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

• ClinicalTrials.gov Identifier: NCT03297606
• Recruitment Status: Recruiting
• First Posted: September 29, 2017
• Last Update Posted: April 29, 2024
• 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

Tracking Information

• First Submitted Date: September 27, 2017
• First Posted Date: September 29, 2017
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: March 23, 2018
• Estimated Primary Completion Date: January 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 21, 2019)

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.

Original Primary Outcome Measures (submitted: September 28, 2017)

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 the given tumour type cohort.

Current Secondary Outcome Measures (submitted: June 21, 2019)

• 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
• Progression-free survival by disease-appropriate objective criteria [ Time Frame: 4 years ]

Original Secondary Outcome Measures (submitted: September 28, 2017)

• Number and severity of adverse events [ Time Frame: 4 years ]
  measured by CTCAE
• Progression-free survival confirmed by disease-appropriate objective criteria [ Time Frame: 4 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
• Official Title: Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR): A Phase II Basket Trial
• 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.
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Advanced Solid Tumors

Intervention

• Drug: Olaparib
  300mg taken twice daily
• Drug: Dasatinib
  100mg administered orally once daily
• 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.
• Drug: Axitinib
  5mg orally twice daily
• Drug: Bosutinib
  500mg orally once daily
• Drug: Crizotinib
  250mg orally twice daily
• Drug: Palbociclib
  125mg orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days
• Drug: Sunitinib
  50mg orally once daily on a schedule of 4 weeks on treatment followed by 2 weeks off
• Drug: Temsirolimus
  25mg infused over a 30-60 minute period once a week
• Drug: Erlotinib
  150mg orally, once daily
• 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.

• 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

• Drug: Vismodegib
  150mg taken orally, once daily
• Drug: Tucatinib
  300mg taken orally, twice daily

Study Arms

• Experimental: Group 1 - Arm CLOSED, no patients recruited
  VEGFR1, VEGFR2, VEGFR3
  Intervention: Drug: Axitinib
• Experimental: Group 2 - Arm CLOSED, no patients recruited
  BCR-ABL, SRC
  Intervention: Drug: Bosutinib
• Experimental: Group 3 - Arm CLOSED
  ALK, ROS1, MET
  Intervention: Drug: Crizotinib
• Experimental: Group 4 - Arm CLOSED, no patients recruited
  KIT, PDGFRA, PDGFRB, ABL1
  Intervention: Drug: Dasatinib
• Experimental: Group 5 - Arm CLOSED
  EGFR
  Intervention: Drug: Erlotinib
• Experimental: Group 6 - Arm CLOSED
  high mutation burden, POLE, POLD1
  Intervention: Drug: Nivolumab plus Ipilimumab
• Experimental: Group 7 - Arm CLOSED
  BRCA1, BRCA2, mutations in HRD
  Intervention: Drug: Olaparib
• Experimental: Group 8 - Arm CLOSED
  CDKN2A, CDK4, CCND1, SMARCA4
  Intervention: Drug: Palbociclib
• Experimental: Group 9 Arm CLOSED
  CSF1R, PDGFRA, PDGFRB,VEGFR1, VEGFR2, VEGFR3, KIT, FLT3, RET, FGFR1, FGFR2, FGFR3, VHL
  Intervention: Drug: Sunitinib
• Experimental: Group 10 Arm CLOSED
  AKT1, AKT2, AKT3, FBXW7, FLCN, mTOR, NF1, NF2, NTRK3, PIK3CA, PIK3R1, PTEN, RHEB, STK11, TSC1, TSC2
  Intervention: Drug: Temsirolimus
• Experimental: Group 11 - Arm CLOSED
  ERBB2
  Intervention: Drug: Trastuzumab plus Pertuzumab
• Experimental: Group 12 - Arm CLOSED
  BRAFV600
  Intervention: Drug: Vemurafenib plus Cobimetinib
• Experimental: Group 13 - Arm CLOSED
  PTCH1, SMO
  Intervention: Drug: Vismodegib
• Experimental: Group 14
  ERBB2
  Intervention: Drug: Tucatinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 28, 2017): 720
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 31, 2027
• Estimated Primary Completion Date: January 31, 2026 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Canada

Administrative Information

• NCT Number: 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 )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Canadian Cancer Trials Group
• Original Responsible Party: Same as current
• Current Study Sponsor: Canadian Cancer Trials Group
• Original Study Sponsor: Same as current

Collaborators

• 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

• PRS Account: Canadian Cancer Trials Group
• Verification Date: April 2024