Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR) (CAPTUR)

• ClinicalTrials.gov Identifier: NCT03297606
• Recruitment Status: Recruiting
• First Posted: September 29, 2017
• Last Update Posted: June 2, 2023
• Sponsor: Canadian Cancer Trials Group
• Collaborators: AstraZeneca; Bristol-Myers Squibb; Hoffmann-La Roche; Pfizer; Seagen Inc.
• Information provided by (Responsible Party): Canadian Cancer Trials Group

Study Description

Brief Summary:

Cancer drugs which target the effects of abnormal gene changes are called 'targeted therapies'. This study, called PM.1 or CAPTUR, will include some targeted therapies that are currently available. The purpose of this study is to find out what are the effects on a patient and their cancer when they are given a targeted therapy drug that is specific to an abnormal gene change in their cancer.

Condition or disease	Intervention/treatment	Phase
Lymphoma, Non-Hodgkin; Multiple Myeloma; Advanced Solid Tumors	Drug: Olaparib; Drug: Dasatinib; Drug: Nivolumab plus Ipilimumab; Drug: Axitinib; Drug: Bosutinib; Drug: Crizotinib; Drug: Palbociclib; Drug: Sunitinib; Drug: Temsirolimus; Drug: Erlotinib; Drug: Trastuzumab plus Pertuzumab; Drug: Vemurafenib plus Cobimetinib; Drug: Vismodegib; Drug: Tucatinib	Phase 2

Detailed Description:

Recent advances in laboratory technology have enabled the identification of changes in the genetic makeup of tumors that might be responsible for their malignant behavior such as uncontrolled growth and spread. Some of these changes can be 'druggable', i.e. there may be cancer medicines that can specifically act on the tumour's genetic abnormality. Several cancer centers and programs have initiated this type of molecular profiling across Canada, with the goal to identify 'druggable' changes in tumors to find matching therapy for patients. These include initiatives in British Columbia, Ontario and Quebec. The CAnadian Profiling and Targeted agent Utilization tRial (CAPTUR) will test the activity of a list of commercially available targeted agents in patients who have undergone tumor profiling and have 'druggable' changes identified in their cancers.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 720 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR): A Phase II Basket Trial
• Actual Study Start Date: October 6, 2017
• Estimated Primary Completion Date: January 31, 2026
• Estimated Study Completion Date: January 31, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1 - Arm CLOSED, no patients recruited; VEGFR1, VEGFR2, VEGFR3	Drug: Axitinib; 5mg orally twice daily
Experimental: Group 2 - Arm CLOSED, no patients recruited; BCR-ABL, SRC	Drug: Bosutinib; 500mg orally once daily
Experimental: Group 3 - Arm CLOSED; ALK, ROS1, MET	Drug: Crizotinib; 250mg orally twice daily
Experimental: Group 4 - Arm CLOSED, no patients recruited; KIT, PDGFRA, PDGFRB, ABL1	Drug: Dasatinib; 100mg administered orally once daily
Experimental: Group 5; EGFR	Drug: Erlotinib; 150mg orally, once daily
Experimental: Group 6 - Arm CLOSED; high mutation burden, POLE, POLD1	Drug: Nivolumab plus Ipilimumab; Combination Phase - 3mg/kg nivolumab administered as an intravenous infusion over 30 minutes every 3 weeks for the first 4 doses in combination with ipilmumab 1mg/kg administered intravenously over 30 minutes, followed by the single-agent phase.; Single-Agent Phase - 480mg nivolumab administered as an intravenous infusion over 30 minutes every 4 weeks.
Experimental: Group 7; BRCA1, BRCA2, mutations in HRD	Drug: Olaparib; 300mg taken twice daily
Experimental: Group 8; CDKN2A, CDK4, CCND1, SMARCA4	Drug: Palbociclib; 125mg orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days
Experimental: Group 9 Arm CLOSED; CSF1R, PDGFRA, PDGFRB,VEGFR1, VEGFR2, VEGFR3, KIT, FLT3, RET, FGFR1, FGFR2, FGFR3, VHL	Drug: Sunitinib; 50mg orally once daily on a schedule of 4 weeks on treatment followed by 2 weeks off
Experimental: Group 10; AKT1, AKT2, AKT3, FBXW7, FLCN, mTOR, NF1, NF2, NTRK3, PIK3CA, PIK3R1, PTEN, RHEB, STK11, TSC1, TSC2	Drug: Temsirolimus; 25mg infused over a 30-60 minute period once a week
Experimental: Group 11 - Arm CLOSED; ERBB2	Drug: Trastuzumab plus Pertuzumab; Trastuzumab = 3-weekly dose schedule. The recommended initial loading dose is 8mg/kg administered as a 90-minute infusion followed by 3-weekly maintenance dose of 6mg/kg administered as 90-minute infusion. Pertuzumab = 840mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by a dose of 420mg administered over a period of 30-60 minutes.
Experimental: Group 12; BRAFV600	Drug: Vemurafenib plus Cobimetinib; Vemurafenib = 960 mg orally every 12 hours. Cobimetinib = 60 mg orally once daily for 21 days, followed by 7 days of rest
Experimental: Group 13; PTCH1, SMO	Drug: Vismodegib; 150mg taken orally, once daily
Experimental: Group 14; ERBB2	Drug: Tucatinib; 300mg taken orally, twice daily

