Phases of a Clinical Trial

Clinical trial treatments typically consist of several phases, with each phase focused on a different purpose. Most of the time, when you take part in a clinical trial, you will only be in that one phase of the study. Treatments move through the phases, but patients do not.

  • Phase I: Testing if a new treatment is safe. Doctors look for the best way to administer the treatment and for signs that cancer responds to the treatment 
  • Phase II: Testing if a specific type of cancer responds to the new treatment
  • Phase III: Testing if a new treatment is better than a standard cancer treatment
  • Phase IV: Examining long-term benefits and side effects

Phase I Trials

The goal of a Phase I trial is to determine the safety of the new treatment, learn the best way to administer the treatment (orally, intravenously, etc.) and to see whether or not the cancer responds.

Phase I trials usually include 15 to 30 patients, divided into small groups called cohorts. When the first cohort receives a dose of the new drug, doctors may collect blood or urine samples to measure the drug levels.

If no severe side effects present themselves, the next cohort will receive a higher dose of the same drug. This continues with each new cohort until the best dose is determined. With each increasing dose, doctors test each patient to see if he or she is responding to the protocol treatment. If the doctors find that the treatment is safe, then the trial will move forward to be studied in a Phase II trial.

The average length of a Phase I clinical trial can be relatively short due to it being an introductory phase.

Phase II Trials

Typically, a Phase II trial has less than 100 patients. While the main goal is to see if the treatment works, doctors still closely watch for side effects. If the new treatment works, doctors may go on to study it in a Phase III trial.

The average length of a Phase II clinical trial can range from less than a year to up to two years.

Phase III Trials

Phase III trials typically include a high number of patients. Hundreds or even thousands of patients around the country or world may participate. Patients enrolled in a Phase III clinical trial will be placed into one of the following groups:

  • Control group: this group receives the standard treatment
  • Study group: this group receives the new treatment being tested

Common questions patients have include:

How Are Patients Put Into Groups?

A computer program will randomly assign patients into groups. This helps to avoid bias in the clinical trial. (Bias happens when human choices affect a study’s results.)

Will My Doctor Know Which Group I’m In?

It depends on the trial. For a single blind study, patients do not know which group they are in, but their doctor does. For a double-blind study, neither the patient nor their doctors know which group the patient is in. (In case of an emergency, however, doctors can receive this information.)

Could I be Given a Placebo?

A placebo is something that looks like medicine but isn’t. If a placebo is used, it is administered along with the best standard treatment. Using a placebo allows doctors to compare standard treatment alone to standard treatment with a new drug. If there isn’t a standard treatment, then the placebo may be given alone, but this is uncommon.

After the Phase III trial, the FDA reviews the clinical trial results to make sure the treatment is safe and effective for people to use. The FDA decides whether to approve the treatment so that it is available for all patients.

The average length of a Phase III clinical trial can vary, ranging from one to four years or longer.

Phase IV Trials

In Phase IV trials, doctors study treatments that the FDA has already approved. The goal of Phase IV trials is to continue studying any side effects of a new treatment.

The average length of a Phase IV clinical trial is usually shorter than Phase III so typically fewer than four years.

Bladder Cancer

A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered Alone or in Combination with Atezolizumab to Subjects with Locally Advanced or Metastatic Solid Tumors (NCT03170960)
Principal Investigator: Dr. Jiaxin Niu 

A dose-escalation and dose-expansion study of enfortumab vedotin (ASG-22CE) in combination with pembrolizumab and/or chemotherapy for treatment of patients with locally advanced or metastatic urothelial cancer (NCT03288545
Principal Investigator: Santosh Rao

A Phase 3, Randomized, Double-blind Study to Compare the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Lenvatinib (E7080/MK-7902) Versus Pembrolizumab and Placebo as First Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma in Cisplatin-ineligible Participants Whose Tumors Express PD-L1, and in Participants Ineligible for Any Platinum-containing Chemotherapy Regardless of PD-L1 Expression (LEAP-011) (NCT03898180
Principal Investigator: Bryan Wong

