Early Phase Clinical Trials - Developmental Therapeutics

The Developmental Therapeutics Program at Penn Medicine’s Abramson Cancer Center is dedicated to the study of promising new drugs, or combination of drugs in treating cancer. Over the last decade, many people with cancer have witnessed the success of these studies that have helped improve and increase treatment options. The hope is that these new drugs will broaden the treatment options available to all cancer patients while improving care and quality of life.

It is only through research that we can continue to offer a better outlook for a cure.

The Developmental Therapeutics Program tests these new drugs by conducting Phase I and II clinical trials. Clinical trials are studies to determine the effectiveness of new ways to prevent, detect and treat cancer. The purpose of each clinical trial is to answer a specific question.

Phase I and II Clinical Trials

Phase I Trials

Phase I trials are the first step in testing a new treatment in humans. The major intent of Phase I studies is to establish how a particular treatment will act and the safety limits of the treatment. In these studies, researchers look for the best way to give a new treatment -- such as by mouth, or injection -- and how frequently it should be given. They also try to find out the best dose that can be given safely.

In order to do this; the treatment is given to small groups of patients in increasing dosages, and often by different routes. Patients are carefully watched for harmful side effects. Usually one group receives one dosage; another receives a different dosage. This process continues in order to find out the highest dose that does not cause harmful side effects. At the end of Phase I trials, it is generally known which doses are safe and how best to deliver the treatment.

Because less is known about the possible risks and benefits in Phase I trials, these studies usually include only a small number of patients who would not be helped by other known treatments. Tumor shrinkage or stabilization is an important goal of therapy but usually occurs only in a small number of patients. In some cases the treatment may be administered at a dosage that is too low to be effective, or the treatment may be ineffective at any dose.

Phase II Trials

Phase II trials continue to test the safety of the drug and begin to evaluate how well the new drug works. Phase II studies usually focus on a particular type of cancer. These trials work on learning whether the new treatment works--such as: does it shrink a tumor? As in Phase I, only a small number of people take part because of the risks and unknowns involved.

In order for Phase II trials to determine which particular cancer responds to a treatment, studies are done in a group of patients with the same type of cancer. To participate in Phase II trials, people with cancer usually must have what is called "measurable disease." This means that there is at least one tumor present that can be seen on physical examination or a study, such as an x-ray, CT or MRI scan.

In Phase II trials the tumor size is measured and tracked to see the response to treatment:

Usually, if measurable disease decreases by at least 50%, it is believed that the cancer has responded to treatment.

If no detectable tumor remains, it is said that the treatment has led to a "complete response" or CR.

Tumors that have shrunk more than 50% but still remain mean that a "partial response" or PR has taken place.

  • While encouraging, neither a complete response nor a partial response means that a cure has taken place. There is always a risk that the cancer can return. The length of time before a cancer returns can vary from patient to patient and treatment to treatment. Some new treatments can result in responses that last years, whereas many produce responses that last months.

How Clinical Trials are Carried Out

In clinical trials, both research and patient well-being are important. Research with people is carried out according to strict scientific and ethical principles. These include:

  • Each clinical trial has a protocol (action plan) explaining how it will be carried out.
  • The person in charge of the study is called the investigator. This is usually a doctor. The investigator prepares the protocol for the study. This protocol explains what will be done in the study and why. It outlines how many people will take part in the study, what medical tests they will receive and how often, and the treatment plan. The same protocol is used by each doctor that takes part in the study.
  • For patient safety, each protocol is approved by:
  • The organization that sponsors the study (such as the National Cancer Institute or American Cancer Society).
  • Penn's Institutional Review Board, (IRB). This board, which includes consumers, clergy, and health professionals reviews the protocol to ensure that the research will not expose patients to extreme or unethical risks.
  • The Cancer Center's Clinical Trials and Scientific Review and Monitoring Committee, which is approved by the National Cancer Institute and reviews the scientific merit of a clinical trial before it begins.
  • Each study enrolls people who are alike in key ways. Each study's protocol describes the characteristics that all patients in the study must have. These key characteristics are called eligibility criteria. Eligibility criteria differ from study to study, depending on the research purpose. They may include such factors as age, gender, the type and stage of cancer.

Determining Eligibility to Participate

Each trial has specific eligibility requirements. Not everyone is an appropriate candidate for a Phase I or II study. The most important thing is whether the trial is the best treatment option at the time. If better treatment options exist, or the risk of side effects is too high, other approaches should be pursued.

To find out if you are eligible for a particular Phase I or II trial, please consult the Cancer Center's clinical trials matching service on OncoLink.

Generally, you must meet the following criteria to be eligible:

  • Solid tumors (phase I or II trials are not usually offered to people with hematologic malignancies like leukemia)
  • Good performance status; this means that you can carry out your daily activities fairly well
  • Relatively normal laboratory values
  • No active brain metastases
  • No serious current illness

If you are under consideration for hospice and other forms of terminal care, you may not be a candidate for a phase I or II trial.

How to Enroll in a Clinical Trial in the Developmental Therapeutics Program

If you are eligible for a Phase I or II trial you will meet with a physician on the research team. The physician you see varies, depending on your type of cancer. During this visit, you will receive information on the different options available to you and specific recommendations about which trial may be appropriate for you.

If the physician recommends enrolling in a trial, the next step is to go home and think about what you have discussed. You will have received a consent form during your visit. You should read this in detail at home. After taking time to think about all the information you've been given, you will have the chance to meet with a nurse specialist who will provide additional information and discuss any concerns and questions you may have.

In some cases, enrolling in a trial is not the best approach. In such cases the physician will recommend that you not take part in the trial.

Current Investigations by the Developmental Therapeutics Program

Penn Medicine’s Developmental Therapeutics Program is a highly interactive group of investigators from multiple clinical and basic science departments. Program members are responsible for the development and conduct of trials in a particular field with an emphasis on innovative treatment approaches.

The experimental therapeutics research project team evaluates novel therapies in well-designed, hypothesis-driven, Phase I and Phase II studies for a range of cancers. The Developmental Therapeutics Program is pursuing studies of novel and targeted agents with endpoints that include clinical effects, pharmacokinetics, MRI studies of blood flow, pharmacogenetics, gene expression, and pharmacogenomics. With the help of a recently awarded Phase II contract, studies are underway in head and neck cancer, colon cancer, melanoma, non-small cell lung cancer and an array of targeted therapies. Among the agents under investigation in Phase I and II trials are epothilones, novel taxanes, novel platinum compounds, anti-vascular and anti-angiogenic agents, kinase inhibitors, and PPAR-gamma agonists. Pharmacodynamic studies of novel agents round out the developmental focus of the group.