	1/9 (11.1%)
Nervous system disorders
Depressed level of consciousness	1/9 (11.1%)
Dysarthria	1/9 (11.1%)
Other nervous system disorders	1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Pembrolizumab
	Affected / at Risk (%)	# Events
Total	8/9 (88.9%)
Cardiac disorders
Chest pain - cardiac	1/9 (11.1%)
Eye disorders
Blurred vision	1/9 (11.1%)
Gastrointestinal disorders
Abdominal pain	1/9 (11.1%)
Constipation	1/9 (11.1%)
Diarrhea	1/9 (11.1%)
Other gastrointestinal disorders	2/9 (22.2%)
General disorders
Edema limbs	1/9 (11.1%)
Fatigue	4/9 (44.4%)
Fever	1/9 (11.1%)
Non-cardiac chest pain	2/9 (22.2%)
Pain	2/9 (22.2%)
Infections and infestations
Other infections and infestations	1/9 (11.1%)
Upper respiratory infection	3/9 (33.3%)
Musculoskeletal and connective tissue disorders
Muscle weakness right-sided	1/9 (11.1%)
Pain in extremity	2/9 (22.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Other neoplasms benign, malignant and unspecified	1/9 (11.1%)
Nervous system disorders
Depressed level of consciousness	1/9 (11.1%)
Dysarthria	1/9 (11.1%)
Headache	1/9 (11.1%)
Other nervous system disorders	1/9 (11.1%)
Peripheral sensory neuropathy	1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Cough	3/9 (33.3%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/9 (11.1%)
Other skin and subcutaneous tissue disorders	3/9 (33.3%)
Pruritus	1/9 (11.1%)
Rash acneiform	1/9 (11.1%)
Rash maculo-papular	3/9 (33.3%)
Vascular disorders
Hypertension	1/9 (11.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.