Targeted Cancer Drugs for Cancer

(CAPTUR Trial)

Recruiting at 12 trial locations

Overseen By Janet Dancey

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Cytotoxic, Biologic, Radiation, Hormonal

Disqualifiers: Active brain metastases, Cardiac conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Variable, based on individual response

720 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on any other anti-cancer therapy, except for certain supportive care medications that may have an anti-cancer effect, which must have been started at least one month before joining the study.

What data supports the effectiveness of the drug Axitinib in cancer treatment?

Research shows that Axitinib, when combined with pembrolizumab, improved overall survival and progression-free survival in patients with metastatic renal cell carcinoma compared to sunitinib. This suggests that Axitinib can be effective in treating certain types of advanced kidney cancer. ^{1 2 3 4 5}

Is vismodegib generally safe for humans?

Vismodegib has been shown to have a generally tolerable safety profile in treating advanced basal cell carcinoma, although there are concerns about the potential development of another type of skin cancer, squamous cell carcinoma, in some patients. ^{6 7 8 9 10}

What makes the drug Axitinib unique for cancer treatment?

Axitinib is unique because it is a potent, selective inhibitor of specific proteins (vascular endothelial growth factor receptors 1, 2, and 3) that help tumors grow new blood vessels, making it effective in treating various solid tumors, including those resistant to previous therapies. It is taken orally and has shown promising results in several cancers, such as renal cell carcinoma and colorectal cancer, especially after other treatments have failed. ^{11 12 13 14 15}

Research Team

Lillian Siu

Principal Investigator

Univ. Health Network-OCI/Princess Margaret Hospital, Toronto, ON Canada

Daniel J Renouf

Principal Investigator

BCCA - Vancouver Cancer Centre, Vancouver BC, Canada

Eligibility Criteria

Adults with incurable metastatic solid tumors, multiple myeloma, or B cell non-Hodgkin lymphoma without standard life-prolonging treatment options. Participants must be over 18, have an ECOG performance status of 0-2, normal organ function and measurable disease. They should agree to use effective contraception and not have other conditions that could affect the trial's safety or results.

Inclusion Criteria

I can take care of myself and am up and about more than half of the day.

I am an adult with an incurable cancer (not brain cancer) and no life-prolonging treatment options or have refused them.

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, Patient consent (Main Study Consent for the screening step) must be appropriately obtained in accordance with applicable local and regulatory requirements, Patients must be accessible for treatment and follow-up, Women/men of childbearing potential must have agreed to use a highly effective contraceptive method

Exclusion Criteria

I do not have severe side effects from previous cancer treatments, except for manageable nerve pain or corrected thyroid issues.

I am not on any cancer treatments except for supportive care or ongoing hormone therapy for prostate cancer.

I have not had a stroke or heart attack in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive targeted therapy drugs specific to identified genetic changes in their cancer

Variable, based on individual response

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Treatment Details

Interventions

• Axitinib
• Bosutinib
• Crizotinib
• Dasatinib
• Erlotinib
• Nivolumab plus Ipilimumab
• Olaparib
• Palbociclib
• Sunitinib
• Temsirolimus
• Trastuzumab plus Pertuzumab
• Tucatinib
• Vemurafenib plus Cobimetinib
• Vismodegib

Trial Overview The CAPTUR study is testing targeted therapy drugs on patients with specific abnormal gene changes in their cancer. These therapies aim at the genetic level to block cancer growth and spread. The trial includes a variety of drugs like Erlotinib and Nivolumab plus Ipilimumab among others.

Participant Groups

Group I: Group 9 Arm CLOSED Experimental Treatment 1 Intervention

CSF1R, PDGFRA, PDGFRB,VEGFR1, VEGFR2, VEGFR3, KIT, FLT3, RET, FGFR1, FGFR2, FGFR3, VHL

Group II: Group 8 - Arm CLOSED Experimental Treatment 1 Intervention

CDKN2A, CDK4, CCND1, SMARCA4

Group III: Group 7 - Arm CLOSED Experimental Treatment 1 Intervention

BRCA1, BRCA2, mutations in HRD

Group IV: Group 6 - Arm CLOSED Experimental Treatment 1 Intervention

high mutation burden, POLE, POLD1

Group V: Group 5 - Arm CLOSED Experimental Treatment 1 Intervention

EGFR

Group VI: Group 4 - Arm CLOSED, no patients recruited Experimental Treatment 1 Intervention

KIT, PDGFRA, PDGFRB, ABL1

Group VII: Group 3 - Arm CLOSED Experimental Treatment 1 Intervention

ALK, ROS1, MET

Group VIII: Group 2 - Arm CLOSED, no patients recruited Experimental Treatment 1 Intervention