An Open-label, Phase 1 Study of KHK2455 in Combination With Avelumab in Adult Subjects With Locally Advanced or Metastatic Urothelial Carcinoma (NCT03915405)
Principal Investigator: Santosh Rao

Feasibility Study of Motility Contrast Tomography for Predicting Therapeutic Response Among Bladder Cancer Patients Receiving Neoadjuvant Chemotherapy (NCT03739177)
Principal Investigator: Dr. Joseph Mashni 

An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors (NCT03767348)
Principal Investigator: Dr. Jiaxin Niu

A Phase III Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming with Intradermal BCG Before Intravesical Therapy for BCG‐Naïve High‐Grade Non‐Muscle Invasive Bladder Cancer (NCT03091660
Principal Investigator: Chinedu Mmeje

Kidney Cancer

Prostate Cancer

A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered Alone or in Combination with Atezolizumab to Subjects with Locally Advanced or Metastatic Solid Tumors (NCT03170960)
Principal Investigator: Dr. Jiaxin Niu 

Solid Tumor

A Phase 1b/2 Study of FT-2102 in Patients with Advanced Solid Tumors and Gliomas with an IDH1 Mutation (NCT03684811)
Principal Investigator: Dr. Madappa Kundranda

A Phase I/II Study of HB-201 Monotherapy or in Combination with Nivolumab in Patients with Human Papillomavirus 16 Positive (HPV 16+) Confirmed Cancers
Principal Investigator: Dr. Jiaxin Niu

A Phase 2, Non-randomized, Open Label, Single Arm, Multi-center Study Of Talazoparib For Neoadjuvant Treatment Of Germline Brca1/2 Mutation Patients With Early Triple-negative Breast Cancer(NCT03499353)
Principal Investigator: Dr. Lida Mina

A Phase I/II Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK525762 in Combination With Fulvestrant in Subjects With HR+/HER2- Advanced or Metastatic Breast Cancer (NCT02964507)
Principal Investigator: Dr. Shakeela Bahadur

A Phase 3, Multicenter, Randomized, Open-label, Active-controlled Study of DS-8201a, an Anti-HER2-antibody Drug Conjugate, Versus Treatment of Investigator's Choice for HER2-positive, Unresectable and/or Metastatic Breast Cancer Subjects Pretreated With Prior Standard of Care HER2 Therapies, Including T-DM1 (NCT03523585)
Principal Investigator: Dr. Lida Mina

A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered Alone or in Combination with Atezolizumab to Subjects with Locally Advanced or Metastatic Solid Tumors (NCT03170960)
Principal Investigator: Dr. Jiaxin Niu

A Phase 2 Study of ZEN003694 in Combination With Talazoparib in Patients With Triple-Negative Breast Cancer (NCT03901469)
Principal Investigator: Dr. Lida Mina

Phase 1/2 Dose-Escalation and Expansion Study of FLX475 Alone and in Combination With Pembrolizumab in Advanced Cancer (NCT03674567)
Principal Investigator: Tomislav Dragovich

A Randomized Phase III Clinical Trial Evaluating Post-Mastectomy Chestwall and Regional Nodal XRT and Post-Lumpectomy Regional Nodal XRT in Patients With Positive Axillary Nodes Before Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy (NCT01872975)
Principal Investigator: Dr. Emily Grade

Phase 1/1b Multicenter, Open-Label, First-in-Human Dose Escalation and Dose Expansion Study to Assess Safety and Tolerability of Orally Administered PMD-026 in Patients with Metastatic Breast Cancer with Expansion in Metastatic Triple Negative Breast Cancer (NCT04115306)
Principal Investigator: Dr. Lida Mina

