A Phase 1 Study of Durvalumab, Tremelimumab and Radiotherapy in Recurrent Gynecologic Cancer
Overview
- Phase
- Phase 1
- Intervention
- Durvalumab
- Conditions
- Recurrent Gynecological Cancer
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 16
- Locations
- 2
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of Radiotherapy with durvalumab and tremelimumab
- Status
- Terminated
- Last Updated
- 11 months ago
Overview
Brief Summary
This research study is evaluating the safety and effectiveness of 2 immunotherapy drugs in combination with radiation therapy as a possible treatment for recurrent or metastatic gynecologic cancer.
The names of the immunotherapy drugs involved in this study are:
- Durvalumab
- Tremelimumab
Detailed Description
This research study is a Phase I clinical trial, which tests the safety of an investigational drug or drugs and also tries to define the appropriate dose and combination of the investigational drugs to use for further studies. "Investigational" means that the drugs are being studied but have not been approved by the FDA (the U.S. Food and Drug Administration). In this study, the combination of durvalumab and tremelimumab is considered to be investigational and as such has not been approved for this or any cancer. -- Durvalumab and tremelimumab are immunotherapy drugs that may stop cancer cells from growing by activating the immune system. The immune system is one of the body's natural defenses against the growth of cancer cells. AstraZeneca has evaluated the effectiveness and side effects of both durvalumab and tremelimumab individually for many cancer types, including lung, head and neck cancer, and melanoma. These types of immunotherapy drugs are also being studied in ovarian, endometrial and cervical cancer. In addition, AstraZeneca has studied the combination of durvalumab and tremelimumab in participants with lung and pancreatic cancers. Based on these studies, AstraZeneca has determined the dosing, schedule and expected side effects for the 2 study drugs when delivered together. In women with recurrent or metastatic gynecologic cancer, radiation therapy is often used to help with symptoms, such as bleeding, pain or swelling. Clinical reports have shown that radiation treatment can increase the body's response to an immunotherapy drug against tumors both within and outside the radiation field. This study is the first in which the combination of durvalumab, tremelimumab and abdominal or pelvic radiation is given to humans. The investigators hope that this combination with radiation will lead to a better treatment response to the immunotherapy drugs. The investigators will also look to see if participants whose tumors contain a particular genetic make-up have a better response to immunotherapy and radiation treatment.
Investigators
Martin King, MD, PhD
Principal Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •Ability to understand and the willingness to sign a written informed consent document. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- •Participants must have histologically or cytologically confirmed endometrial, ovarian (including ovarian epithelial, fallopian tube, primary peritoneal), cervical, vaginal, or vulvar cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- •Participants must have measurable disease, defined as at least 1 lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥20 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease. See also 3.1.10 as all measurable/target lesions must not be located within the planned radiation field for the expansion cohort.
- •Patients must have progressive disease following prior therapy. Specifically, patients must have progressed on platinum-based chemotherapy.
- •At least 21 days must have elapsed from prior therapy (chemotherapy or radiation).
- •Age of 18 years or older. Because no dosing or adverse event data are currently available on the use of durvalumab in combination with tremelimumab and radiation in patients \<18 years of age, children are excluded from this study.
- •ECOG performance status ≤1 (Karnofsky ≥60%, see Appendix A).
- •Body weight of greater than 30 kg.
- •Participants must have normal organ and marrow function as defined below:
- •Hgb \>=9g/dl
Exclusion Criteria
- Not provided
Arms & Interventions
Phase I Safety Lead-In
A modified 3+3 design will be used in this trial Lead-in phase with Durvalumab\* and radiation therapy \*q4 weeks durvalumab for 13 cycles or until progression
Intervention: Durvalumab
Phase I Safety Lead-In
A modified 3+3 design will be used in this trial Lead-in phase with Durvalumab\* and radiation therapy \*q4 weeks durvalumab for 13 cycles or until progression
Intervention: Radiation Therapy
Phase I Radiation Dose Evaluation
* Durvalumab * Tremelimumab\* -- Start radiation dose from safety lead-in (level 0 or level -1) \*q4 weeks durvalumab / tremelimumab for 4 cycles and continue durvalumab for 13 cycles or until disease progression
Intervention: Durvalumab
Phase I Radiation Dose Evaluation
* Durvalumab * Tremelimumab\* -- Start radiation dose from safety lead-in (level 0 or level -1) \*q4 weeks durvalumab / tremelimumab for 4 cycles and continue durvalumab for 13 cycles or until disease progression
Intervention: Tremelimumab
Phase I Radiation Dose Evaluation
* Durvalumab * Tremelimumab\* -- Start radiation dose from safety lead-in (level 0 or level -1) \*q4 weeks durvalumab / tremelimumab for 4 cycles and continue durvalumab for 13 cycles or until disease progression
Intervention: Radiation Therapy
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) of Radiotherapy with durvalumab and tremelimumab
Time Frame: 8 Weeks
Incidence of dose-limiting toxicities for each dose level or regimen
Secondary Outcomes
- Local Control Rate(Baseline to 6 months, 12 Months)
- Overall Survival Rate(Baseline to 6 months, 12 Months)
- Abscopal Response Rate(One Year)
- Local Response Rate(One Year)
- Overall Response Rate(One Year)
- Progression Free Survival Rate(Baseline to 6 months, 12 Months)
- Response Duration(One Year)