BCR-ABL, SRC

Group IX: Group 14 Experimental Treatment 1 Intervention

ERBB2

Group X: Group 13 - Arm CLOSED Experimental Treatment 1 Intervention

PTCH1, SMO

Group XI: Group 12 - Arm CLOSED Experimental Treatment 1 Intervention

BRAFV600

Group XII: Group 11 - Arm CLOSED Experimental Treatment 1 Intervention

ERBB2

Group XIII: Group 10 Arm CLOSED Experimental Treatment 1 Intervention

AKT1, AKT2, AKT3, FBXW7, FLCN, mTOR, NF1, NF2, NTRK3, PIK3CA, PIK3R1, PTEN, RHEB, STK11, TSC1, TSC2

Group XIV: Group 1 - Arm CLOSED, no patients recruited Experimental Treatment 1 Intervention

VEGFR1, VEGFR2, VEGFR3

Axitinib is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Inlyta for:

• Renal cell carcinoma

Approved in United States as Inlyta for:

• Advanced renal cell carcinoma

Approved in United Kingdom as Inlyta for:

• Advanced renal cell carcinoma

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Findings from Research

In a subgroup analysis of 94 Japanese patients with metastatic renal cell carcinoma, the combination of pembrolizumab and axitinib showed improved overall survival and progression-free survival compared to sunitinib, consistent with results from the larger global study.

The safety profile was also favorable, with fewer grade ≥3 treatment-related adverse events in the pembrolizumab-axitinib group (70%) compared to sunitinib (78%), and no deaths from treatment-related adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study. Tamada, S., Kondoh, C., Matsubara, N., et al.[2022]

Nivolumab-ipilimumab is the most cost-effective first-line treatment for metastatic clear-cell renal cell carcinoma (mRCC), with an incremental cost-effectiveness ratio (ICER) of $34,190 per quality-adjusted life year (QALY) compared to sunitinib.

In contrast, pembrolizumab-axitinib was found to be not cost-effective, with an ICER of $12,630,828 per QALY, and resulted in shorter QALY gains (1.99) compared to nivolumab-ipilimumab (3.23 QALY).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cost-effectiveness Analysis Comparing Pembrolizumab-Axitinib, Nivolumab-Ipilimumab, and Sunitinib for Treatment of Advanced Renal Cell Carcinoma. Chan, A., Dang, C., Wisniewski, J., et al.[2023]

In a study of 170 patients with advanced non-squamous non-small-cell lung cancer, axitinib combined with pemetrexed and cisplatin showed a higher objective response rate (45.5% and 39.7%) compared to chemotherapy alone (26.3%).

While the combination therapy did not significantly improve progression-free survival compared to chemotherapy alone, it was generally well tolerated, with hypertension being the most common serious side effect in the axitinib groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer. Belani, CP., Yamamoto, N., Bondarenko, IM., et al.[2021]

Axitinib shows significant long-term benefits for patients with metastatic renal cell carcinoma (mRCC), with long responders (LR) experiencing a median progression-free survival (PFS) of 18.1 months and overall survival (OS) of 36.0 months, based on a study of 157 patients.

Older age at treatment initiation and higher hemoglobin levels were identified as independent predictors for better outcomes with axitinib, suggesting that these factors can help clinicians identify patients who may benefit most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Factors Associated With Long-Term Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Axitinib: Real-World AXILONG Study. Pinto, Á., Reig, O., Iglesias, C., et al.[2022]

Recent advancements in antibody therapies, such as monoclonal antibodies and bispecific T cell engagers, have made cancer treatments more effective while reducing toxicity, enhancing the safety profile of these therapies.

The discovery of immune checkpoints like PD1 and PD-L1 has transformed cancer immunotherapy, allowing for the development of immune checkpoint inhibitors that can effectively treat previously hard-to-treat cancers, such as stage IV lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T "the living drugs", immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy. Liu, D.[2023]

In a long-term follow-up of the ERIVANCE BCC trial, vismodegib showed an investigator-assessed objective response rate of 48.5% in metastatic basal cell carcinoma (mBCC) and 60.3% in locally advanced BCC (laBCC), indicating its effectiveness in treating advanced forms of this skin cancer.

The treatment demonstrated a median duration of response of 14.8 months for mBCC and 26.2 months for laBCC, with manageable long-term safety, as adverse events were consistent with prior clinical experience and none of the reported deaths were related to vismodegib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. Sekulic, A., Migden, MR., Basset-Seguin, N., et al.[2020]

In a study involving 1215 patients with advanced basal cell carcinoma (BCC), vismodegib demonstrated a high tumor control rate, with a response rate of 68.5% for locally advanced BCC and 36.9% for metastatic BCC.

The safety profile of vismodegib was consistent with previous reports, with 98% of patients experiencing at least one treatment-emergent adverse event, but long-term exposure (up to 44 months) did not lead to increased severity or frequency of these adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial. Basset-Séguin, N., Hauschild, A., Kunstfeld, R., et al.[2018]

Vismodegib is the first oral treatment approved for basal cell carcinoma (BCC), showing response rates of 30% to 60% in patients with locally advanced or metastatic BCC who cannot undergo standard treatments like surgery or radiation.