Biliary Cancer

A Phase 3 Multicenter, Open-Label, Randomized, Controlled Study of Oral Infigratinib Versus Gemcitabine With Cisplatin in Subjects With Advanced/Metastatic or Inoperable Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations: The PROOF Trial (NCT03773302)  
Principal Investigator: Dr. Madappa Kundranda

A Phase 2, Multicenter, Open-label, Safety and Efficacy Study of XERMELO® (Telotristat Ethyl) plus First-line Chemotherapy in Patients with Locally Advanced, Unresectable, Recurrent or Metastatic Biliary Tract Cancer (BTC) (NCT03790111)
Principal Investigator: Boris Naraev

Colorectal Cancer

A randomized, multicenter, parallel-group, Phase III study to compare the efficacy of arfolitixorin versus leucovorin in combination with 5-fluorouracil, oxaliplatin, and bevacizumab in patients with advanced colorectal cancer (NCT03750786)
Principal Investigator: Dr. Madappa Kundranda

A Double Blind Placebo-Controlled Trial of Eflornithine and Sulindac to Prevent Recurrence of High Risk Adenomas and Second Primary Colorectal Cancers in Patients With Stage 0-III Colon or Rectal Cancer, Phase III - Preventing Adenomas of the Colon With Eflornithine and Sulindac (PACES) (NCT01349881)
Principal Investigator: Dr. Tomislav Dragovich 

A Phase II Clinical Trial Platform of Sensitization Utilizing Total Neoadjuvant Therapy (TNT) in Rectal Cancer (NCT02921256)
Principal Investigator: Dr.Gary Walker

Phase 1, Two-part (Dose Escalation, Dose Expansion), Multicenter, Non-randomized, Open-label, Multiple Dose, First-in-human Study of CA102N Monotherapy and of CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors (NCT03616574)
Principal Investigator: Dr. Tomislav Dragovich  
 

Gastric/GEJ

A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered Alone or in Combination with Atezolizumab to Subjects with Locally Advanced or Metastatic Solid Tumors (NCT03170960)
Principal Investigator: Jiaxin Niu

Phase 1/2 Dose-Escalation and Expansion Study of FLX475 Alone and in Combination With Pembrolizumab in Advanced Cancer (NCT03674567)
Principal Investigator: Dr. Tomislav Dragovich 

A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal And Genitourinary Tumors (NCT02599324)
Principal Investigator: Dr. Tomislav Dragovich 

Liver Cancer  

REFINE: Regorafenib Observational Study in Hepatocellular Carcinoma (NCT03289273)
Principal Investigator: Dr. Boris Naraev 

A Phase 1b/2 Study of FT-2102 in Patients with Advanced Solid Tumors and Gliomas with an IDH1 Mutation (NCT03684811)
Principal Investigator: Madappa Kundranda

A Phase 3 Double-blinded, Two-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) versus Placebo as Adjuvant Therapy in Participants with Hepatocellular Carcinoma and Complete Radiological Response after Surgical Resection or Local Ablation (KEYNOTE-937) (NCT03867084)
Principal Investigator: Madappa Kundranda

A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of MGD013, A Bispecific DART® Protein binding PD-1 and LAG-3 in Patients with Unresectable or Metastatic Neoplasms (NCT03219268)  
Principal Investigator: Shakeela Bahadur

Neuroendocrine Tumor

Pancreatic Cancer  

Pivotal, Randomized, Open-label Study of Tumor Treating Fields (TTFields, 150kHz) Concomitant With Gemcitabine and Nab-paclitaxel for Front-line Treatment of Locally-advanced Pancreatic Adenocarcinoma (NCT03377491)
Principal Investigator: Dr. Tomislav Dragovich

A Phase III Multicenter Open-Label Randomized Trial to Evaluate Efficacy and Safety of FOLFIRINOX (FFX) versus Combination of CPI-613 with modified FOLFIRINOX (mFFX) in Patients with Metastatic Adenocarcinoma of the Pancreas (NCT03504423)
Principal Investigator: Madappa Kundranda

