Clinical Trials: Past Studies
Over the past two decades, about 20 Phase II clinical trials were designed specifically for ACC patients or for salivary gland cancer patients with a large group of ACC patients. These trials are listed in the table below. It is not an exhaustive list as it excludes some smaller studies with fewer than 9 ACC patients as well as some privately-funded studies that were not published. Chemical names are used for each compound with trade names included in parentheses. Hyperlinks provide general descriptions of the drugs as well as published articles or abstracts on each study.
Completed Phase II Clinical Trials with ACC Patients
Compound Target(s) Institution ACC Patients Objective Response Stable Disease Clinial Benefit Progression Required? Publication Year Link Sunitinib (Sutent) PDGFR, VEGFR, CKIT, RET Princess Margaret Hospital 13 0% 85% 62% Yes 2011 View Cetuximab (Erbitux) EGFR Istituto Nazionale dei Tumori 23 0% 87% 52% 2009 View Gemcitabine & Cisplatin Chemotherapy NCI Canada 10 20% NA 2009 View Gemcitabine Chemotherapy Radboud University Nijmegen 21 0% 52% 48% 2008 View Lapatinib (Tykerb) EGFR, HER2 Princess Margaret Hospital 19 0% 79% 47% Yes 2007 View Bortezomib (Velcade) NFKB, 26S Proteasome University of Pittsburgh/ECOG 25 0% 64% Yes 2006 View Gefitinib (Iressa) EGRF MD Anderson 19 0% 68% Yes 2005 View Imatinib & Cisplatin ABL, CKIT, PDGFR Christie Hospital NHS Trust 28 11% 68% Yes 2011 View Imatinib (Gleevec) ABL, CKIT, PDGFR Tel Aviv University 10 0% 70% 2007 View Imatinib (Gleevec) ABL, CKIT, PDGFR Princess Margaret Hospital 15 0% 56% 2005 View Paclitaxel Chemotherapy LSU/ECOG 13 0% 54% 2006 View Paclitaxel & Carboplatin Chemotherapy University of Torino 10 20% NA Yes 2000 View Vinorelbine & Cisplatin Chemotherapy University of Torino 9 44% NA Yes 2001 View Vinorelbine Chemotherapy University of Torino 13 15% NA Yes 2001 View Epirubicin Chemotherapy Free University Hospital (NL) 20 10% 50% Yes 1993 View Cisplatin & 5-FU Chemotherapy Royal Marsden NHS Trust 11 0% 55% 1997 View Cisplatin & Doxorubicin & Cyclophosphamide Chemotherapy Istituto Nazionale dei Tumori 12 25% 42% Yes 1996 View Cisplatin & Doxorubicin & Bleomycin Chemotherapy Radboud University Nijmegen 9 33% 55% 1992 View Cisplatin Chemotherapy Radboud University Nijmegen 10 0% 50% 1992 View Cisplatin Chemotherapy Istituto Nazionale dei Tumori 13 15% 46% 1991 View Mitoxantrone Chemotherapy Rotterdam Cancer Institute 32 12% 69% 1996 View Mitoxantrone Chemotherapy Johns Hopkins 18 6% 67% 1990 View Download Completed Phase II Clinical Trials with ACC Patients
In reviewing the history of Phase II clinical trials in ACC, it is important to take note of two key factors:
- Progression Requirements – Did the clinical trial require ACC patients to have documented progression (tumor growth greater than 20%) prior to starting therapy? ACC patients with metastases may have long periods of stable disease, making it difficult to determine whether stable disease was the result of the drug. Clinical trials that require progression give a better indication of the drug’s effectiveness.
- Clinical Benefit – Did the patient have an objective response (tumor shrinkage of at least 30%) or stable disease, either of which lasted longer than 6 months? Sometimes patients have rapid tumor shrinkage that qualifies as an objective response, but then there is a rapid reversal and progression. Or a slow-growing ACC tumor, unaffected by the drug, may take 3 months to reach 20% growth; the patient will be classified as having stable disease despite the drug’s lack of efficacy. By using a longer horizon, this metric attempts to measure meaningful patient benefit.
Patients should keep in mind that objective responses and stable disease are measures of tumor volume, not overall survival. It is reasonable to assume that smaller tumors mean a longer lifespan, but it is not always the case. Once a treatment stops being effective, tumors may grow back more quickly. Patients must weigh the potential side effects of any treatment against the possibility of extended survival and reduced pain from tumor shrinkage.
The broad conclusion to be drawn from the history of clinical trials with ACC patients is that some standard chemotherapies produce objective responses or clinical benefit in small subsets of ACC patients, but none have been shown to have broad effectiveness, long durations of response or an impact on survival. ACCRF’s affiliated researchers are working hard to come up with very effective therapies and a cure for ACC. In the meantime, however, there is a dire need for drugs that can delay progression. A good starting point is to focus on those clinical trials that had disease progression as an eligibility criterion and had high rates of clinical benefit:
- Sunitinib – 8 of 13 progressing patients (62%) had stable disease for more than 6 months.
- Lapatinib – 10 of 19 progressing patients (47%) had stable disease for more than 6 months.
- Vinorelbine & Cisplatin – 4 of 9 progressing patients (44%) had objective responses of undisclosed length.
Progressing ACC patients without access to clinical trials may wish to discuss these results with their physicians. In addition, they should keep in mind the promising Phase I results of Vorinostat as the ACC community awaits the Phase II results.
Patients enrolling in clinical trials perform an incredibly honorable service for the entire patient community. Without them, it would not be possible to determine systematically whether a particular treatment is effective or safe. Even clinical trials that show that a drug is ineffective are incredibly valuable as future patients are spared the unnecessary side effects and try more promising drugs. Some physicians prescribe approved cancer drugs “off-label” (i.e., approved for tumor types different from the treated tumor) to their patients who cannot travel to or do not qualify for a clinical trial. Unfortunately, those results are not tabulated and shared with others as is the case with clinical trials. Without a doubt, current ACC patients owe a debt of gratitude to those who have helped guide our current understanding of how ACC responds to systemic therapies.
For more background and details on clinical trials, please read ACCRF’s Guide to Systemic Therapy for Patients With Progressive ACC.