Despite its efficacy, vismodegib has common side effects such as hair loss and muscle cramps, and its high cost of $7500 per month raises concerns about its overall value compared to standard therapies, which have higher cure rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vismodegib for the treatment of basal cell skin cancer. Poggi, L., Kolesar, JM.[2019]

In a study involving 1675 patients, treatment with vismodegib for basal cell carcinoma did not increase the risk of developing squamous cell carcinoma, showing an adjusted hazard ratio of 0.57, which suggests a lower risk compared to standard therapies.

The study indicates that factors like age, sex, and previous skin cancer history are more significant predictors for SCC development than vismodegib treatment itself, providing reassurance about the safety of this drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of cutaneous squamous cell carcinoma after treatment of basal cell carcinoma with vismodegib. Bhutani, T., Abrouk, M., Sima, CS., et al.[2017]

Vismodegib is a first-in-class hedgehog pathway inhibitor that effectively blocks the SMO protein, which is crucial for preventing inappropriate activation of the hedgehog signaling pathway linked to cancer.

Clinical trials, including a pivotal Phase II study, have shown that vismodegib is effective in treating advanced basal cell carcinoma with a generally tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vismodegib: a promising drug in the treatment of basal cell carcinomas. Dirix, L., Rutten, A.[2012]

Axitinib is an oral medication that inhibits key receptors involved in tumor growth and has shown activity against various solid tumors, including thyroid, pancreatic, lung, and breast cancers, based on Phase II trials.

While common side effects include fatigue and hypertension, axitinib was generally well tolerated, and larger randomized studies were underway to further evaluate its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. Choueiri, TK.[2018]

In a phase II trial involving 171 patients with metastatic colorectal cancer, axitinib did not show improved progression-free survival compared to bevacizumab when combined with standard chemotherapy regimens (FOLFOX or FOLFIRI).

Axitinib was associated with more grade ≥ 3 adverse events and treatment discontinuations due to side effects, indicating it may be less well tolerated than bevacizumab in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib or bevacizumab plus FOLFIRI or modified FOLFOX-6 after failure of first-line therapy for metastatic colorectal cancer: a randomized phase II study. Bendell, JC., Tournigand, C., Swieboda-Sadlej, A., et al.[2018]

Axitinib is an effective treatment for advanced renal cell carcinoma, functioning as a selective inhibitor of vascular endothelial growth factor receptors, with a recommended starting dose of 5 mg twice daily that can be adjusted based on patient tolerance.

The drug is rapidly absorbed and has a short plasma half-life, with pharmacokinetics showing dose-proportionality within the clinical range, and it is primarily metabolized in the liver, indicating a well-defined safety profile with minimal drug interactions at therapeutic doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacology of axitinib. Chen, Y., Tortorici, MA., Garrett, M., et al.[2021]

In a phase II study involving 38 chemotherapy-naïve patients with advanced squamous non-small-cell lung cancer, the combination of axitinib with cisplatin and gemcitabine showed promising anti-tumor activity, with a 36.8% partial response rate and a median overall survival of 14.2 months.

The treatment was generally well-tolerated, with a low rate of severe side effects; however, the study lacked a control group to definitively compare the efficacy of the combination therapy against standard chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of axitinib with doublet chemotherapy in patients with advanced squamous non-small-cell lung cancer. Bondarenko, IM., Ingrosso, A., Bycott, P., et al.[2022]

Axitinib is an effective second-line treatment for advanced renal cell carcinoma (RCC), showing significantly prolonged median progression-free survival compared to sorafenib in the phase III AXIS trial.

The tolerability profile of axitinib is manageable, with common side effects including diarrhea, hypertension, and fatigue, making it a viable option for patients who have already received other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib: a review in advanced renal cell carcinoma. Keating, GM.[2018]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A Cost-effectiveness Analysis Comparing Pembrolizumab-Axitinib, Nivolumab-Ipilimumab, and Sunitinib for Treatment of Advanced Renal Cell Carcinoma. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Clinical Factors Associated With Long-Term Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Axitinib: Real-World AXILONG Study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

CAR-T "the living drugs", immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Vismodegib for the treatment of basal cell skin cancer. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Risk of cutaneous squamous cell carcinoma after treatment of basal cell carcinoma with vismodegib. [2017]

10. England pubmed.ncbi.nlm.nih.gov

Vismodegib: a promising drug in the treatment of basal cell carcinomas. [2012]

11. England pubmed.ncbi.nlm.nih.gov

Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Axitinib or bevacizumab plus FOLFIRI or modified FOLFOX-6 after failure of first-line therapy for metastatic colorectal cancer: a randomized phase II study. [2018]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical pharmacology of axitinib. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Phase II study of axitinib with doublet chemotherapy in patients with advanced squamous non-small-cell lung cancer. [2022]

15. New Zealand pubmed.ncbi.nlm.nih.gov

Axitinib: a review in advanced renal cell carcinoma. [2018]