A Phase II Study Evaluating Bi-weekly Dosing of Gemcitabine Plus nab-Paclitaxel In The First Line Treatment Metastatic Pancreatic Cancer In Older Adults ( >70 years old)  
Principal Investigator: Madappa Kundranda

Solid Tumor

A Phase 1 Study of BOS172738 in Patients with Advanced Solid Tumors with RET Gene Alterations including Non-Small Cell Lung Cancer (NSCLC) and Medullary Thyroid Cancer (MTC) (NCT03780517)
Principal Investigator: Dr. Jiaxin Niu

A Phase 1b/2 Study of FT-2102 in Patients with Advanced Solid Tumors and Gliomas with an IDH1 Mutation (NCT03684811
Principal Investigator: Madappa Kundranda

An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors (NCT03767348
Principal Investigator: Dr. Jiaxin Niu

A Phase 1/2 Study of Combination Immunotherapy and mRNA Vaccine in Subjects with Nonsmall Cell Lung Cancer (NSCLC) (NCT03164772)
Principal Investigator: Dr. Jiaxin Niu

A Multicenter, Two-Part, Phase 2 Clinical Study of CMP-001 in Combination with atezolizumab with and without radiation therapy in Subjects with Advanced Non-Small Cell Lung Cancer (NSCLC) (NCT03438318)
Principal Investigator: Dr. Jiaxin Niu

A Phase III, Randomized, Double-blind Trial of Platinum Doublet Chemotherapy +/-Pembrolizumab (MK-3475) as Neoadjuvant/Adjuvant Therapy for Participants with Resectable Stage IIB or IIIA Non-small Cell Lung Cancer (NSCLC) (KEYNOTE-671) (NCT03425643)
Principal Investigator: Dr. Qing Zhao

A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered Alone or in Combination with Atezolizumab to Subjects with Locally Advanced or Metastatic Solid Tumors (NCT03170960)
Principal Investigator: Dr. Jiaxin Niu

A Phase 1/2 Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of the Oral EGFR/HER2 Inhibitor TAK-788 (AP32788) in Non-Small Cell Lung Cancer (NCT02716116)
Principal Investigator: Dr. Jiaxin Niu

A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of MGD013, A Bispecific DART® Protein binding PD-1 and LAG-3 in Patients with Unresectable or Metastatic Neoplasms (NCT03219268)
Principal Investigator: Shakeela Bahadur

Phase 1/2 Dose-Escalation and Expansion Study of FLX475 Alone and in Combination With Pembrolizumab in Advanced Cancer (NCT03674567)
Principal Investigator: Tomislav Dragovich

An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors (NCT03767348)
Principal Investigator: Dr. Jiaxin Niu

A Phase 1b/2 Study of FT-2102 in Patients with Advanced Solid Tumors and Gliomas with an IDH1 Mutation (NCT03684811)
Principal Investigator: Madappa Kundranda

An Observational Registry Study to Evaluate the Performance of the BDX-XL2 Test (NCT03766958)
Principal Investigator: Dr. Archan Shah

A Phase 1 Study of BOS172738 in Patients with Advanced Solid Tumors with RET Gene Alterations including Non-Small Cell Lung Cancer (NSCLC) and Medullary Thyroid Cancer (MTC) (NCT03780517)
Principal Investigator: Dr. Jiaxin Niu

A Phase 1/2A Open-Label, Multi-Dose, Multi-Center Escalation and Exploratory Study of Cerdulatinib (PRT062070) in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) or B Cell or T Cell Non-Hodgkin Lymphoma (NHL) (NCT01994382)
Principal Investigator: Dr. Javier Munoz  

A Phase 2 Study of Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy in Adult Patients With Aggressive B-cell NHL (017006) (NCT03483103)
Principal Investigator: Dr. Javier Munoz (Please note: The study recruitment for this study are currently on hold)

A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL) (NCT03105336)
Principal Investigator: Dr. Javier Munoz