Outcome Measures

Primary Outcome Measures :

1. Objective response rate defined as the number of patients with complete response or partial response [ Time Frame: 4 years ]
   over the total number of patients in a given cohort.

Secondary Outcome Measures :

1. Number and severity of adverse events grade >3, or of lesser grade resulting in discontinuation, delay or reduction in dose of study drug [ Time Frame: 4 years ]
   measured by CTCAE
2. Progression-free survival by disease-appropriate objective criteria [ Time Frame: 4 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria: (screening step - non-drug specific)

• Adult (≥ 18 yrs) patient with a histologically-proven incurable metastatic solid tumour (excluding primary brain tumours), multiple myeloma or B cell non-Hodgkin lymphoma (excluding CLL, SLL and HCL), for whom there is no standard treatment known to prolong life, or who has refused such treatment.
• ECOG performance status 0-2.

• Patients must have normal organ function as follows:

  • Absolute neutrophil count: ≥ 1.5 x 10^9/L for solid tumours; ≥ 1.0 x 10^9/L for neurologic malignancies
  • Platelets ≥ 75 x 10^9/L (or ≥ 50 x 10^9/L if bone marrow involvement by myeloma or lymphoma).
  • Total bilirubin ≤ 1.5 x UNL.
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal value unless liver metastases are present in which case they must be < 5 x ULN;
  • Serum creatinine ≤ 1.5 x UNL or calculated or measured creatinine clearance ≥ 50mg/min/1.73µ^2
• Patients must have measurable disease
• Results must be available from tumour genomic or protein expression testing (if used to identify genetic variants), from one of the initiatives / groups listed in protocol Appendix VII. The test may have been performed on the primary tumour or a metastatic deposit (including bone marrow), or blood, in a diagnostic or research laboratory and must reveal a potentially actionable variant.
• Patient consent (Main Study Consent for the screening step) must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to the screening step to document their willingness to participate
• Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre or a CCTG IND site. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial.
• Women/men of childbearing potential must have agreed to use a highly effective contraceptive method.