A Phase Ib/II, Open-Label, Multicenter, Randomized, Controlled Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Patients With B-Cell Non-Hodgkin Lymphoma (NCT03677141)
Principal Investigator: Dr. Javier Munoz

An Open-Label, Phase 1 Safety and Phase 2 Randomized Study of JCAR017 in Subjects with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (017004)(NCT03331198)
Principal Investigator: Dr. Javier Munoz 

A Phase 2 Multicenter Study Evaluating the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Subjects With High-Risk Large B-Cell Lymphoma (ZUMA-12) (NCT03761056)
Principal Investigator: Dr. Javier Munoz

A Phase 1/Phase 2 Clinical Study to Evaluate the Safety and Efficacy of a Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants with Hematologic Malignancies (NCT03598608)
Principal Investigator: Dr. Javier Munoz

Phase 1, Multicenter, Open-Label Study of the Antibody-Drug Conjugate TRPH-222 in Subjects With Relapsed and/or Refractory B-Cell Lymphoma (NCT03682796)  
Principal Investigator: Dr. Javier Munoz

A Phase 1/Phase 2 Clinical Study to Evaluate the Safety and Efficacy of a Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants with Hematologic Malignancies (NCT03598608)
Principal Investigator: Dr. Javier Munoz

A Phase 2 Study of Daratumumab Subcutaneous (Dara-SC) Administration in Combination With Carfilzomib and Dexamethasone (DKd) Compared With Carfilzomib and Dexamethasone (Kd) in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab Intravenous (Dara-IV) to Evaluate Daratumumab Retreatment (NCT03871829)
Principal Investigator: Sumit Madan

A Single-Arm, Open-Label, Phase 1 Study of the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-715 to Evaluate an Anti-BCMA Allogeneic CAR T Cell Therapy in Subjects With Relapsed/Refractory Multiple Myeloma (NCT04093596
Principal Investigator: Rajneesh Nath

Breast Cancer

A Randomized Phase III Clinical Trial Evaluating Post-Mastectomy Chestwall and Regional Nodal XRT and Post-Lumpectomy Regional Nodal XRT in Patients With Positive Axillary Nodes Before Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy (NCT1872975)
Principal Investigator: Dr.Emily Grade

Bone Metastases

A randomized trial evaluating rapid delivery of dose escalated hypofractionated radiotherapy for patients diagnosed with bone metastases for effective palliation of
symptoms
 (NCT02163226)
Principal Investigator: Dr.Gary Walker 

Head and Neck Cancer

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of the Superoxide Dismutase Mimetic GC4419 to Reduce Severe Oral Mucositis (SOM) Associated with Chemoradiotherapy for Locally Advanced, Non-Metastatic Head and Neck Cancer (NCT03689712)
Principal Investigator: Dr.Gary Walker

Prostate Cancer

Prospective Data Registry and Quality of Life Assessment of Men Undergoing High Dose Rate Brachytherapy of the Prostate Using Real-Time Ultrasound Planning 
Principal Investigator: Dr. Anna Likhacheva

Prospective Evaluation of Men Undergoing Stereotactic Body Radiation Therapy (SBRT) for Prostate Cancer
Principal Investigator: Dr. Rachit Kumar

Rectal Cancer

A Phase II Clinical Trial Platform of Sensitization Utilizing Total Neoadjuvant Therapy (TNT) in Rectal Cancer (NCT02921256)
Principal Investigator: Dr.Gary Walker

Skin Cancer

Skin Surface Brachytherapy for Non-Melanoma Skin Cancers: Prospective Data Registry and Quality of Life Assessment
Principal Investigator: Dr.Emily Grade

Solid Tumor

EXTernal beam radiation to Eliminate Nominal metastatic Disease (EXTEND): A randomized phase II basket trial assessing the efficacy of upfront local consolidative therapy (LCT) for oligometastatic disease (NCT03599765)
Principal Investigator: Dr.Gary Walker