Exclusion Criteria: (screening step - non-drug specific)

• Patients with prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Patients with ongoing toxicity ≥ CTCAE grade 2, other than peripheral neuropathy or asymptomatic, corrected biochemical toxicities (e.g. hypothyroidism corrected by thyroid replacement), related to prior anti-tumour treatment. Patients with ongoing peripheral neuropathy of ≥ CTCAE grade 3 will be excluded.
• Patients concurrently receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect (e.g. megestrol acetate, bisphosphonates) or ongoing castration-intent therapy for prostate cancer. These medications must have been started ≥ one month prior to enrollment on this study. Patients may be on warfarin, low molecular weight heparin or direct factor Xa inhibitors, unless such therapies are prohibited by drug-specific ineligibility criteria.
• Patients with known active progressive brain metastases. Patients with previously treated brain metastases are eligible, provided that the patient has not experienced a seizure or had a clinically significant change in neurological status within one month prior to screening. All patients with previously treated brain metastases must be stable (clinically and radiologically) for at least one month after completion of treatment and either off steroid treatment or only taking physiological doses of steroids prior to the screening step.
• Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure.
• Patients with known left ventricular ejection fraction (LVEF) < 40%.
• Patients with stroke (including TIA) or acute myocardial infarction within three months prior to the screening step.
• Patients with acute gastrointestinal bleeding within one month prior to the screening step.
• Patients with any other clinically significant medical condition which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness/social situations.
• Lactating and nursing women
• Patients who do not meet drug-specific eligibility requirements for the drug selected by the treating physician.

Contacts and Locations

Contacts

Contact: Janet Dancey; 613-533-6430; jdancey@ctg.queensu.ca

Locations

Canada, Alberta

Cross Cancer Institute; Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Contact: Quincy Chu 780 432-8248

Canada, British Columbia

BCCA - Cancer Centre for the Southern Interior; Suspended

Kelowna, British Columbia, Canada, V1Y 5L3

BCCA - Vancouver Cancer Centre; Recruiting

Vancouver, British Columbia, Canada, V5Z 4E6

Contact: Daniel John Renouf 604 877-6000 ext 672357

Canada, Ontario

Kingston Health Sciences Centre; Recruiting

Kingston, Ontario, Canada, K7L 2V7

Contact: Francisco Vera-Badillo 613 533-6430 ext 79893

London Regional Cancer Program; Recruiting

London, Ontario, Canada, N6A 5W9

Contact: Stephen Welch 519 685-8640

Ottawa Hospital Research Institute; Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Contact: John Hilton 613 737-7700 ext 75086

University Health Network; Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contact: Lillian Siu 416 946-2911

Canada, Quebec

The Jewish General Hospital; Recruiting

Montreal, Quebec, Canada, H3T 1E2

Contact: Petr Kavan 514 398-1444

Canada, Saskatchewan

Allan Blair Cancer Centre; Recruiting

Regina, Saskatchewan, Canada, S4T 7T1

Contact: Kimberly Hagel 306 766-2691

Saskatoon Cancer Centre; Recruiting

Saskatoon, Saskatchewan, Canada, S7N 4H4

Contact: Sunil K. Yadav 306 655-2710

Sponsors and Collaborators

Canadian Cancer Trials Group

AstraZeneca

Bristol-Myers Squibb

Hoffmann-La Roche

Pfizer

Seagen Inc.

Investigators

• Study Chair: Lillian Siu; Univ. Health Network-OCI/Princess Margaret Hospital, Toronto, ON Canada
• Study Chair: Daniel J Renouf; BCCA - Vancouver Cancer Centre, Vancouver BC, Canada

More Information

• Responsible Party: Canadian Cancer Trials Group
• ClinicalTrials.gov Identifier: NCT03297606
• Other Study ID Numbers: PM1; ESR-17-12831 ( Other Identifier: AstraZeneca ); CA209-9DL ( Other Identifier: Bristol-Myers Squibb ); ML39800 ( Other Identifier: Hoffmann-La Roche ); WI233446 ( Other Identifier: Pfizer )
• First Posted: September 29, 2017
• Last Update Posted: June 2, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• 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:

Multiple Myeloma; Lymphoma, Non-Hodgkin; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Lymphatic Diseases; Nivolumab; Trastuzumab; Ipilimumab; Pertuzumab; Sunitinib; Dasatinib; Olaparib; Palbociclib; Temsirolimus; Axitinib; Vemurafenib; Crizotinib; Tucatinib